this chapter looked at the synthesis and degradation of different amino acids (put in bold). first it introduced the cofactors involved in these reactions: transamination reactions (such as the reaction involving glutamate introduced in chapter 38) require pyridoxal phosphate (PLP), which bonds its aldehyde carbon to the amino nitrogen and allows for different reactions to occur. FH4 is another cofactor that is involved in one carbon exchanges. BH4 is a cofactor that is involved in ring hydroxylations.
there are several amino acids that can be derived from the glycolytic intermediate, 3-phosphoglycerate. these include serine, cysteine, and glycine. serine is formed by oxidation, transamination to phosphoserine, then removal of the phosphate to form serine. it degrades in a separate pathway to form pyruvate. serine can then be converted to glycine in a reaction that involves both PLP and FH4. cysteine is also derived from serine- serine combines with homocysteine to form cystathione, which forms cysteine (and also succinyl CoA by way of alpha-keto butyrate- to be explained later).
amino acids can also be synthesized to TCA cycle intermediates. in particular, oxaloacetate and alpha-ketoglutarate. as we saw in the urea cycle, oxaloacetate can be transaminated to aspartate, which can be further converted into asparagate. alpha-ketoglutarate can be converted to glutamate in the glutamate dehydrogenase reaction. glutamate can then be converted to glutamine, or it can be converted to glutamate 5-semialdehyde. this compound can be converted to proline, or ornithine. ornithine can then be used to fuel the urea cycle, which produces arginine.
there are also several amino acids that can supply TCA cycle intermediates (an anaplerotic reaction); in particular, the intermediate succinyl CoA. the first was mentioned above- the homocysteine that reacts with serine to form cysteine actually is derived from methionine. in the last step of the cysteine synthesis pathway, the intermediate cystathione cleaves into cysteine and alpha-ketobutyrate, which is converted into propionyl CoA, and ultimately succinyl CoA.
valine and isoleucine are two branched chain amino acids that can replenish succinyl CoA. they are both transaminated into keto acids, then oxidatively decarboxylated into acyl CoA. these are oxidized in a way similar to fatty acid beta oxidation, ultimately producing FADH2, NADH, and propionyl CoA, which is converted to succinyl CoA.
finally, there are amino acids which are "ketogenic"- they produce ketone bodies, either acetyl CoA or acetoacetate, in their degradation. this includes leucine, isoleucine, tyrosine, phenylalanine, threonine, and tryptophan. isoleucine, as mentioned above, produces both succinyl CoA and acetyl CoA in its degradation, whereas leucine only produces acetyl CoA. phenylalanine is converted to tyrosine, which then produces acetoacetate and fumarate in its degradation. finally, tryptophan is an amino acid that produces formate, acetyl CoA, and alanine in its degradation.
questions
cofactors...
1. what are the three cofactors involved in amino acid metabolism?
2. how does pyridoxal phosphate aid in amino acid reactions?
3. how is FH4 involved in amino acid reactions? what is it derived from?
4. how is BH4 involved in amino acid reactions?
amino acids derived from glycolysis...
5. what are the amino acids derived from intermediates of glycolysis?
6. describe the synthesis of serine from glycolytic intermediates.
7. describe the degradation of serine.
8. how is serine synthesis regulated?
9. how is glycine synthesized?
10. how does glycine relate to kidney stones?
cysteine...
11. describe the synthesis of cysteine.
12. describe the regulation of the synthesis of cysteine.
13. how is methionine involved in cysteine synthesis?
14. describe the degradation of cysteine.
15. how is alanine synthesized?
amino acids related to TCA cycle intermediates...
16. which TCA cycle intermediates can be used to synthesize amino acids?
17. which TCA intermediates can be replenished by anaplerotic reactions via amino acids?
18. explain the statement "glutamate can be both derived from glucose and converted to glucose".
19. what are the three enzymes in the body that can "fix" free ammonia?
20. why is glutaminase important in the kidney?
alpha keto glutarate derived amino acids...
21. describe the synthesis of proline.
22. how is arginine synthesized?
23. what is the enzyme that transaminates glutamate 5-semialdehyde into ornithine?
24. describe the synthesis of aspartate and asparagine.
amino acids that supply succinyl CoA...
25. which amino acids degrade to form succinyl CoA?
26. describe the degradation of methionine to succinyl CoA.
27. describe the degradation of threonine to succinyl CoA.
28. where does most branched chain amino acid oxidation occur?
29. how are the degradations of valine and isoleucine both anaplerotic and energy producing?
30. what does degradation of leucine form?
ketogenic amino acids...
