document_title: Fatty acid metabolism

question_text: where do fatty acids enter the krebs cycle

text: Fatty acid metabolism

text: Fatty acid catabolism[edit]

text: Fatty acids are released, between meals, from the fat depots in adipose tissue, where they are stored as triglycerides, as follows:

text:
Lipolysis, the removal of the fatty acid chains from the glycerol to which they are bound in their storage form as triglycerides (or fats), is carried out by lipases. These lipases are activated by high epinephrine and glucagon levels in the blood (or norepinephrine secreted by sympathetic nerves in adipose tissue), caused by declining blood glucose levels after meals, which simultaneously lowers the insulin level in the blood.[1]
Once freed from glycerol, the free fatty acids enter the blood, which transports them, attached to plasma albumin, throughout the body.[4]
Long chain free fatty acids enter the metabolizing cells (i.e. most living cells in the body except red blood cells and neurons in the central nervous system) through specific transport proteins, such as the SLC27 family fatty acid transport protein.[5][6] Red blood cells do not contain mitochondria and are therefore incapable of metabolizing fatty acids; the tissues of the central nervous system cannot use fatty acids, despite containing mitochondria, because long chain fatty acids (as opposed to medium chain fatty acids[7][8]) cannot cross the blood brain barrier[9] into the interstitial fluids that bathe these cells.
Once inside the cell long-chain-fatty-acid—CoA ligase catalyzes the reaction between a fatty acid molecule with ATP (which is broken down to AMP and inorganic pyrophosphate) to give a fatty acyl-adenylate, which then reacts with free coenzyme A to give a fatty acyl-CoA molecule.
In order for the acyl-CoA to enter the mitochondrion the carnitine shuttle is used:[10][11][12]

text:
Acyl-CoA is transferred to the hydroxyl group of carnitine by carnitine palmitoyltransferase I, located on the cytosolic faces of the outer and inner mitochondrial membranes.
Acyl-carnitine is shuttled inside by a carnitine-acylcarnitine translocase, as a carnitine is shuttled outside.
Acyl-carnitine is converted back to acyl-CoA by carnitine palmitoyltransferase II, located on the interior face of the inner mitochondrial membrane. The liberated carnitine is shuttled back to the cytosol, as an acyl-CoA is shuttled into the matrix.

tag: ol

text: Beta oxidation, in the mitochondrial matrix, then cuts the long carbon chains of the fatty acids (in the form of acyl-CoA molecules) into a series of two-carbon (acetate) units, which, combined with co-enzyme A, form molecules of acetyl CoA, which condense with oxaloacetate to form citrate at the "beginning" of the citric acid cycle.[2] It is convenient to think of this reaction as marking the "starting point" of the cycle, as this is when fuel - acetyl-CoA - is added to the cycle, which will be dissipated as CO2 and H2O with the release of a substantial quantity of energy captured in the form of ATP, during the course of each turn of the cycle.

text:
Dehydrogenation by acyl-CoA dehydrogenase, yielding 1 FADH2
Hydration by enoyl-CoA hydratase
Dehydrogenation by 3-hydroxyacyl-CoA dehydrogenase, yielding 1 NADH + H+
Cleavage by thiolase, yielding 1 acetyl-CoA and a fatty acid that has now been shortened by 2 carbons (forming a new, shortened acyl-CoA)

text: The acetyl-CoA produced by beta oxidation enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate. This results in the complete combustion of the acetyl-CoA to CO2 and water. The energy released in this process is captured in the form of 1 GTP and 11 ATP molecules per acetyl-CoA molecule oxidized.[2][10] This is the fate of acetyl-CoA wherever beta oxidation of fatty acids occurs, except under certain circumstances in the liver.

text: In the liver oxaloacetate can be wholly or partially diverted into the gluconeogenic pathway during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled type 1 diabetes mellitus. Under these circumstances oxaloacetate is hydrogenated to malate which is then removed from the mitochondrion to be converted into glucose in the cytoplasm of the liver cells, from where it is released into the blood.[10] In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) insulin and high glucagon concentrations in the blood. Under these circumstances acetyl-CoA is diverted to the formation of acetoacetate and beta-hydroxybutyrate.[10] Acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone, are frequently, but confusingly, known as ketone bodies (as they are not "bodies" at all, but water-soluble chemical substances). The ketone bodies are released by the liver into the blood. All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver. Unlike free fatty acids, ketone bodies can cross the blood-brain barrier and are therefore available as fuel for the cells of the central nervous system, acting as a substitute for glucose, on which these cells normally survive.[10] The occurrence of high levels of ketone bodies in the blood during starvation, a low carbohydrate diet, prolonged heavy exercise and uncontrolled type 1 diabetes mellitus is known as ketosis, and, in its extreme form, in out-of-control type 1 diabetes mellitus, as ketoacidosis.

text: Fatty acids as an energy source[edit]

text: Fatty acids, stored as triglycerides in an organism, are an important source of energy because they are both reduced and anhydrous. The energy yield from a gram of fatty acids is approximately 9 kcal (37 kJ), compared to 4 kcal (17 kJ) for carbohydrates. Since the hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively anhydrous (water-free) environment. Carbohydrates, on the other hand, are more highly hydrated. For example, 1 g of glycogen can bind approximately 2 g of water, which translates to 1.33 kcal/g (4 kcal/3 g). This means that fatty acids can hold more than six times the amount of energy per unit of storage mass. Put another way, if the human body relied on carbohydrates to store energy, then a person would need to carry 31 kg (67.5 lb) of hydrated glycogen to have the energy equivalent to 4.6 kg (10 lb) of fat.[10]

text: Hibernating animals provide a good example for utilizing fat reserves as fuel. For example, bears hibernate for about 7 months, and, during this entire period, the energy is derived from degradation of fat stores. Migrating birds similarly build up large fat reserves before embarking on their intercontinental journeys.[15]

text: Thus the young adult human’s fat stores average between about 10–20 kg, but varies greatly depending on age, gender, and individual disposition.[16] By contrast the human body stores only about 400 g of glycogen, of which 300 g is locked inside the skeletal muscles and is unavailable to the body as a whole. The 100 g or so of glycogen stored in the liver is depleted within one day of starvation.[10] Thereafter the glucose that is released into the blood by the liver for general use by the body tissues, has to be synthesized from the glucogenic amino acids and a few other gluconeogenic substrates, which do not include fatty acids.[1] Please note however that lipolysis releases glycerol which can enter the pathway of gluconeogenesis.

text: Animals and plants synthesize carbohydrates from both glycerol and fatty acids[edit]

text: Fatty acids are broken down to acetyl-CoA by means of beta oxidation inside the mitochondria, whereas fatty acids are synthesized from acetyl-CoA outside the mitochondria, in the cytosol. The two pathways are distinct, not only in where they occur, but also in the reactions that occur, and the substrates that are used. The two pathways are mutually inhibitory, preventing the acetyl-CoA produced by beta-oxidation from entering the synthetic pathway via the acetyl-CoA carboxylase reaction.[1] It can also not be converted to pyruvate as the pyruvate dehydrogenase complex reaction is irreversible.[10] Instead the acetyl-CoA produced by the beta-oxidation of fatty acids condenses with oxaloacetate, to enter the citric acid cycle. During each turn of the cycle, two carbon atoms leave the cycle as CO2 in the decarboxylation reactions catalyzed by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. Thus each turn of the citric acid cycle oxidizes an acetyl-CoA unit while regenerating the oxaloacetate molecule with which the acetyl-CoA had originally combined to form citric acid. The decarboxylation reactions occur before malate is formed in the cycle.[1] Only plants possess the enzymes to convert acetyl-CoA into oxaloacetate from which malate can be formed to ultimately be converted to glucose.[1]

text: However acetyl-CoA can be converted to acetoacetate, which can decarboxylate to acetone (either spontaneously, or by acetoacetate decarboxylase). It can then be further metabolized to isopropanol which is excreted in breath/urine, or by CYP2E1 into hydroxyacetone (acetol). Acetol can be converted to propylene glycol. This converts to formate and acetate (the latter converting to glucose), or pyruvate (by two alternative enzymes), or propionaldehyde, or to L-lactaldehyde then L-lactate (the common lactate isomer).[17][18][19] Another pathway turns acetol to methylglyoxal, then to pyruvate, or to D-lactaldehyde (via S-D-lactoyl-glutathione or otherwise) then D-lactate.[18][20][21] D-lactate metabolism (to glucose) is slow or impaired in humans, so most of the D-lactate is excreted in the urine; thus D-lactate derived from acetone can contribute significantly to the metabolic acidosis associated with ketosis or isopropanol intoxication.[18] L-Lactate can complete the net conversion of fatty acids into glucose. The first experiment to show conversion of acetone to glucose was carried out in 1951. This, and further experiments used carbon isotopic labelling.[19] Up to 11% of the glucose can be derived from acetone during starvation in humans.[19]

