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We have seen before that, during digestion in the gut, proteins are broken down to their constituent amino acids. Proteins contain twenty standard amino acids.
Table of contents
Overview of Amino Acid Metabolism. Video transcript - [Instructor] In this video, I wanna provide you with a crash course overview of amino acid metabolism. And, specifically, I wanna focus on the catabolism of amino acids and how that catabolism allows us to produce ATP inside of ourselves. Now, compared to carbohydrate catabolism and fatty acid catabolism, recall the pathways of glycolysis and fatty acid oxidation.
So that's why I think that amino acid metabolism doesn't usually get its fair share of airtime, compared to processes like glycolysis and fatty acid oxidation. And to do that, let's go ahead and follow what happens to amino acids in the fed, as well as the fasted states of our body. Now, fed refers to our body's state right after, immediately after eating a meal. And, remember, that in terms of hormones, the hormone that's going to be elevated is going to be insulin, which is elevated in response to higher blood glucose levels, immediately following a meal, and levels of the hormone glucagon are going to be decreased.
Now, of course, this is going to be opposite several hours after a meal, which we called the fasted state, in which the levels of insulin will be decreased and, of course, in response to low blood glucose levels, the levels of glucagon in our body will start to rise along with a couple of other hormones as well.
But these are the two, or two at least, big hormones that regulate the bulk of metabolism in our body. Now, starting with the fed state, let's start at the beginning of this story. Recall that we ingest proteins from our food and those proteins are broken down into amino acids inside of our small intestine. And just as a side note, you might hear the terms essential and non-essential amino acids used, especially in medical literature.
And what this simply refers to is that essential amino acids are those amino acids, of the 20 that we know of, that our body cannot synthesize and so we must, somehow, get these in our diet. Whereas non-essential amino acids can be actually synthesized in our body and we don't need them as part of our diet. But, getting back to these amino acids, once they're broken down in the small intestine, they travel via the blood stream directly to the liver, just like glucose.
Now, once the amino acids have made it to the liver, several things can happen. The liver can use these amino acids directly for protein synthesis. And, of course, recall that the storage, the ultimate storage forms of these two molecules are gonna be glycogen, in the case of glucose, which is stored in the liver mainly, and, for fatty acids, we store these as triacylglycerides in our adipose tissue.
So how did this conversion from amino acids to glucose and fatty acids happen, you might ask? Well, remember that the precursor for glucose, or I should say precursors, can be pyruvate as well as oxaloacetate. And, for fatty acids, the main precursor for fatty acid synthesis is the molecule acetyl-CoA. And, as a relevant side note, I wanna point out that acetyl-CoA happens to be in equilibrium with another molecule in the cell called acetoacetyl-CoA.
Protein anabolism is the process by which protein are formed from amino acids anabolic amino acid synthesis. Protein catabolism is the process by which proteins are broken down to their amino acids. This is also called proteolysis. This can be followed by further amino acid degradation. From Wikipedia, the free encyclopedia. Metabolism of amino acids- bimolecular ping pong mechanism of transamination.
Metabolism , catabolism , anabolism. Metabolic pathway Metabolic network Primary nutritional groups. Pentose phosphate pathway Fructolysis Galactolysis. Although it would be assumed that increased intake of vitamin B 12 should lead to increased conversion of homocysteine to methionine and thus, reduced levels of circulating homocysteine, controlled studies have shown that this does not occur.
S-adenosylmethione abbreviated SAM or AdoMet , synthesized as described in the previous section, is utilized in a wide array of methyl transfer reactions involving nucleic acids, lipids, proteins, neurotransmitters, and small molecules. The resultant SAH is catabolized to adenosine and homocysteine through the action of adenosylhomocysteinase also called S-adenosylhomocysteine hydrolase which is encoded by the AHCY gene. The AHCY gene is located on chromosome 20q Mutations in the AHCY gene are one of the causes of hypermethioninemia.
The role of SAM in nucleotide and protein methylation contributes to several epigenetic processes and points to the role of nutritional components, in this case methionine, in the control of gene expression. These latter mRNA methylation events represent important posttranscriptional mechanisms for the regulation of gene expression. Numerous SAM-dependent methyltransferases are involved in the methylation of histone proteins which represents another mode of epigenetic regulation of gene expression.
These methyltransferases all utilize SAM as the methyl donor and incorporate the methyl group onto lysine residues, arginine residues, and histidine residues in proteins. Several histone lysine and histone arginine N -methyltransferases have been identified including all of the HMT histone lysine methyltransferase gene family enzymes and the PRMT protein arginine methyltransferase gene family enzymes.
