Amino Acid Degradation and Synthesis . UNIT IV: Nitrogen Metabolism. I. Overview . The catabolism of the amino acids found in proteins involves the removal of α-amino groups, followed by the breakdown of the resulting carbon skeletons.
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A. Glucogenic amino acids
A. Amino acids that form oxaloacetate
- Some rapidly dividing leukemic cells are unable to synthesize sufficient asparagine to support their growth.
- This makes asparagine an essential amino acid for these cells, which therefore require asparagine from the blood.
- Asparaginase, which hydrolyzes asparagine to aspartate, can be administered systemically to treat leukemic patients.
- Asparaginase lowers the level of asparagine in the plasma and, therefore, deprives cancer cells of a required nutrient.]
1. Glutamine is converted to glutamate and ammonia by the enzyme glutaminase.
2. Proline: This amino acid is oxidized to glutamate.
3. Arginine: This amino acid is cleaved by arginase to produce ornithine.
[Note: This reaction occurs primarily in the liver as part of the urea cycle.]
1. Alanine: This amino acid loses its amino group by transamination to form pyruvate.
2. Serine: This amino acid can be converted to glycine and N5,N10-methylenetetrahydrofolate.
3. Glycine: This amino acid can either be converted to serine by addition of a methylene group from N5,N10-methylenetetrahydrofolic acid (see Figure 20.6A), or oxidized to CO2 and NH3.
5. Threonine: This amino acid is converted to pyruvate or to α-ketobutyrate, which forms succinyl CoA.
1. Phenylalanine and tyrosine: Hydroxylation of phenylalanine leads to the formation of tyrosine (Figure 20.7).
2. Inherited deficiencies: Inherited deficiencies in the enzymes of phenylalanine and tyrosine metabolism lead to the diseases phenylketonuria, and alkaptonuria, and the condition of albinism.
2. Activated methyl group: The methyl group attached to the tertiary sulfur in SAM is “activated,” and can be transferred to a variety of acceptor molecules, such as norepinephrine in the synthesis of epinephrine (see p. 286).
Figure 20.9 Association between cardio-vascular disease mortality and total plasma homocysteine.
Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6
on clinical outcome after coronary angioplasty. [Note: Balloon angioplasty is a
noninvasive procedure in which a balloon-tipped catheter is introduced into a diseased
blood vessel. As the balloon is inflated, the vessel opens further, allowing for placement
of a stent and improved flow of blood.]
2. Threonine: This amino acid is dehydrated to α-ketobutyrate, which is converted to propionyl CoA and then to succinyl CoA.
[Note: Threonine can also be converted to pyruvate.]
1. Leucine: This amino acid is exclusively ketogenic in its catabolism, forming acetyl CoA and acetoacetate (see Figure 20.10).
3. Lysine: An exclusively ketogenic amino acid, this amino acid is unusual in that neither of its amino groups undergoes transamination as the first step in catabolism.
4. Tryptophan: This amino acid is both glucogenic and ketogenic because its metabolism yields alanine and acetoacetyl CoA.
2. Oxidative decarboxylation: Removal of the carboxyl group of the α-keto acids derived from leucine, valine, and isoleucine is catalyzed by a single multienzyme complex, branched-chain α-keto acid dehydrogenase complex.
4. End products: The catabolism of isoleucine ultimately yields acetyl CoA and succinyl CoA, rendering it both ketogenic and glucogenic.
Figure 20.11 Summary of the interconversions and uses of the carrier, tetra-hydrofolate.
Figure 20.12 Formation of alanine, aspartate, and glutamate from the corresponding α-keto acids.
D. Serine, glycine, and cysteine
3. Cysteine: This amino acid is synthesized by two consecutive reactions in which homocysteine combines with serine, forming cystathionine, which, in turn, is hydrolyzed to α-ketobutyrate and cysteine (see Figure 20.8).
Figure 20.13 Incidence of inherited diseases of amino acid metabolism. [Note: Cystinuria is the most common genetic error of amino acid transport.]
Figure 20.14 Summary of the metabolism of amino acids in humans. Genetically determined enzyme deficiencies are summarized in white boxes. Nitrogen-containing compounds derived from amino acids are shown in small, yellow boxes. Classification of amino acids is color coded: Red = glucogenic; brown = glucogenic and ketogenic; green = ketogenic. Compounds in BLUE ALL CAPS are the seven metabolites to which all amino acid metabolism converges.
Screening of newborns for a number of the amino acid disorders using a few drops of blood is possible; however, exactly which disorders are screened for currently varies from state to state, and only phenylketonuria screening is mandated by all states.
Figure 20.15 A deficiency in phenylalanine hydroxylase results in the disease phenylketonuria (PKU).
Figure 20.16 Biosynthetic reactions involving amino acids and tetrahydrobiopterin.
Figure 20.17 Pathways of phenylalanine metabolism in normal individuals and in patients with phenylketonuria
3. Treatment: The disease is treated with a synthetic formula that contains limited amounts of leucine, isoleucine, and valine—sufficient to provide the branched-chain amino acids necessary for normal growth and development without producing toxic levels.
Figure 20.20 Patient with oculocutaneous albinism, showing white eyebrows and lashes.