text: The glycerol released into the blood during the lipolysis of triglycerides in adipose tissue can only be taken up by the liver. Here it is converted into glycerol 3-phosphate by the action of glycerol kinase which hydrolyzes one molecule of ATP per glycerol molecule which is phosphorylated. Glycerol 3-phosphate is then oxidized to dihydroxyacetone phosphate, which is, in turn, converted into glyceraldehyde 3-phosphate by the enzyme triose phosphate isomerase. From here the three carbon atoms of the original glycerol can be oxidized via glycolysis, or converted to glucose via gluconeogenesis.[10]

text: Other functions and uses of fatty acids[edit]

text: Intracellular signaling[edit]

text: Fatty acids are an integral part of the phospholipids that make up the bulk of the plasma membranes, or cell membranes, of cells. These phospholipids can be cleaved into diacylglycerol (DAG) and inositol trisphosphate (IP3) through hydrolysis of the phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), by the cell membrane bound enzyme phospholipase C (PLC).[22]

text: An example of a diacyl-glycerol shown on the right. This DAG is 1-palmitoyl-2-oleoyl-glycerol, which contains side-chains derived from palmitic acid and oleic acid. Diacylglycerols can also have many other combinations of fatty acids attached at either the C-1 and C-2 positions or the C-1 and C-3 positions of the glycerol molecule. 1,2 disubstituted glycerols are always chiral, 1,3 disubstituted glycerols are chiral if the substituents are different from each other.

text: Inositol trisphosphate (IP3) functions as an intracellular second messenger, which initiates the intracellular release of calcium ions (which activates intracellular enzymes, causes the release of hormones and neurotransmitters from the cells in which they are stored, and causes smooth muscle contraction when released by IP3), and the activation of protein kinase C (PKC), which is then translocated from the cell cytoplasm to the cell membrane. Although inositol trisphosphate, (IP3), diffuses into the cytosol, diacylglycerol (DAG) remains within the plasma membrane, due to its hydrophobic properties. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, whereas DAG is a physiological activator of protein kinase C (PKC), promoting its translocation from the cytosol to the plasma membrane. PKC is a multifunctional protein kinase which phosphorylates serine and threonine residues in many target proteins. However PKC is only active in the presence of calcium ions, and it is DAG that increases the affinity of PKC for Ca2+ and thereby renders it active at the physiological intracellular levels of this ion.[22]

text: Diacylglycerol and IP3 act transiently because both are rapidly metabolized. This is important as their message function should not linger after the message has been” received” by their target molecules. DAG can be phosphorylated to phosphatidate or it can be it can be hydrolysed to glycerol and its constituent fatty acids. IP3 is rapidly converted to into derivatives that that do not open calcium ion channels.[22]

text: Eicosanoid paracrine hormones[edit]

text: The prostaglandins are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are enzymatically derived from arachidonic acid a 20-carbon polyunsaturated fatty acid. Every prostaglandin therefore contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and form the prostanoid class of fatty acid derivatives.[23]

text: The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the membrane. This is catalyzed either by phospholipase A2 acting directly on a membrane phospholipid, or by a lipase acting on DAG (diacyl-glycerol). The arachidonate is then acted upon by the cyclooxygenase component of prostaglandin synthase. This forms a cyclopentane ring in roughly the middle of the fatty acid chain. The reaction also adds 4 oxygen atoms derived from two molecules of O2. The resulting molecule is prostaglandin G2 which is converted by the hydroperoxidase component of the enzyme complex into prostaglandin H2. This highly unstable compound is rapidly transformed into other prostaglandins, prostacyclin and thromboxanes.[23] These are then released into the interstitial fluids surrounding the cells that have manufactured the eicosanoid hormone.

text: If arachidonate is acted upon by a lipoxygenase instead of cyclooxygenase, Hydroxyeicosatetraenoic acids and leukotrienes are formed. They also act as local hormones.

text: Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. The discovery of the prostaglandin transporter (PGT, SLCO2A1), which mediates the cellular uptake of prostaglandin, demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. The release of prostaglandin has now also been shown to be mediated by a specific transporter, namely the multidrug resistance protein 4 (MRP4, ABCC4), a member of the ATP-binding cassette transporter superfamily. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear.

text: The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds. They act as autocrine or paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. Prostaglandins differ from endocrine hormones in that they are not produced at a specific site but in many places throughout the human body.

text: Prostaglandins have two derivatives: prostacyclins and thromboxanes. Prostacyclins are powerful locally acting vasodilators and inhibit the aggregation of blood platelets. Through their role in vasodilation, prostacyclins are also involved in inflammation. They are synthesized in the walls of blood vessels and serve the physiological function of preventing needless clot formation, as well as regulating the contraction of smooth muscle tissue.[24] Conversely, thromboxanes (produced by platelet cells) are vasoconstrictors and facilitate platelet aggregation. Their name comes from their role in clot formation (thrombosis).

text: Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage[edit]

text: A significant proportion of the fatty acids in the body are obtained from the diet, in the form of triglycerides of either animal or plant origin. The fatty acids in the fats obtained from land animals tend to be saturated, whereas the fatty acids in the triglycerides of fish and plants are often polyunsaturated and therefore present as oils.

text: These triglycerides, cannot be absorbed by the intestine.[25] They are broken down into mono- and di-glycerides plus free fatty acids (but no free glycerol) by pancreatic lipase, which forms a 1:1 complex with a protein called colipase (also a constituent of pancreatic juice), which is necessary for its activity. The activated complex can work only at a water-fat interface. Therefore, it is essential that fats are first emulsified by bile salts for optimal activity of these enzymes.[26] The digestion products consisting of a mixture of tri-, di- and monoglycerides and free fatty acids, which, together with the other fat soluble contents of the diet (e.g. the fat soluble vitamins and cholesterol) and bile salts form mixed micelles, in the watery duodenal contents (see diagrams on the right).[25][27]

text: The contents of these micelles (but not the bile salts) enter the enterocytes (epithelial cells lining the small intestine) where they are resynthesized into triglycerides, and packaged into chylomicrons which are released into the lacteals (the capillaries of the lymph system of the intestines).[28] These lacteals drain into the thoracic duct which empties into the venous blood at the junction of the left jugular and left subclavian veins on the lower left hand side of the neck. This means that the fat soluble products of digestion are discharged directly into the general circulation, without first passing through the liver, as all other digestion products do. The reason for this peculiarity is unknown.[29]

text: The chylomicrons circulate throughout the body, giving the blood plasma a milky, or creamy appearance after a fatty meal.[citation needed] Lipoprotein lipase on the endothelial surfaces of the capillaries, especially in adipose tissue, but to a lesser extent also in other tissues, partially digests the chylomicrons into free fatty acids, glycerol and chylomicron remnants. The fatty acids are absorbed by the adipocytes[citation needed], but the glycerol and chylomicron remnants remain in the blood plasma, ultimately to be removed from the circulation by the liver. The free fatty acids released by the digestion of the chylomicrons are absorbed by the adipocytes[citation needed], where they are resynthesized into triglycerides using glycerol derived from glucose in the glycolytic pathway[citation needed]. These triglycerides are stored, until needed for the fuel requirements of other tissues, in the fat droplet of the adipocyte.

text: The liver absorbs a proportion of the glucose from the blood in the portal vein coming from the intestines. After the liver has replenished its glycogen stores (which amount to only about 100 g of glycogen when full) much of the rest of the glucose is converted into fatty acids as described below. These fatty acids are combined with glycerol to form triglycerides which are packaged into droplets very similar to chylomicrons, but known as very low-density lipoproteins (VLDL). These VLDL droplets are handled in exactly the same manner as chylomicrons, except that the VLDL remnant is known as an intermediate-density lipoprotein (IDL), which is capable of scavenging cholesterol from the blood. This converts IDL into low-density lipoprotein (LDL), which is taken up by cells that require cholesterol for incorporation into their cell membranes or for synthetic purposes (e.g. the formation of the steroid hormones). The remainder of the LDLs is removed by the liver.[30]

text: Adipose tissue and lactating mammary glands also take up glucose from the blood for conversion into triglycerides. This occurs in the same way as it does in the liver, except that these tissues do not release the triglycerides thus produced as VLDL into the blood. Adipose tissue cells store the triglycerides in their fat droplets, ultimately to release them again as free fatty acids and glycerol into the blood (as described above), when the plasma concentration of insulin is low, and that of glucagon and/or epinephrine is high.[31] Mammary glands discharge the fat (as cream fat droplets) into the milk that they produce under the influence of the anterior pituitary hormone prolactin.