Humans express 34 genes that encode protein lysine methyltransferases and nine genes that encode protein arginine methyltransferases. Many of the proteins that are targets for enzymes of the PRMT family are involved in the processes of signal transduction or regulation of transcription. In addition to members of the histone protein family and transcription factor family, numerous other proteins are subject to either lysine or arginine methylation.
Additional enzymes that utilize SAM as a methyl donor are involved in the modification of proteins that serve functions in diverse processes such as protein damage repair, protein stability, and protein function. The enzyme identified as protein-L-isoaspartate D-aspartate O -methyltransferase encoded by the PCMT1 gene is required for the repair of deamidated aspartate and asparagine residues in proteins.
The function of the enzyme, isoprenylcysteine carboxyl methyltransferase encoded by the ICMT gene is to methylate the cysteine residues in the C-terminus of proteins following their prenylation. Humans express three genes that catalyze the SAM-dependent cysteine methylation reaction on prenylated proteins with the ICMT gene being the most abundantly expressed. The synthesis of the diphthamide residue found on His in human translation elongation factor eEF2 requires a methylation step involving SAM as the methyl donor.
Numerous reaction pathways involved in the synthesis of small molecules, as well as the synthesis and catabolism of neurotransitters involve enzymes that are SAM-dependent methyltransferases.
Fat and protein metabolism
These methyltransferases are classified as either N -methyltransferases or O -methyltransferases dependent on whether the acceptor of the methyl group is nitrogen or an oxygen, respectively. The conversion of serotonin to melatonin requires the enzyme acetylserotonin O -methyltransferase encoded by the ASMT gene. The catabolism of the catecholamines , epinephrine, norepinephrine, and dopamine involves the SAM-dependent enzyme catechol O -methyltransferase encoded by the COMT gene. The catabolism of histamine occurs either through oxidation or methylation. Lipid metabolism is another important process that involves SAM-dependent methylation.
The conversion of phosphatidylethanolamine PE to phosphatidylcholine PC requires the enzyme phosphatidylethanolamine N -methyltransferase encoded by the PEMT gene which carries out three successive SAM-dependent methylation reactions. This reaction is a critically important reaction of membrane lipid homeostasis. Lipid synthesis and remodeling is important in all cell membranes but is particularly critical in the homeostasis of the myelin sheath protecting neurons in the nervous system.
Reduced capacity to carry out the methionine synthase reaction, due to nutritional or disease mediated deficiency of vitamin B 12 , results in reduced SAM production. In turn, reduced levels of SAM in the brain are a contributor to the neural degeneration i. The metabolism and detoxification of numerous xenobiotic compounds is also known to require SAM-dependent methyltransferase family enzymes.
The anti-cancer drugs of the thiopurine class, such as 6-mercaptopurine, are metabolized by the enzyme thiopurine S-methyltransferase which is encoded by the TPMT gene. Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine.
Phenylalanine hydroxylase more specifically phenylalanine 4-hydroxylase is a mixed-function monooxygenase that is one of three enzymes belonging to the biopterin-dependent aromatic amino acid hydroxylase AAAH family. Phenylalanine hydroxylase is encoded by the PAH gene located on chromosome 12q22—q The required biopterin is in the form of tetrahydrobiopterin often designated BH 4 or H 4 B.
The other two enzymes in this family are tyrosine hydroxylase and tryptophan hydroxylase. The PCBD1 gene is located on chromosome 10q Dihydrobiopterin is then converted to tetrahydrobiopterin by the NADH-dependent enzyme commonly referred to as dihydropteridine reductase. Human dihydropteridine reductase is produced by the quinoid dihydropteridine reductase gene symbol: QDPR located on chromosome 4p Biosynthesis of tyrosine from phenylalanine. Phenylalanine serves as the precursor for tyrosine. The conversion of phenylalanine to tyrosine can also be considered the first step in the catabolism of phenylalanine as this conversion reaction is necessary to catabolize phenylalanine.
Missing or deficient phenylalanine hydroxylase results in hyperphenylalaninemia. The most widely recognized hyperphenylalaninemia and most severe is the genetic disease known as phenlyketonuria PKU. Untreated PKU leads to severe mental retardation, however, the precise mechanism by which this enzyme deficiency leads to the severe neural degeneration is not fully understood. One theory suggests that the accumulation of phenylalanine interferes with the transport of tyrosine into the brain.
