Amino Acid Metabolism
Amino Acid Metabolism (Degradation and Synthesis)
The fates of the carbon skeletons of amino acids after the removal of the α-amino group.
The strategy of amino acid degradation is to transform the carbon skeletons into major metabolic intermediates that can be converted into glucose or oxidized by the citric acid cycle. The conversion pathways range from extremely simple to quite complex. The carbon skeletons of the diverse set of 20 fundamental amino acids are funneled into only seven molecules and these intermediate produced from the metabolism of aminoacid are;
oxaloacetate, α-ketoglutarate, pyruvate, succinyl CoA, acetyl CoA, Fumarate and acetoacetyl CoA.
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Figure 1. overview of metabolic pathways of amino acid,
GLUCOGENIC AND KETOGENIC AMINO ACIDS
Amino acids are grouped into two classes, based on whether or not their carbon skeletons can be converted to glucose:
A. Glucogenic amino acids
Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic or glycogenic. These intermediates are substrates for gluconeogenesis and, therefore, can give rise to the net formation of glucose or glycogen in the liver and glycogen in the muscle.
B. Ketogenic amino acids
Amino acids whose yields either acetoacetate or its precursor, (acetyl CoA or acetoacetyl CoA) are termed ketogenic. Acetoacetate , 3-hydroxybutyrate and acetone all are (ketone body.) Leucine and lysine are the only exclusively ketogenic amino acids found in proteins. Their carbon skeletons are not substrates for gluconeogenesis and, therefore, cannot give rise to the net formation of glucose or glycogen in the liver, or glycogen in the muscle.
Figure 2.CATABOLISM OF THE CARBON SKELETONS OF AMINO ACIDS
The pathways by which amino acids are catabolized are conveniently organized according to which one (or more) of the seven intermediates listed above is produced from a particular amino acid.
A. Amino acids that form oxaloacetate
1.Asparagine is hydrolyzed by asparaginase, liberating ammonia and aspartate
2.Aspartate loses its amino group by transamination to form oxaloacetate (see Figure 3).
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Figure 3. Amino acids that form oxaloacetate
B. Amino acids that form α-ketoglutarate
1 .Glutamine is converted to glutamate and ammonia by the enzyme
Glutaminese Glutamate is converted to α-keto- glutarate by transamination, or through oxidative deamination by glutamate dehydrogenase
2. Proline is oxidized to glutamate
3.Arginine is cleaved by arginase to produce ornithine. [Note: This reaction occurs primarily in the liver as part of the urea cycle
Ornithine is subsequently converted to α-ketoglutarate
4. Histidine is oxidatively deaminated by histidase
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Amino acids that form α-ketoglutarate Figure 4.
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Figure 5. Histidine metabolism
C. Amino acids that form pyruvate
1. Alanine loses its amino group by transamination to form pyruvate
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Figure 6. transamination Alanine to form pyruvate
2. Serine can be converted to glycine and N5,N10-methylenetetra-hydrofolate .Serine can also be converted to pyruvate by serine dehydratase
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4. Cystine
undergoes desulfuration to yield pyruvate.
5. Threonine converted to pyruvate or to α-ketobutyrate, which forms succinyl CoA.
6.Tryptophan converted to pyruvate
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Figure7 .Amino acids that form pyruvate
D. Amino acids that form fumarate
1. Phenylalanine and tyrosine: Hydroxylation of phenylalanine leads to the formation of tyrosine (Figure 20.7). This reaction, catalyzed by
phenylalanine hydroxylase is the first reaction in the catabolism of phenylalanine. Thus, the metabolism of phenylalanine and tyrosine merge, leading ultimately to the formation of fumarate and acetoacetate. Phenylalanine and tyrosine are, therefore, both glucogenic and ketogenic.
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E. Amino acids that form succinyl CoA:
Succinyl CoA is a point of entry for some of the carbon atoms of methio-nine, isoleucine, and valine. Propionyl CoA and then methylmalonyl CoA are intermediates in the breakdown of these three nonpolar amino acids The mechanism for the interconversion of propionyl CoA and methylmalonyl CoA. This pathway from propionyl CoA to succinyl CoA is also used in the oxidation of fatty acids that have an odd number of carbon atoms
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Figure 8. Amino acids that form succinyl CoA
Methionine metabolism
Methionine is one of four amino acids that form succinyl CoA.
Methionine is converted to S-Adenosylmethionine (SAM) by an ATP-dependent reaction. SAM serves as a methyl group donor in various synthetic reactions. After donation of the methyl group from SAM, S-adenosyl homocysteineis formed and The resulting adenosylhomocysteine is hydrolyzed to homocysteine, which may be catabolized via a complex pathway to cysteine and succinyl-CoA.
Or methionine may be regenerated from homocysteine by methyl transfer from N5-methyl-tetrahydrofolate, via a methyltransferase enzyme that utilizes B12 as prosthetic group. The methyl group is transferred from tetrahydrofolate to B12 to homocysteine( cobalamin recharged from N5-methyl-THF and this called Activated Methyl Cycle.of methionine .
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Activated Methyl Cycle.of methionine The methyl group of methionine is activated by the formation of S-adenosylmethionine
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Methionine Metabolism
F. Other amino acids that form succinyl CoA
Degradation of valine, isoleucine, and threonine also results in the production of succinyl TCA cycle intermediate and glucogenic compound.
1. Valine and isoleucine are branched-chain amino acids that yield succinyl CoA (Figure 20.10).
2. Threonine is dehydrated to α-ketobutyrate, which is converted to propionyl CoA, the precursor of succinyl CoA [Note:Threonine can also be converted to pyruvate.]
G. Amino acids that form acetyl CoA or acetoacetyl CoA
Leucine, isoleucine, lysine, and tryptophan form acetyl CoA or acetoacetyl CoA directly, without pyruvate serving as ketogenic
As mentioned previously, phenylalanine and tyrosine also give rise to acetoacetate during their catabolism. Therefore,there are a total of six ketogenic amino acids.
The branched-chain amino acids, isoleucine, leucine, and valine
1. Leucine is exclusively ketogenic in its catabolism, forming acetylCoAand^acetoacetate
Lysine, an exclusively ketogenic amino acid
Isoleucine is both ketogenic and glucogenic
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