text: All cells in the body need to manufacture and maintain their membranes and the membranes of their organelles. Whether they rely for this entirely on free fatty acids absorbed from the blood, or are able to synthesize their own fatty acids from the blood glucose, is not known. The cells of the central nervous system will almost certainly have the capability of manufacturing their own fatty acids, as these molecules cannot reach them through the blood brain barrier, while, on the other hand, no cell in the body can manufacture the required essential fatty acids which have to be obtained from the diet and delivered to each cell via the blood.

text: Fatty acid synthesis[edit]

text: Much like beta-oxidation, straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon palmitic acid is produced.[32][33]

text: The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli.[32] These reactions are performed by fatty acid synthase II (FASII), which in general contain multiple enzymes that act as one complex. FASII is present in prokaryotes, plants, fungi, and parasites, as well as in mitochondria.[34]

text: In animals, as well as some fungi such as yeast, these same reactions occur on fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. FASI is less efficient than FASII; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination.[34]

text: Once a 16:0 carbon fatty acid has been formed, it can undergo a number of modifications, resulting in desaturation and/or elongation. Elongation, starting with stearate (18:0), is performed mainly in the ER by several membrane-bound enzymes. The enzymatic steps involved in the elongation process are principally the same as those carried out by FAS, but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated.[35][36]

text:
Step
Enzyme
Reaction
Description

(a)
Acetyl CoA:ACP transacylase

Activates acetyl CoA for reaction with malonyl-ACP

(b)
Malonyl CoA:ACP transacylase

Activates malonyl CoA for reaction with acetyl-ACP

(c)
3-ketoacyl-ACP synthase

Reacts priming acetyl-ACP with chain-extending malonyl-ACP.

(d)
3-ketoacyl-ACP reductase

Reduces the carbon 3 ketone to a hydroxyl group

(e)
3-Hydroxyacyl ACP dehydrase

Removes water

(f)
Enoyl-ACP reductase

Reduces the C2-C3 double bond.

text: Abbreviations: ACP – Acyl carrier protein, CoA – Coenzyme A, NADP – Nicotinamide adenine dinucleotide phosphate.

text: Note that during fatty synthesis the reducing agent is NADPH, whereas NAD is the oxidizing agent in beta-oxidation (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions.[37] (Thus NADPH is also required for the synthesis of cholesterol from acetyl-CoA; while NADH is generated during glycolysis.) The source of the NADPH is two-fold. When malate is oxidatively decarboxylated by “NADP+-linked malic enzyme" pyruvate, CO2 and NADPH are formed. NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids, or it can be catabolized to pyruvate.[37]

text: Glycolytic end products are used in the conversion of carbohydrates into fatty acids[edit]

text: In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation. The cells of the central nervous system probably also make most of the fatty acids needed for the phospholipids of their extensive membranes from glucose, as blood-born fatty acids cannot cross the blood brain barrier to reach these cells.[37] However, how the essential fatty acids, which mammals cannot synthesize themselves, but are nevertheless important components of cell membranes (and other functions described above) reach them is unknown.

text: The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol.[37] This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol.[37] There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion).[38] The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids.[38][39]

text: Regulation of fatty acid synthesis[edit]

text: Acetyl-CoA is formed into malonyl-CoA by acetyl-CoA carboxylase, at which point malonyl-CoA is destined to feed into the fatty acid synthesis pathway. Acetyl-CoA carboxylase is the point of regulation in saturated straight-chain fatty acid synthesis, and is subject to both phosphorylation and allosteric regulation. Regulation by phosphorylation occurs mostly in mammals, while allosteric regulation occurs in most organisms. Allosteric control occurs as feedback inhibition by palmitoyl-CoA and activation by citrate. When there are high levels of palmitoyl-CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl-CoA carboxylase to prevent a build-up of fatty acids in cells. Citrate acts to activate acetyl-CoA carboxylase under high levels, because high levels indicate that there is enough acetyl-CoA to feed into the Krebs cycle and produce energy.[40]

text: High plasma levels of insulin in the blood plasma (e.g. after meals) cause the dephosphorylation of acetyl-CoA carboxylase, thus promoting the formation of malonyl-CoA from acetyl-CoA, and consequently the conversion of carbohydrates into fatty acids, while epinephrine and glucagon (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting lipogenesis in favor of fatty acid oxidation via beta-oxidation.[37][39]

text: Disorders[edit]

text: Disorders of fatty acid metabolism can be described in terms of, for example, hypertriglyceridemia (too high level of triglycerides), or other types of hyperlipidemia. These may be familial or acquired.

text: Familial types of disorders of fatty acid metabolism are generally classified as inborn errors of lipid metabolism. These disorders may be described as fatty oxidation disorders or as a lipid storage disorders, and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types.


document_title: NCIS (TV series)

question_text: when did the new season of ncis la start

root

text: NCIS (TV series)

text: Premise[edit]

text: NCIS follows a fictional team of Naval Criminal Investigative Service Major Case Response Team (MCRT)[10] special agents based at the Washington, D.C. field office in Washington Navy Yard.[11] In real life, the field office is based at the nearby Joint Base Anacostia-Bolling[12] while the Navy Yard is home to the museum and several military commands within the Department of the Navy. It is described by the actors and producers (on special features on DVD releases in the United States) as being distinguished by its comedic elements, ensemble acting, and character-driven plots. The NCIS is the primary law enforcement and counterintelligence arm of the United States Department of the Navy, which includes the United States Marine Corps. NCIS investigates all major criminal offenses (felonies) – for example, crimes punishable under the Uniform Code of Military Justice by confinement of more than one year – within the Department of the Navy.

tag: p

text: Plot[edit]

text: Whenever a crime is committed involving Navy or Marine personnel, the Washington-based Major Case Response Team—an elite arm of the Naval Criminal Investigative Service—spearheads the investigation. The team, led by laconic investigator Leroy Jethro Gibbs (Mark Harmon), has included Caitlin Todd (Sasha Alexander), Anthony DiNozzo (Michael Weatherly), Timothy McGee (Sean Murray), Ziva David (Cote de Pablo), Eleanor Bishop (Emily Wickersham), Alexandra Quinn (Jennifer Esposito), and Nicholas Torres (Wilmer Valderrama). Over the course of the series, they are further assisted by allies both foreign and domestic, including Dr. Donald Mallard (David McCallum), Dr. Jimmy Palmer (Brian Dietzen), forensic specialist Abby Sciuto (Pauley Perrette), British intelligence officer Clayton Reeves (Duane Henry), and successive NCIS Directors Jennifer Shepard (Lauren Holly) and Leon Vance (Rocky Carroll).