A reduction in brain tyrosine levels would then result in reduced synthesis of the neurotransmitters dopamine and norepinephrine. This absence of 2-oxoglutarate in the brain shuts down the TCA cycle and the associated production of aerobic energy. Although both theories are plausible no direct evidence for either has been demonstrated. The product of phenylalanine transamination, phenylpyruvic acid, is reduced to phenylacetate and phenyllactate, and all 3 compounds appear in the urine. The presence of phenylacetate in the urine imparts a "mousy" odor.
If the problem is diagnosed early, the addition of tyrosine and restriction of phenylalanine from the diet can minimize the extent of mental retardation. Because of the requirement for tetrahydrobiopterin in the function of phenylalanine hydroxylase, mutations in the PCBD1 gene or the QDPR gene can manifest with hyperphenylalaninemia.
At least nine different mutations in the PCBD1 gene have been found to be associated with inherited tetrahydrobiopterin deficiency. However, the mutations in PCBD1 are not associated with significant pathology. It is thought that other enzymes can compensate for the reduced activity of PCBD1. Because the activity of the QDPR gene encoded enzyme is also involved in the functions of the tyrosine hydroxylase and tryptophan hydroxylase enzymes, mutations in the QDPR gene present as atypical hyperphenylalaninemias but are also associated with the potential for microcephaly, hypotonia, mental retardation, and convulsions due to neurotransmitter synthesis deficits.
In these atypical hyperphenylalaninemias, that result from QDPR mutations, restriction of phenylalanine from the diet has no therapeutic benefits. While ornithine is not one of the 20 amino acids used in protein synthesis, it plays a significant role as the acceptor of carbamoyl phosphate in the urea cycle.
Ornithine serves an additional important role as the precursor for the synthesis of the polyamines. The production of ornithine from glutamate is important when dietary arginine, the other principal source of ornithine, is limited. The synthesis of ornithine from glutamate occurs only in the intestines. Mutations in the ALDH18A1 gene result is a disorder charaterized by hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia. This disorder is also associated with CNS degeneration, connective tissue disruption, and cataract formation.
Ornithine aminotransferase is encoded by the OAT gene located on chromsome 10q26 and is composed of 12 exons that generate two alternatively spliced mRNAs. Ornithine production occurs from the semialdehyde compound via a simple glutamate-dependent transamination, producing ornithine. The PYCR1 gene is located on chromosome 17q Synthesis of ornithine and proline. The main pathway to de novo biosynthesis of serine starts with the glycolytic intermediate 3-phosphoglycerate.
An NADH-linked dehydrogenase 3-phosphoglycerate dehydrogenase converts 3-phosphoglycerate into a keto acid, 3-phosphohydroxypyruvate, suitable for subsequent transamination. The aminotransferase, phosphoserine aminotransferase 1, utilizing glutamate as a donor, produces 3-phosphoserine, which is converted to serine by phosphoserine phosphatase. The phosphoserine phosphatase gene symbol: PSPH is located on chromsome 7p WBS is associated with multiple organ system involvement typically showing supravalvular aortic stenosis SVAS , mental retardation, and distinctive facial features.
Phosphoglycerate dehydrogenase is encoded by the PHGDH gene which is located on chromosome 1p12 and is composed of 17 exons that generate a protein of amino acids. Phosphoserine aminotransferase 1 is encode by the PSAT1 gene located on chromosome 9q The PSPH gene is composed of 12 exons that encode a amino acid protein. As indicated below, serine can be derived from glycine and visa versa by a single step reaction that involves serine hydroxymethyltransferase SHMT; also called glycine hydroxymethyltransferase and tetrahydrofolate THF.
Indeed, the interconversion of serine and glycine via the involvement of THF represents the major pathway for the generation of N 5 , N 10 -methylene-THF which of a member of the active pool of folate derivatives. N 5 , N 10 -methylene-THF is required for purine nucleotide and thymine nucleotide biosynthesis. Humans express two serine hydroxymethyltransferase genes, one is a cytosolic enzyme while the other is located in the mitochondria.
The cytosolic enzyme is derived from the SHMT1 gene located on chromosome 17p The mitochondrial enzyme is derived from the SHMT2 gene located on chromosome 12q12—q14 which is composed of 14 exons that generate five altrernatively spliced mRNAs that encode three distinct isoforms of the enzyme. The location of the SMHT1 gene 17p One of the major functions of the SHMT2 encoded enzyme is in mitochondrial thymidylate synthesis pathway via its role in glycine and tetrahydrofolate metabolism.