31. what are the main ketogenic amino acids?
32. describe how phenylalanine can produce ketone bodies.
33. what does tryptophan degradation produce?
34. what does degradation of lysine form?
answers
1. pyridoxal phosphate (PLP) (see chapter 38), FH4, and BH4.
2. the N on the amino acids bind to the aldehyde carbon of the PLP and pulls electrons away from the alpha carbon on the amino acid, allowing for different reactions to occur.
3. FH4 is required to donate or accept one carbon groups. it is derived from the vitamin folate.
4. BH4 is important for ring hydroxylation reactions.
5. serine, glycine, cysteine, and alanine.
6. 3-phosphoglycerate is oxidized to 3-phosphohydroxypyruvate, by 3-pg dehydrogenase. 3-phosphohydroxypyruvate is then transaminated to phosphoserine. the phosphate from phosphoserine is then removed to form serine.
7. serine is transaminated to hydroxypyruvate. hydroxypyruvate is reduced and phosphorylated to form 2-phosphoglycerate, which then forms PEP and pyruvate.
8. when serine levels fall, higher levels of 3-phosphoglycerate dehydrogenase are induced, and inhibition of phosphoserine phosphatase by serine is relaxed.
9. the major pathway of glycine synthesis is a conversion of serine, involving FH4 and PLP. the minor pathway is through the degradation of threonine in an aldolase-like reaction.
10. glycine can be converted to glyoxalate, which can be oxidized to oxalate- the accumulation of which can cause kidney stones.
11. homocysteine combines with serine to form cystathione. cystathione is cleaved to form propionyl CoA (which is converted to succinyl CoA) and cysteine.
12. cysteine inhibits the cystathione synthase; thereby inhibiting its own production.
13. methionine, an essential amino acid, provides the sulfur for cysteine synthesis. if methionine is in short supply, cysteine can not be synthesized de novo and becomes an essential amino acid.
14. degradation of cysteine produces pyruvate, NH4, and sulfate.
15. alanine is synthesized from the transamination of pyruvate via alanine aminotransferase (ALT).
16. oxaloacetate, alpha-keto glutarate.
17. oxaloacetate, alpha-keto glutarate, succinyl CoA, fumarate.
18. glutamate is derived from alpha-ketoglutarate, which is derived from glucose via the TCA cycle. in the liver, it can be degraded back into alpha-ketoglutarate, which leads to the formation of malate, which produces glucose via gluconeogenesis.
19. carbamoyl phosphate synthetase I (first reaction from the urea cycle), glutamate dehydrogenase, and glutamine synthetase.
20. glutaminase catalyzes the release of NH3 from glutamine, which then is secreted into the renal tubules and is the basis of the ammonia buffer system which aids in the excretion of H+.
21. glutamate is reduced to glutamate 5-semialdehyde, which then spontaneously forms a cyclical structure. this is then reduced to proline.
22. glutamate 5-semialdehyde can be converted to ornithine via a transamination reaction. ornithine can then be used to fuel the urea cycle, which produces arginine.
23. ornithine aminotransferase.
24. aspartate is transaminated from oxaloacetate (see chapter 38 notes). aspartate can be converted to asparagine by aspargine synthetase.
25. methionine, valine, isoleucine, threonine.
26. see question 13. methionine is converted to S-adenhosylhomocysteine, which is converted to homocysteine, which combines with serine to form cystathione. cystathione cleaves to produce cysteine and alpha-keto butyrate, which can be converted to propionyl CoA and ultimately succinyl CoA.
27. threonine is converted to alpha-keto butyrate by a hydratase, using PLP as a cofactor. alpha-keto butyrate is converted to succinyl CoA in the same path as for methionine degradation to succinyl CoA.
28. in muscle.
29. in both degradation pathways, they are transaminated to the alpha keto acids, then oxidatively decarboxylated to acyl CoA's. at this point they are oxidized just like fatty acyl CoA's using beta oxidation, producing NADH, FADH2, and propionyl CoA, which can be converted to succinyl CoA. thus the NADH and FADH2 provides energy while the succinyl CoA replenishes the TCA cycle.
30. leucine, the third branched chain amino acid, does not form succinyl CoA- instead it just produces acetoacetate and acetyl CoA (and thus is "ketogenic")
31. phenylalanine, tyrosine, isoleucine, threonine, tryptophan.
32. phenylalanine is converted to tyrosine, which is ultimately converted into acetoacetate (a ketone body) and fumarate.
33. alanine, formate, and acetyl CoA.
34. acetyl CoA, and NADH, FADH2.
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