text: Cast and characters[edit]

text:
Mark Harmon as Leroy Jethro Gibbs, NCIS Supervisory Special Agent
Sasha Alexander as Caitlin "Kate" Todd, Secret Service Agent, NCIS Special Agent (seasons 1–2; guest seasons 3, 8, 9, and 12)
Michael Weatherly as Anthony "Tony" DiNozzo, NCIS Senior Special Agent (seasons 1–13)
Pauley Perrette as Abby Sciuto, NCIS Forensic Specialist (seasons 1–15)[13]
David McCallum as Dr. Donald "Ducky" Mallard, NCIS Chief Medical Examiner
Sean Murray as Timothy "Tim" McGee, NCIS Special Agent (recurring season 1; main season 2–present)
Cote de Pablo as Ziva David, Mossad Officer, NCIS Special Agent (seasons 3–11)
Lauren Holly as Jenny Shepard, NCIS Director (seasons 3–5; guest seasons 9, and 12)
Rocky Carroll as Leon Vance, NCIS Director (recurring season 5; main seasons 6–present)
Brian Dietzen as Dr. Jimmy Palmer, NCIS Assistant Medical Examiner (recurring seasons 1–9; main seasons 10–present)
Emily Wickersham as Eleanor Bishop, NSA Analyst, NCIS Special Agent (seasons 11–present)
Wilmer Valderrama as Nicholas Torres, NCIS Special Agent (seasons 14–present)
Jennifer Esposito as Alexandra Quinn, NCIS Special Agent (season 14)
Duane Henry as Clayton Reeves, British Secret Intelligence Service (MI6) Officer (guest season 13; main season 14–present)
Maria Bello as Dr Jacqueline "Jack" Sloane, NCIS Special Agent, operational psychologist (season 15)

tag: ul

text: Production[edit]

text: Name[edit]

text: Prior to the launch of the first season, advertisements on CBS identified the show as "Naval CIS". By the time of the launch of the first episode, NCIS was airing under the name Navy NCIS, the name it held for the entire first season. Since the "N" in NCIS stands for "Naval", the name "Navy NCIS" was redundant. The decision to use this name was reportedly made by CBS, over the objections of Bellisario,[14] to:

text:
Attract new viewers (particularly those of JAG), who might not know the NCIS abbreviation
Distinguish between NCIS and the similarly themed and similarly spelled CBS series CSI and its spinoffs. (The original title, for instance, was often misquoted and parodied as "Navy CSI", something the show itself referenced in the first episode.)[15]

text: Flair[edit]

text: From the season-two episode "Lt. Jane Doe" onwards, the series began showing two-second-long black-and-white clips. These clips are shown at the beginning of every segment depicting the last two seconds of that segment, a segment being the five or six portions of the show meant to be separated by commercials. In the season-three premiere, "Kill Ari (Part I)", a freeze-frame shot was also used with the very end of most episodes turned into a freeze frame, as well.

text: Crew changes[edit]

text: It was reported in May 2007 that Donald Bellisario would be stepping down from the show.[16] Due to a disagreement with series star Mark Harmon, Bellisario's duties as showrunner/head writer were to be given to long-time show collaborators, including co-executive producer Chas. Floyd Johnson and Shane Brennan, with Bellisario retaining his title as executive producer.[17] In fall 2009,[clarification needed] Gary Glasberg joined the crew and became the new "day-to-day" runner of NCIS, as Shane Brennan had to focus on his new show, the spin-off NCIS: Los Angeles.[18] On September 28, 2016, Glasberg died in his sleep at the age of 50.[19]

text: On April 5, 2016, long-time director Dennis Smith announced he had completed his final episode as part of the NCIS crew, though to which episode he was referring was not specified.[20]

text: Episodes[edit]

text: On February 29, 2016, the series was renewed for a fourteenth and fifteenth season.[21][22] As of November 7, 2017,[update] 337 episodes of NCIS have aired.[2]

text:
Season
Episodes
Originally aired

First aired
Last aired

Intro
2
April 22, 2003 (2003-04-22)
April 29, 2003 (2003-04-29)

1
23
September 23, 2003 (2003-09-23)
May 25, 2004 (2004-05-25)

2
23
September 28, 2004 (2004-09-28)
May 24, 2005 (2005-05-24)

3
24
September 20, 2005 (2005-09-20)
May 16, 2006 (2006-05-16)

4
24
September 19, 2006 (2006-09-19)
May 22, 2007 (2007-05-22)

5
19
September 25, 2007 (2007-09-25)
May 20, 2008 (2008-05-20)

6
25
September 23, 2008 (2008-09-23)
May 19, 2009 (2009-05-19)

7
24
September 22, 2009 (2009-09-22)
May 25, 2010 (2010-05-25)

8
24
September 21, 2010 (2010-09-21)
May 17, 2011 (2011-05-17)

9
24
September 20, 2011 (2011-09-20)
May 15, 2012 (2012-05-15)

10
24
September 25, 2012 (2012-09-25)
May 14, 2013 (2013-05-14)

11
24
September 24, 2013 (2013-09-24)
May 13, 2014 (2014-05-13)

12
24
September 23, 2014 (2014-09-23)
May 12, 2015 (2015-05-12)

13
24
September 22, 2015 (2015-09-22)
May 17, 2016 (2016-05-17)

14
24
September 20, 2016 (2016-09-20)
May 16, 2017 (2017-05-16)

15
22[23]
September 26, 2017 (2017-09-26)
TBA

tag: table

text: Backdoor pilots[edit]

text: JAG[edit]

text: Two episodes of JAG season 8, "Ice Queen" and "Meltdown", serve as the back-door pilot of NCIS itself.

text: These JAG episodes introduced Mark Harmon as Gibbs, Michael Weatherly as Tony, Robyn Lively as Vivian Blackadder, Pauley Perrette as Abby, and David McCallum as Ducky.

text: Patrick Labyorteaux appears on NCIS reprising his JAG role as Lt. Bud Roberts in the first-season episode "Hung Out to Dry", and in the fourteenth-season episode "Rogue"; Alicia Coppola returned as Lt. Cmdr. Faith Coleman in "UnSEALed", "Call of Silence", and "Hometown Hero", while Adam Baldwin returned as Cmdr. Michael Rainer in "A Weak Link", and John M. Jackson appeared as retired Rear Admiral A. J. Chegwidden in the season-10 episode "Damned If You Do".

text: NCIS: Los Angeles[edit]

text: The two-part NCIS episode "Legend" serves as the back-door pilot of NCIS: Los Angeles.

text: "Legend" introduces Chris O'Donnell as G. Callen, LL Cool J as Sam Hanna, Daniela Ruah as Kensi Blye, and Barrett Foa as Eric Beale.

text: Rocky Carroll recurs on NCIS: Los Angeles as his NCIS character Director Leon Vance, while Pauley Perrette has appeared twice as Abby, and Michael Weatherly has appeared once as Anthony DiNozzo. NCIS guest stars reprising roles between series include David Dayan Fisher as CIA Officer Trent Kort, in the season-one finale of NCIS: Los Angeles; Kelly Hu as Lee Wuan Kai in NCIS: Los Angeles and later in an episode of NCIS.

text: John M. Jackson has appeared on NCIS: Los Angeles' as his JAG character Admiral A. J. Chegwidden, while this series has also crossed over with Hawaii Five-0 and Scorpion.

text: NCIS: New Orleans[edit]

text: The two-part NCIS episode "Crescent City" serves as the back-door pilot of NCIS: New Orleans.

text: "Crescent City" introduces Scott Bakula as Dwayne Pride, Lucas Black as Christopher LaSalle, Zoe McLellan as Meredith Brody, and CCH Pounder as Loretta Wade.

text: Rocky Carroll recurs as Director Leon Vance, while NCIS series regulars Mark Harmon, Michael Weatherly, Pauley Perrette, Sean Murray, Emily Wickersham, Wilmer Valderrama, David McCallum and Brian Dietzen have all appeared as their NCIS characters. NCIS recurring cast members Meredith Eaton, Joe Spano, Diane Neal, and Leslie Hope have all guest-starred on NCIS: New Orleans.

text: Release[edit]

text: Broadcast[edit]

text: NCIS airs on Network Ten and TV Hits (formerly TV1)[24] in Australia,[25][26][27][28][29][30][31] Global (syndicated on Showcase and Lifetime) in Canada, TV3 and The Box in New Zealand, Seriale+ (premieres), TVN (free-TV premieres), TVN7 (reruns), AXN (reruns) and TV Puls (reruns) in Poland, and Fox, CBS Action, Universal Channel, Channel 5 and 5USA in the United Kingdom.

text: Home video releases[edit]

text: The first 11 seasons of NCIS have been released in Regions 1, 2, and 4. In Germany (Region 2), seasons 1–4 and 6–8 were released in two separate sets for each season. The first-season DVD omits the two introductory episodes from season eight of JAG, though they are featured on the JAG season-eight DVD.

text: Other releases[edit]

text: In 2010, CBS Interactive and GameHouse released a mobile video game, NCIS: The Game for iOS, Android, BlackBerry, Windows Mobile, and BREW/J2ME. The game features five different cases written by the show's writers.[32]

text: On November 1, 2011, Ubisoft released a video game adaption of NCIS for the PC, Xbox 360, PlayStation 3, and Wii. A Nintendo 3DS version was released on March 6, 2012. The video game was deemed as a mockery of the show by reviewers and players alike, and received a 2/10 rating on GameSpot.[33]

text: There's also a Facebook and mobile game called NCIS: Hidden Crimes.[34][35]

text: TV movies[edit]

text: In the UK, certain NCIS multi-part episodes were edited together to make a combined feature and shown on Channel 5, 5USA, CBS Action and Fox UK. These include:

text:
Title
Episodes edited together
Air date
Runtime
Source

The NCIS Movie: Enemies
"Enemies Foreign" / "Enemies Domestic"
May 20, 2013
1 hr, 20 mins
[36][37]