Reactions of serine biosynthesis. Serine can be derived from the glycolytic intermediate, 3-phosphoglycerate, in a three-step reaciton pathway. The last step in the reaction pathway is catalyzed by phosphoserine phosphatase PSPH. The main pathway to glycine is a one-step reversible reaction catalyzed by serine hydroxymethyltransferase SHMT.
This enzyme is a member of the family of one-carbon transferases and is also known as glycine hydroxymethyltransferase. This reaction involves the transfer of the hydroxymethyl group from serine to the cofactor tetrahydrofolate THF , producing glycine and N 5 , N 10 -methylene-THF.
Amino acid metabolism
As pointed out in the previous section, there are mitochondrial and cytosolic versions of serine hydroxymethyltransferase. The major glycine biosynthetic enzyme is the cytosolic form of SHMT. Glycine is involved in many anabolic reactions other than protein synthesis including the synthesis of purine nucleotides , heme , glutathione, creatine and serine. In addition, glycine functions in the central nervous system as an inhibitory neurotransmitter where it participates in regulating signals that process motor and sensory information that permit movement, vision and audition.
Glycine is co-released with GABA which is the primary inhibitory neurotransmitter.
The GlyR is a ligand-gated ionotropic receptor that is a chloride channel. In addition to glycine, the GlyR can be activated by several other small amino acids such as alanine and taurine. Glycine is also involved in the modulation of excitatory neurotransmission exerted via glutamate binding to N -methyl-D-aspartate NMDA type glutamate receptors. Glutaminase is an important kidney tubule enzyme involved in the process of renal ammoniagenesis. Glutaminase activity is present in many other tissues in addition to the kidney, such as the liver, small intestine, and neurons where its role is nearly as significant as it is within the kidney tubule.
Protein metabolism - Wikipedia
The GLS gene is located on chromosome 2q32—q34 and is composed of 24 exons that undergo alternative splicing to yield several mRNAs generating two isoforms of the enzyme. GLS encoded kidney-type glutaminase is a protein of amino acids and GLS encoded glutaminase C is a protein of amnio acids.
Asparaginase see above is also widely distributed within the body, where it converts asparagine into ammonia and aspartate. Aspartate can serve as an amino donor in transamination reacions yielding oxaloacetate, which follows the gluconeogenic pathway to glucose. Glutamate and aspartate are important in collecting and eliminating amino nitrogen via glutamine synthetase and the urea cycle , respectively. The catabolic path of the carbon skeletons involves simple 1-step aminotransferase reactions that directly produce net quantities of a TCA cycle intermediate.
Alanine is also important in intertissue nitrogen transport as part of the glucose-alanine cycle see above that delivers waste nitrogen from skeletal muscle to the liver where it can be incorporated into urea. The alanine catabolic pathway involves a simple aminotransferase reaction that directly produces pyruvate. The transamination is carried out by alanine transaminase, ALT also called alanine aminotranserase. Generally, the pyruvate produced from alanine has two distinct fates that are controlled by the energy demands of the liver and the metabolic needs of the organism as a whole.
Altrenatively, during the fasted state when blood glucose levels are low, the pyruvate is diverted into the gluconeogenic pathway so that the liver can release glucose to the blood. This makes alanine a glucogenic amino acid. The catabolism of arginine begins within the context of the urea cycle.
It is ultimately hydrolyzed to urea and ornithine by arginase. The dehydrogenase is encoded by the ALDH4A1 gene located on chromosome 1p36 and is composed of 17 exons that generate three alternativley spliced mRNAs, two of which encode the same protein. Proline catabolism involves a two-step process that is essentially a reversal of its synthesis process outlined above. Therefore, ornithine and proline are both glucogenic. Since arginine is metabolized to urea and ornithine, and the resulting ornithine is a glucogenic precursor, arginine is also a glucogenic amino acid.
Catabolism of arginine, ornithine, and proline. The catabolism of ornithine and proline is essentially a reversal of their synthesis from glutamate. In some tissues arginine serves as the precursor for nitric oxide NO production via the action of nitric oxide synthases NOS. The citrulline byproduct of the NOS reaction can feed back into arginine synthesis via the hepatic urea cycle enzymes argininosuccinate synthetase ASS1 and argininosuccinate lyase ASL.
Arginine also serves as the precursor for creatine synthesis and, therefore, arginine can be excreted in the urine as creatine byproduct, creatinine. The cycling of citrulline back to arginine involves the urea cycle enzymes, argininosuccinate synthetase ASS1 and argininosuccinate lyase ASL. The catabolism of serine in humans involves the conversion of serine to glycine and then glycine oxidation to CO 2 and NH 3 , with the production of two equivalents of N 5 , N 10 -methyleneTHF, as was described above in the section on glycine biosynthesis.