The NCIS Movie: Judgement Day
"Judgment Day (Part I)" / "Judgment Day (Part II)"
June 10, 2013
1 hr, 40 mins
[38]

The NCIS Movie: Legend
(Legend Compilation)
"Legend (Part I)" / "Legend (Part II)"
June 10, 2013
1 hr, 45 mins
[39][40]

The NCIS Movie: Kill Ari
"Kill Ari (Part I)" / "Kill Ari (Part II)"
August 22, 2013
2 hrs
[41][42]

The NCIS Movie: War on Terror
"Engaged (Part I)" / "Engaged (Part II)"
February 1, 2014
1 hr, 20 mins
[43]

The NCIS Movie: Payback
"Borderland" / "Patriot Down" / "Rule Fifty-One"
March 1, 2014
2 hrs, 35 mins
[44]

The NCIS Movie: Shell Shock
"Shell Shock (Part I)" / "Shell Shock (Part II)"
April 11, 2014
1 hr, 30 mins
[45]

Death Wish (Part I & II)
"Shabbat Shalom" / "Shiva"
April 16, 2014 (1)
April 18, 2014 (2)
1 hr, 40 mins
[46][47]

The NCIS Movie:
Race Against Terror: Hiatus
"Hiatus (Part I)" / "Hiatus (Part II)"

August 20, 2016
September 17, 2016

1 hr, 50 mins
[48][49]

text: Soundtrack[edit]

text: CBS Records released the show's first soundtrack on February 10, 2009.[50] The Official TV Soundtrack is a two-disc, 22-track set that includes brand new songs from top artists featured prominently in upcoming episodes of the series, as well as the show's original theme by Numeriklab[51] (available commercially for the first time) and a remix of the theme by Ministry. The set also includes songs performed by series regulars Pauley Perrette and Coté de Pablo.

text: A sequel to the soundtrack was released on November 3, 2009. NCIS: The Official TV Soundtrack; Vol. 2 is a single-disc, 12-track set that covers songs (many previously unreleased) featured throughout the seventh season of the show, including one recording titled "Bitter and Blue" by Weatherly, as well as two songs used in previous seasons.

text: Reception[edit]

text: In 2016, The New York Times reported that NCIS "is most popular in rural areas", especially in rural Maine and Pennsylvania.[52]

text: Broadcast ratings[edit]

text: Seasonal rankings (based on average total viewers per episode) of NCIS.

text:
Broadcast ratings

Season
Episodes
Timeslot (EST)
Original airing
Live television ratings

Season premiere
Season finale
TV season
Viewers
(in millions)
Rank
(viewers)
Key demographics
(18–49)

1st
23
Tuesday 8:00 PM
September 23, 2003
May 25, 2004
2003–04
11.84[53]
26th
N/A

2nd
23
September 28, 2004
May 24, 2005
2004–05
13.57[54]
22nd
N/A

3rd
24
September 20, 2005
May 16, 2006
2005–06
15.27[55]
16th
N/A

4th
24
September 19, 2006
May 22, 2007
2006–07
14.54[56]
20th
N/A

5th
19
September 25, 2007
May 20, 2008
2007–08
14.41[57]
14th
N/A

6th
25
September 23, 2008
May 19, 2009
2008–09
17.77[58]
5th
N/A

7th
24
September 22, 2009
May 25, 2010
2009–10
19.33[59]
4th
4.1[59]

8th
24
September 21, 2010
May 17, 2011
2010–11
19.46[60]
5th
4.1[61]

9th
24
September 20, 2011
May 15, 2012
2011–12
19.49[62]
3rd
4.01[63]

10th
24
September 25, 2012
May 14, 2013
2012–13
21.34[4]
1st
4.0[4]

11th
24
September 24, 2013
May 13, 2014
2013–14
19.77[64]
3rd
3.3[65]

12th
24
September 23, 2014
May 12, 2015
2014–15
18.25[66]
3rd
2.43[67]

13th
24
September 22, 2015
May 17, 2016
2015–16
16.61[68]
3rd
2.2[69]

14th
24
September 20, 2016
May 16, 2017
2016–17
14.63[70]
3rd

15th
22
September 26, 2017

2017–18

text:
Ever since season 7, NCIS has been the most watched scripted show on American television, but it was only in the 2012–13 season that it ranked number 1 as the most watched program of the past year, surpassing both American Idol and NBC Sunday Night Football that had ranked above it the past three seasons.
On January 15, 2013, NCIS surpassed its previous series high in viewers, with the season ten episode "Shiva" attracting 22.86 million viewers.[71]

text: DVR[edit]

text:
The show ranked number four in DVR playback (2.714 million viewers), according to Nielsen prime DVR lift data from January 5–11, 2009.[72]
The show ranked number thirteen in DVR playback (2.743 million viewers), according to Nielsen prime DVR lift data from February 9–15, 2009.[73]
The show ranked number nine in DVR playback (3.007 million viewers), according to Nielsen prime DVR lift data from April 6–12, 2009.[74]

text: Cable[edit]

text:
The show ranked number eighteen (4.793 million viewers) in the list of Nielsen ratings top twenty most-watched cable shows for the week ending January 25, 2009.[75]
The show ranked number ten (4.535 million viewers), twelve (4.264 million viewers), thirteen (4.221 million viewers), fifteen (4,161 million viewers), seventeen (4.132 million viewers), and twenty (4.081 million viewers) in the list of Nielsen ratings top twenty most-watched cable shows for the week ending March 1, 2009.[76]
The show ranked sixteen (4.091 million viewers), seventeen (4.084 million viewers), eighteen (4.072 million viewers), and twenty (4.006 million viewers) in the list of Nielsen ratings top twenty most-watched cable shows for the week ending March 29, 2009.[77]
The show ranked number five (4.492 million viewers), six (4.467 million viewers), eight (4.394 million viewers), nine (4.214 million viewers), fifteen (3.962 million viewers), and seventeen (3.8.58 million viewers) in the list of Nielsen ratings top twenty most-watched cable shows for the week ending May 3, 2009.[78]
The show ranked number three (4.82 million viewers), six (4.38 million viewers), ten (3.82 million viewers), eleven (3.88 million viewers), and fourteen (3.87 million viewers) in the list of Nielsen ratings top fifteen most-watched cable shows for the week ending November 1, 2009.[79]

text: Franchise[edit]

text: NCIS has produced two spin-offs: NCIS: Los Angeles (2009–) and NCIS: New Orleans (2014–).

text: NCIS: Los Angeles[edit]

text: In 2009, CBS picked up an NCIS spin-off series with the title NCIS: Los Angeles,[80][81][82][83] with the backdoor pilot, "Legend", airing on April 28, 2009 and May 5, 2009.[81] The backdoor pilot introduced Chris O'Donnell as Special Agent G. Callen, LL Cool J as Special Agent Sam Hanna, Louise Lombard as Special Agent Lara Macy, Peter Cambor as Operational Psychologist Nate Getz: and Daniela Ruah as Special Agent Kensi Blye.[84] The crew for the series includes Michael B. Kaplan, Lev L. Spiro, Jerry London, Sheldon Epps, and Mark Saraceni.[85]

text: Following the show's official pick-up by CBS, it was confirmed that Louise Lombard had not been signed to continue her role as Special Agent Lara Macy. Linda Hunt and Adam Jamal Craig were confirmed to replace her in starring roles, playing OSP Manager Henrietta Lange and Special Agent Dom Vail respectively. Craig, who left the series in episode 21 of season 1, was replaced by Eric Christian Olsen playing Marty Deeks.[86]

text: Characters from NCIS have appeared in the spin-off. Rocky Carroll portrayed Leon Vance in a recurring role,[87][88] while Pauley Perrette portrayed Abby Sciuto and appeared in the season 1 episodes "Killshot"[87] and "Random on Purpose".[88]

text: NCIS: Los Angeles was created by Shane Brennan. In April 2011, NCIS creator Donald Bellisario sued CBS over NCIS: Los Angeles because of his contract which gave him "first opportunity" to develop a spin-off or sequel,[89] the lawsuit was dismissed by a judge in June 2012.[90] However, discussions continued between CBS and Bellisario and in January 2013 the dispute was settled outside of court a week before it was set to go to trial; the terms of the agreement were not disclosed but were described as being amicable.[91][92][93]

text: NCIS: New Orleans[edit]

text: In September 2013 CBS announced a planned second spin-off series set in New Orleans that would be introduced via a planted two-part backdoor pilot NCIS episode. The episodes were filmed in February 2014 and aired on March 25, 2014 and April 1, 2014. NCIS star Mark Harmon and showrunner Gary Glasberg are the executive producers, and CBS Studios produces the series.[94] "Crescent City", the two-part backdoor-pilot episode was initially "supposed to be just an idea for an episode". Glasberg discussed the idea of the episode with Harmon, who said "That's more than a[n] [...] episode".[95] The premise for the episodes are, according to Glasberg, "all about this tiny little NCIS office that's down [in New Orleans], and the kind of cases that they come across".[96]

text: The series stars Scott Bakula as Special Agent Dwayne Cassius Pride, Lucas Black as Special Agent Christopher LaSalle, Zoe McLellan as Special Agent Meredith "Merri" Brody, Rob Kerkovich as Sebastian Lund, and C. C. H. Pounder as Dr. Loretta Wade.[97][98][99] Daryl "Chill" Mitchell, Shalita Grant and Vanessa Ferlito joined the main cast later, portraying computer specialist Patton Plame, Special Agent Sonja Percy, and Special Agent Tammy Gregorio, respectively.

text: On May 9, 2014, NCIS: New Orleans was picked up by CBS[100] and was renewed for a second season on January 12, 2015.[101]

text: NCIS and NCIS: New Orleans have had two crossovers.

text:
"Sister City"—Abby's brother is suspected of poisoning the passengers and crew of a private plane flying from New Orleans to Washington, D.C.
"Pandora's Box"—A theoretical terror playbook is stolen and put up for auction on the black market when Abby's homeland security think tank is compromised.

text: Awards and nominations[edit]

text: NCIS has received many awards and nominations since it premiered on September 23, 2003 including the ALMA Awards, ASCAP Awards, BMI Film & TV Awards, Emmy Awards, and People's Choice Awards.


document_title: Law & Order: Special Victims Unit (season 19)

question_text: when does law and order svu come back on

text: Production[edit]

text: Law & Order: Special Victims Unit was renewed for a nineteenth season on May 12, 2017.[1] Michael S. Chernuchin, who had previously worked on Law & Order, Law & Order: Criminal Intent and Chicago Justice took over from Rick Eid as showrunner, after Eid left to be showrunner for the fifth season of Chicago P.D. after only one season as showrunner.[2] Production on the season started on July 20, 2017.[3] On January 9, 2018, NBC ordered an extra two episodes for season nineteen, as confirmed in a tweet by Robert Brooks Cohen.[4]

text: Storylines[edit]

text: Showrunner/executive producer Michael Chernuchin told The Hollywood Reporter that this season of SVU would be 'ripping the headlines' of more current and political events such as the Charlottesville riots. Chernuchin noting, "Conflict. It's just the state of the world today with everybody. Everybody's political now and everything is political now and we want to deal with that." Kate Stanhope at THR also mentioned to Chernuchin about the pulled episode ("Unstoppable") from last season, asking him if he was hesitant about diving into politics this season. Chernuchin replied, "I'm not going to choose a side. I won't choose a side. I'm going to present both political views and let the audience decide which one is right. My goal, and I told the writers on this on the first day of our writers' room, is at the end of every episode, I want half the audience to throw their shoes at the television and the other half to stand up and cheer."[5]

text: Another episode Chernuchin told THR would be based on the Charlie Gard case, an infant in England who was born with a rare genetic disorder that causes progressive brain damage and muscle failure. "That's a life and death story," Chernuchin explained. "Cat-fishing," cyberbullying — which he described to THR as "[SVU's] answer to 13 Reasons Why — and an airplane episode covering "all the turmoil on airplanes these days." Chernuchin concluded, "We are ripping things from the headlines. Some of them are big, famous headlines and some of them are smaller headlines."[5]

text: On September 8, 2017, Chernuchin gave an overview of the season premiere and outlook on the season as a whole to TV Line; noting that A.D.A. Barba (Raúl Esparza) would start having other problems than court battles when Peter Stone (Philip Winchester) shows up, Stone pushing Barba into "a huge moral decision." Chernuchin also teased that Lieutenant Benson's life would be getting worse before it gets any better, "What I told Mariska [Hargitay] when I came aboard is, 'You're a broken woman, because of your past, and I'm going to drag you through the woods and you're gonna come out the other side a better person," he previewed. "So we're gonna throw the kitchen sink at her [Benson]." He also mentioned there's a possibility of romance for Benson: "There might be, she's not looking for it, but it might happen."[6] In an interview with E! News, Kelli Giddish (Det. Amanda Rollins) says a change in Benson and Rollins' relationship dynamic is coming. "I'm so looking forward to developing a friendship with Benson, the Rollins and Benson relationship, because they have so much in common." Benson and Rollins' relationship being rocky, most notably between seasons fifteen and eighteen as Benson began 'moving up the ranks' to Sergeant and then Lieutenant. "They have been at odds, it's just nice to come into that office and know that we're not going to fight and kind of support each other as I think these two characters would in real life," Giddish continued.[7]

text: An episode based on the Harvey Weinstein sexual abuse allegations aired on January 17, 2018.[8] "We are hitting Harvey Weinstein head-on, but it's not in the realm of the entertainment business," Michael Chernuchin said in an interview with Entertainment Weekly. "It's a real important episode about the rape culture in an industry, and we wanted to try [to] stretch the law to criminalize that sort of environment."

text: Cast[edit]

text: The entire main cast from the previous season returned. In August 2017, it was announced that Philip Winchester would reprise his role as Assistant State's Attorney Peter Stone from Chicago Justice, appearing around the midpoint of the season.[9][10] New show runner/executive producer Michael Chernuchin told Entertainment Weekly that Stone's character would be coming in as an antagonist and that he will be a foil for A.D.A. Barba (Raúl Esparza) this season; Stone's character isn't necessarily taking his [Barba's] job. "There's more than one A.D.A. in New York [...] Philip will come in and he won't be the nicest person our characters have ever met. What he's going to be doing, too, is basically bringing all of the franchises into one. He's connecting Law & Order, the Chicago franchises and now SVU."[11] His character debuted in the thirteenth episode of the season.[12][13] In the thirteenth episode, Raúl Esparza departed the cast after six seasons on the show.[14] He told Natalie Abrams of Entertainment Weekly that it was his decision to leave, adding "I've done six seasons, I felt like it was time to go. I had explored a lot of what I thought Barba was about. I just felt it was time to move on."[14] Philip Winchester took his place as the show's permanent A.D.A, guest starring in Esparza's final episode before being promoted to main cast in the fourteenth episode.

text: Main cast[edit]

text:
Mariska Hargitay as Lieutenant Olivia Benson
Kelli Giddish as Detective Amanda Rollins
Ice-T as Detective Odafin "Fin" Tutuola
Peter Scanavino as Detective Dominick "Sonny" Carisi, Jr.
Raúl Esparza as A.D.A. Rafael Barba (episodes 1–13)
Philip Winchester as A.D.A. Peter Stone (episode 14 onwards; guest star: episode 13)

text: Special guest star[edit]

text: Sam Waterston as DA Jack McCoy

text: Recurring cast[edit]

text:
Dean Winters as DA Investigator Brian Cassidy
Ryan Buggle as Noah Porter-Benson
Barbara Miluski as Judge Lisa Peck
Peter Jacobson as Defence Attorney Randy Dworkin
Vincent Curatola as Judge Al Burtuccio
Brooke Shields as Sheila Porter
Ami Brabson as Judge Karyn Blake
Peter Hermann as Defence Attorney Trevor Langan
Steve Rosen as Defence Attorney Michael Guthrie
Helmar Augustus Cooper as Judge Reginald Flowers
Jayne Houdyshell as Judge Ruth Linden
Peter Gallagher as Deputy Chief William Dodds
Maureen Mueller as Counselor Susan Janet
Jenna Stern as Judge Elana Barth
Tamara Tunie as Medical Examiner Melinda Warner
Carolyn McCormick as Psychologist Elizabeth Olivet
Ned Eisenberg as Defence Attorney Roger Kressler
Sonia Manzano as Judge Gloria Pepitone
Joe Grifasi as Judge Hashi Horowitz

text: Guest stars[edit]

text: It was announced on August 11, 2017 by The Hollywood Reporter that actress Brooke Shields would play a 'major' recurring role throughout the course of the season. "I play a very different character from any I have ever played," Shields commented. "I'm excited to stir the SVU pot a bit." THR noted that details of her role are being kept under wraps, although it's been teased that Shields' role will "shake up Benson's (Mariska Hargitay) world."[10] At the New York Fashion Week event on September 7, 2017, Shields talked about her "complicated" character; "We're discovering the character," she said of her at the time, mysterious recurring role, "it's pretty complicated and it's gut wrenching. What's so amazing about the show is that the characters are so rich and layered, and they're just filtering me through it." Shields also noted that her character was set to begin appearing in the third episode ("Contrapasso") of the season.[15] In that episode's last scene, Shields' character was revealed to be Noah's previously unknown grandmother, Sheila Porter, who challenged Benson for custody before becoming friends. Her story arc finished in 2018 when Sheila abducted Noah in a cliffhanger episode, before being caught by Benson and the squad and arrested.