Serine can be catabolized back to the glycolytic intermediate, 3-phosphoglycerate, by a pathway that is essentially a reversal of serine biosynthesis, however, the enzymes are different. There are at least three pathways for threonine catabolism that have been identified in yeasts, insects, and vertebrates including mammals. Therefore, it is presumed that this is the predominant threonine catabolizing pathway in humans. The enzymes required for this conversion are propionyl-CoA carboxylase, methylmalonyl-CoA epimerase, and methylmalonyl-CoA mutase, respectively.
This propionyl-CoA conversion pathway is also required for the metabolism of the amino acids valine, isoleucine, and methionine see below , and odd-chain fatty acids. For this reason this three-step reaction pathway is often remembered by the mnemonic as the VOMIT pathway, where V stands for valine, O for odd-chain fatty acids, M for methionine, I for isoleucine, and T for threonine.
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Propionyl-CoA carboxylase functions as a heterododecameric enzyme subunit composition: Mutations in the MUT gene are one cause of the methylmalonic acidemias. The second pathway of threonine catabolism utilizes serine hydroxymethyltransferase SHMT. As indicated above in the Glycine Biosynthesis section, this enzyme belongs to a family of one-carbon transferases and is alternatively named glycine hydroxymethyltransferase or threonine aldolase.
The products of this reaction are acetyl-CoA and glycine. Thus, via this catabolic pathway threonine yields ketogenic and glucogenic byproducts. In humans it appears that threonine aldolase is actually encoded by a non-functional pseudogene, whereas in other mammals and vertebrates e. The 2-aminoketobutyrate is either converted to acetyl-CoA and glycine, via the action of 2-aminoketobutyrate coenzyme A ligase also called glycine C-acetyltransfease , or it can spontaneously degrade to aminoacetone which is converted to pyruvate. The threonine dehydrogenase gene in humans appears to be non-functional due to the incorporation of three inactivating mutations.
Nevertheless, the main glycine catabolic pathway leads to the production of CO 2 , ammonia, and one equivalent of N 5 , N 10 -methyleneTHF by the mitochondrial enzyme, glycine dehydrogenase decarboxylating which is also called the glycine cleavage complex, GCC. The GCC is composed of four mitochondrial proteins encoded by four genes.
The protein components of the GCC are the actual glycine dehydrogenase subunit identified as the P subunit: The P subunit is encoded by the GLCD gene located on chromosome 9p22 and is composed of 25 exons that encode a protein of amino acids. The T subunit aminomethyltransferase is encoded by the AMT gene located on chromosome 3p The L subunit is encoded by the DLD gene located on chromosome 7q31—q32 and is composed of 14 exons that generate multiple alternatively spliced mRNAs.
The DLD encoded protein is also found as a subunit of several other important dehydrogenase complexes: Deficiencies in the H, P, or T proteins results in glycine encephalopathy which is characterized by nonketotic hyperglycinemia. These gene defects result in severe mental retardation that is due to highly elevated levels of glycine in the CNS. There are several pathways for non-protein disposition of cysteine that include both metabolism and catabolism.
The major cysteine catabolic pathway in humans occurs via the action of cysteine dioxygenase type 1 gene symbol: CDO1 oxidizes the sulfhydryl group of cysteine to sulfinate, producing the intermediate cysteine sulfinate. The CDO1 gene is located on chromosome 5q The enzyme sulfite oxidase gene symbol: SUOX then catalyzes the conversion of sulfite to sulfate. The SUOX gene is located on chromosome 12q The enzyme cysteine desulfurase encoded by the NFS1 gene is another important enzyme associated with cysteine catabolism.
Cysteine desulfurase removes the sulfur from cyteine yielding alanine. The sulfur remains associated with cysteine desulfurase and is subsequently transferred to numerous enzymes that possess iron-sulfur clusters for their activity. Cysteine desulfurase is a member of the pyridoxal phosphate B 6 -dependent aminotransferase family. The NFS1 gene is located on chromosome 20q The use of these alternative translational start sites generates mitochondrial and cytoplasmic or nuclear forms of the enzyme.