text: On August 18, Entertainment Weekly released a sneak-peak of the script of SVU's season 19 premiere episode and announced that Will Chase would be guest starring as Byron Marks, an accused rapist who turned fugitive when he fled to Cuba six years prior, he is caught by Fin (Ice T) in the premiere's opening scenes. Amy Smart guest starred as one of Marks' victims, and Peter Jacobson – who previously guest starred in the thirteenth-season finale and recurred in season fourteen as a pimp named Bart Ganzel – guest starred in the premiere as his recurring mothership Law & Order character, Defense Attorney Randy Dworkin, a character created by Michael Chernuchin during his tenure on L&O.[16] Annabeth Gish guest starred in the third episode of the season. She portrayed a defense attorney in a case where a man is castrated and left for dead; leading the SVU squad to three female suspects with possible motives.[17] Cleveland Cavaliers point guard Isaiah Thomas, made a cameo appearance as himself in an October episode ("Complicated") of SVU. Thomas' cameo appearance occurs in the midst of a missing persons investigation.[18]

text: Mike Faist, a Tony Award-nominated actor starring as Connor Murphy in Broadway musical Dear Evan Hansen, guest starred as a young man struggling with the long-ago disappearance of his sister in "Complicated".[19] The Walking Dead alum, Brighton Sharbino guest starred as a teenager who disappears when her classmates make her the subject of a cyberbullying attack. Madison Pettis also guest starred in the episode, titled "No Good Reason", which aired on NBC, October 18th 2017.[20] Another Broadway star, Christiane Noll, guest starred in the episode "Unintended Consquences" as Sarah Curtis "After 19 years on the air, I will finally be appearing as a guest star on episode #19006 of Law & Order: SVU! I am really excited because this is my first big guest starring role," Noll told Playbill.[21] Peter Scolari guest starred along with Noll in "Unintended Consequences" as Dr. Dennis Barkley.[22] In October 2017, THR announced Melora Walters and Joanna Going would guest star in a special episode of SVU ("Something Happened"). Walters played the rape victim, Laurel Linwood, who knows she was raped but can't remember what happened. Going played Laurel's sister, Leah, who is brought in to help fill in the blanks.[23]

text: On September 20, 2017, it was announced Sam Waterston will guest star in an upcoming episode of SVU as his Law & Order character, Jack McCoy. Waterston will be re-united with show runner/EP Michael S. Chernuchin, who also held the same position at the time Waterston joined the original series in 1994; Chernuchin is credited as the creator of the McCoy character. This will also mark Waterston's fourth guest appearance on SVU.[24] In the episode "Pathological", Tamara Tunie (M.E. Melinda Warner), Carolyn McCormick (Dr. Elizabeth Olivet), and Jenna Stern (Judge Elana Barth) returned as their respective characters.[25] The episode aired on January 10, 2018.

text: On December 14, 2017, Martin Donovan and Yasmine Al Massri were confirmed to guest star in an episode titled "Flight Risk" based on the Harvey Weinstein sexual abuse allegations.[26] The episode was about sexual harassment in the airline industry and aired on January 17, 2018.

text: Episodes[edit]

text:
No.
overall
No. in
season
Title
Directed by
Written by
Original air date
Prod.
code
U.S. viewers
(millions)

411
1
"Gone Fishin'"
Alex Chapple
Michael Chernuchin
September 27, 2017 (2017-09-27)
1901
5.67[27]

The Special Victims Unit is notified about a fugitive rapist (Will Chase) on the loose in Havana, Cuba. Fin crosses international borders to capture him, which soon causes political controversy when Fin is accused of kidnapping the perp. When all of his victims are reluctant to testify, Benson must count on one victim (Amy Smart) to help put the perp away. Meanwhile, Benson discovers shocking allegations made about her, which eventually leads to her ex-boyfriend and former SVU detective Brian Cassidy returning to her life to investigate her actions and the allegation made against her.

412
2
"Mood"
Michael Pressman
Allison Intrieri
October 4, 2017 (2017-10-04)
1902
5.82[28]

A woman (Saxon Sharbino) reports to SVU that she was raped. At first, the detectives believe her but, after several misleading reports, the detectives soon find themselves in a complicated position, with Rollins and Carisi fighting about whether her story is true and whether the case should be taken to trial. Meanwhile, Cassidy continues his investigation into Benson's personal life regarding the shocking allegations made about her and Benson decides to take action, leading to an extremely shocking discovery and the loss of an old friendship in Benson's life.

413
3
"Contrapasso"
Jean de Segonzac
Richard Sweren
October 11, 2017 (2017-10-11)
1903
5.79[29]

A man (Paul Fitzgerald) is brutally castrated and left for dead in a hotel, but survives the ordeal and the Special Victims Unit soon discover there were three witnesses to the scene, who immediately become suspects in the case. However, the case quickly takes a bizarre twist when the three witnesses make a claim that they are victims from something he did in the past and they were getting revenge. Barba must decide whether to prosecute the women or defend them in the complicated case. Meanwhile, Olivia gets shocking news from Trevor Langan regarding Noah's biological family, revealing that Noah's mother Ellie Porter had been lying about something all this time during the past investigation.

414
4
"No Good Reason"
Martha Mitchell
Julie Martin & Brianna Yellen
October 18, 2017 (2017-10-18)
1904
5.58[31]

The Special Victims Unit is called in to investigate the sudden disappearance of a high school student (Brighton Sharbino). They soon discover that she was the victim of a nasty cyberbullying attack from her fellow peers and best friend (Madison Pettis). When she is finally found, she claims that she was raped by three boys from her school at a party, one being one of her best friends. The case goes well, until the victim becomes reluctant to testify, due to hatred and bullying from her peers, and Benson must convince her to testify. Meanwhile, Sheila Porter attempts to challenge Benson's parenting skills as a mother, which infuriates Benson.

Episode inspired by the events in the Netflix web series 13 Reasons Why.[30]

415
5
"Complicated"
Tricia Brock
Céline C. Robinson
October 25, 2017 (2017-10-25)
1905
5.81[32]

A young woman (Ily Ray) who has been missing for ten years is suddenly found and the cold case into her disappearance is reopened by the Special Victims Unit. However, the detectives become suspicious of her story when several things don't match up and the detectives soon discover a disturbing cold secret kept in the family. Meanwhile, Benson and Sheila both fight against each other for custody of Noah, with Sheila claiming she fears for Noah's safety due to Benson's recent allegations, infuriating Benson and putting them both in an intense and conflicted relationship.

416
6
"Unintended Consequences"
Jonathan Herron
Elizabeth Rinehart
November 8, 2017 (2017-11-08)
1906
4.97[33]

The Special Victims Unit are called to a high end rehab center to investigate the death of a teenage girl, after she was last seen there. Suspicious of the activity going on and the concerning behaviour and reports from some of the clients, Rollins goes undercover in the rehab center as a worker, joining the manager (Anne Corley) in her duties, hoping to get evidence of criminal activity in order to get justice for the murder victim's family. Meanwhile, Benson tries to overcome her doubts about Sheila, after letting her visit Noah for the first time and befriending her.