Other than protein, the most important metabolic products derived from cysteine are glutathione GSH , the bile salt modifying compound, taurine , and as a source of the sulfur for coenzyme-A synthesis. Taurine is used to form the bile acid conjugates taurocholate and taurochenodeoxycholate. Taurine synthesis occurs primarily in the liver since this is the only bile acid synthesizing tissue in the body However, taurine can be transported to the blood and disseminated to other tissues. Taurine is derived from the cysteine catabolism intermediate, cysteine sulfinate.
Cysteine sulfinate is converted to hypotaurine by the rate-limiting enzyme in taurine synthesis, cysteine sulfinic acid decarboxylase, CSAD also called sulfinoalanine decarboxylase. The CSAD gene is located on chromosome 12q Oxidation of hypotaurine to taurine is thought to occur spontaneously, i. Pathways of cysteine catabolism. Catabolism of cysteine is responsible for the release and or transfer of the sulfur from this amino acid.
The catabolism of cysteine can also involve a metabolic pathway as is the case for taurine synthesis. Cysteine catabolism and taurine synthesis both begin with the oxidation to cysteine sulfinic acid catalyzed by cysteine dioxygenase. Cysteine sulfinate is converted to taurine via the action of cysteinesulfinate decarboxylase.
Catabolism of cysteine sulfinate to sulfate ion first involves a transamination that releases 3-sulfinpyruvate that spntaneously decomposes to bisulfite ion and pyruvate.
The transaminase responsible for this reaction is the soluble form of aspartate transaminase which is encoded by the GOT1 gene. The bisulfite ion is in ionic equilibrium with sulfite ion which is then converted to the sulfate ion via the action of sulfite oxidase. Both thiocysteine and thiosulfate can be used by sulfurtransferases to incorporate sulfur into cyanide ion, CN — , thereby detoxifying the cyanide to thiocyanate.
These sulfurtransferase enzymes contain domains called rhodanese domains since they were first identifed in a mitochondrial enzyme that was originally called rhodanese thiosulfate sulfurtransferase, TST. Another rhodanese domain-containing enzyme that is located in the cytosol is called mercaptopyruvate sulfurtransferase MPST. One of the important uses of the sulfate that is derived from the catabolism of cysteine is as a precursor for the formation of 3'-phosphoadenosine-5'-phosphosulfate , PAPS. PAPS is used for the transfer of sulfate to biological molecules such as the sugars of the glycosphingolipids.
Two-step reaction for synthesis of PAPS. The clinical significance of methylmalonyl-CoA mutase in this pathway is that it is one of only two enzymes that requires a vitamin B 12 -derived co-factor for activity. The other B 12 -requiring enzyme is methionine synthase see the Cysteine Synthesis section above. This propionyl-CoA conversion pathway is also required for the metabolism of the amino acids valine, isoleucine, and threonine and fatty acids with an odd number of carbon atoms.
Mutations in the MUT gene are one of the causes of the methylmalonic acidemias. Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine. Under these conditions accumulated homocysteine is remethylated to methionine, using N 5 -methyl-THF as the methyl donor. This group of essential amino acids is identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet.
The catabolism of all three amino acids occurs in most cells but at highest rates in skeletal muscle. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. Humans express two genes that encode BCAT activity. The BCAT1 gene is located on chromosome 12p BCAT1 isoform 1 is a amino acid protein. BCAT1 isoform 2 is a amino acid protein. BCAT1 isoform 3 is a amino acid protein. BCAT1 isoform 4 is a amino acid protein. BCAT1 isoform 5 is a amino acid protein. The BCAT2 gene is located on chromosome 19q The isoform b protein is found in the cytosol.
BCAT2 isoform c is a amino acid protein. Expression of the BCAT1 gene is restricted to only a few tissues types. Expression of BCAT2 is widely distributed among numerous tissues. Although detectable in the fetal liver, the adult liver does not express either BCAT gene. The metabolism of the branched-chain amino acids is critical to overall nitrogen homeostasis in the brain and to the maintenance of proper levels of the excitatory neurotransmitter, glutamate. Within the brain different populations of cells express predominantly BCATc while others express predominantly BCATm and this differential distribution is what is important in overall neuronal nitrogen homeostasis.
Subsequently the metabolic pathways diverge, producing many intermediates. The BCKD complex is one of three dehydrogenase complexes whose vitamin-derived cofactor requirements can be remembered by the mnemonic: The other two dehydrogenase complexes are the PDHc and the 2-oxoglutarate dehydrogenase complexes associated with the TCA cycle. The BCKD complex is a multimeric enzyme composed of three catalytic subunits.
The E2 portion is a dihydrolipoamide branched-chain transacylase composed of 24 lipoic acid-containing polypeptides.