417
7
"Something Happened"
Alex Chapple
Michael Chernuchin
November 29, 2017 (2017-11-29)
1907
7.07[34]

A rape victim (Melora Walters) who can't remember the details or what happened when she was sexually assaulted visits the Special Victims Unit, distraught and desperate to remember exactly what happened. Benson brings her into an interrogation room to help her remember the details of what happened. However, it quickly becomes intense when the rape victim starts to break down in fear, stress and desperation. In order to help the victim remember what happened, Benson finally decides to tell her a long kept secret from her past that she hasn't told anyone before, in the hopes that the victim will remember what happened and who assaulted her so justice can be served. The case soon takes a shocking twist which reveals a secret long kept from both the victim and her sister (Joanna Going).

418
8
"Intent"
Adam Bernstein
Robert Brooks Cohen & Lawrence Kaplow
December 6, 2017 (2017-12-06)
1908
6.18[35]

The Special Victims Unit are called in after a popular social media star (Gage Golightly) is raped, following a romantic date gone wrong. The detectives discover she posted a hint of who she was dating online for her followers, but the victim's reputation is soon questioned after a text threat is discovered that was subsequently sent to her suspected rapist which could ruin the case. Meanwhile, Benson sets firm ground rules with Sheila about what she can and cannot tell Noah about his past and family background, but eventually, Olivia's worst nightmare comes true when she gets some horrifying news about Noah.

419
9
"Gone Baby Gone"
Jean de Segonzac
Lawrence Kaplow & Elizabeth Rinehart
January 3, 2018 (2018-01-03)
1909
6.23[36]

The Special Victims Unit, along with Deputy Chief William Dodds, start a top priority frantic search for Noah after he is kidnapped while clothes shopping with Sheila at the mall. Benson, frantic, starts to panic, which sends emotions running high amongst the team members. Desperate to have her son safe and back with her, Benson decides to take matters into her own hands and tries to attempt to track down Noah's kidnapper, despite Dodds' orders. However, things eventually become extremely dangerous and Benson's life is soon put in serious danger as things take a shocking twist.

420
10
"Pathological"
Jono Oliver
Brianna Yellen
January 10, 2018 (2018-01-10)
1910
6.06[38]

The Special Victims Unit are called to investigate a sexual assault case involving two disabled children (Conor Tague & Erin Wilhelmi) who attend a special needs school. Through further investigation, the case takes a surprising twist after Rollins discovers a shocking truth when one of the students' medical exam shows that the child's medical disability stems from a surprising source and the case soon turns into one of child abuse in the hands of her mother (Dendrie Taylor). The case soon goes from bad to worse when the abuse case soon turns to murder. Meanwhile, Benson tries to help Noah cope with nightmares after the previous traumatizing events involving himself, Benson and Sheila Porter.

Episode inspired by the Murder of Dee Dee Blancharde[37]

421
11
"Flight Risk"
Michael Pressman
Julie Martin & Allison Intrieri
January 17, 2018 (2018-01-17)
1911
6.21[40]

When a Muslim female pilot (Yasmine Al Massri) locks herself in the cockpit and attempts to return the plane to JFK Airport (nearly causing a crash), she finds herself arrested on suspicion of terrorism. However, when she makes a claim that the captain of the plane (Martin Donovan) was sexually assaulting her and she diverted the plane to avoid contact with him, the Special Victims Unit is called to investigate. Barba eventually convenes with a grand jury to determine the suspected rapists complicity in the crime. Meanwhile, Tutuola takes several steps to ensure that Benson is safe at work, after the previous incident with Sheila Porter.

Episode inspired by the Harvey Weinstein sexual abuse allegations.[39]

422
12
"Info Wars"
Michael Slovis
Richard Sweren & Robert Brooks Cohen
January 31, 2018 (2018-01-31)
1912
5.48[43]

The Special Victims Unit are called to a brutal crime scene after a violent protest in the city results in a controversial female pundit (Rhea Seehorn) getting viciously sexually assaulted. However, with many people in the crowd during the protest, the squad has a hard time catching the victim's assailants. When the case is taken to trial, Barba and Benson both fight with each other after struggling to keep their political opinions about the case quiet and both disagreeing with each other, which leaves the squad clashing over sides in the controversial, violent case and sets tensions rising between the detectives and Barba.

Episode and episode title inspired by actual website InfoWars, with specific main character reference to InfoWars' reporter Millie Weaver.[41][42]

423
13
"The Undiscovered Country"
Alex Chapple
Michael Chernuchin
February 7, 2018 (2018-02-07)
1913
6.64[45]

The Special Victims Unit are called in to investigate after a father (Joe Tapper) kidnaps his mitochondrial DNA depletion syndrome-affected infant. When the father is found, he says he wants his son alive, whereas his wife (Abigail Hawk) wants him put out of his misery, which sends the SVU detectives taking sides in the family's right-to-die case. Barba's interference in the case leads to the entire DA's office being in jeopardy, which results in DA Jack McCoy getting involved and sending Barba to trial for murder, however is found not guilty. Traumatized by the case, Barba quits his job as an ADA and is replaced by former Chicago ADA Peter Stone, who has recently lost his father Benjamin Stone, who was a former ADA previously assigned to the NYPD's Homicide Unit.

Episode inspired by the Charlie Gard case.[44]

424
14
"Chasing Demons"
Fred Berner
Richard Sweren & Allison Intrieri
February 28, 2018 (2018-02-28)
1914
TBD

The Special Victims Unit take a doctor to trial who has been accused of molesting little boys. As the trial is going good, Brian Cassidy testifies but when the doctor’s lawyer suspects Cassidy of being racist, Cassidy loses it, which causes a mistrial. However, when Cassidy turns up to Benson’s apartment with blood on him and Dr. West is found dead after Cassidy visited him, Benson must decide whether Cassidy is guilty of murder or if Cassidy is innocent which he claims, which complicates Rollins’ and Benson’s relationship and sends Stone and Benson’s friendship to a rocky start, all while a Homicide detective investigates Cassidy.

425
15
"In Loco Parentis"[46]
TBA
TBA
March 7, 2018 (2018-03-07)
1915
TBD

426
16
"Dare"[47]
TBA
TBA
March 14, 2018 (2018-03-14)
1916
TBD

427
17
"Send in the Clowns"[48]
TBA
TBA
March 21, 2018 (2018-03-21)
1917
TBD

text: Ratings[edit]

text:
No.
Title
Air date
Rating/share
(18–49)
Viewers
(millions)
DVR
(18–49)
DVR viewers
(millions)
Total
(18–49)
Total viewers
(millions)

1
"Gone Fishin'"
September 27, 2017
1.4/5
5.67[27]
1.0
3.19
2.4
8.83[49]

2
"Mood"
October 4, 2017
1.3/5
5.82[28]
TBD
TBD
TBD
TBD

3
"Contrapasso"
October 11, 2017
1.2/5
5.79[29]
1.0
2.82
2.2
8.61[50]

4
"No Good Reason"
October 18, 2017
1.2/4
5.58[31]
1.0
2.85
2.2
8.45[51]

5
"Complicated"
October 25, 2017
1.2/4
5.81[32]
0.9
2.77
2.1
8.59[52]

6
"Unintended Consequences"
November 8, 2017
1.1/4
4.97[33]
0.9
3.04
2.0
8.01[53]

7
"Something Happened"
November 29, 2017
1.5/5
7.07[34]
1.0
3.08
2.5
10.15[54]

8
"Intent"
December 6, 2017
1.3/5
6.18[35]
0.9
2.68
2.2
8.86[55]

9
"Gone Baby Gone"
January 3, 2018
1.4/5
6.23[36]
TBD
TBD
TBD
TBD

10
"Pathological"
January 10, 2018
1.3/5
6.06[38]
1.0
3.09
2.3
9.15[56]

11
"Flight Risk"
January 17, 2018
1.4/5
6.21[40]
1.0
2.98
2.4
9.17[57]

12
"Info Wars"
January 31, 2018
1.2/5
5.48[43]
1.0
3.01
2.2
8.48[58]

13
"The Undiscovered Country"
February 7, 2018
1.3/5
6.64[45]
1.0
3.17
2.3
9.81[59]

14
"Chasing Demons"
February 28, 2018
TBD
TBD
TBD
TBD
TBD
TBD

15
"In Loco Parentis"
March 7, 2018
TBD
TBD
TBD
TBD
TBD
TBD

16
"Dare"
March 14, 2018
TBD
TBD
TBD
TBD
TBD
TBD

17
"Send In The Clowns"
March 21, 2018
TBD
TBD
TBD
TBD
TBD
TBD