L27-28: Protein and AA Metabolism III-IV Flashcards
How are amino acids used in the fasting and well-fed states?
- Fasting state: used to supply energy via breakdown of proteins funneled into TCA cycle - Well-fed state: converted into glucose or FAs for storage of glycogen and triacylglycerols respectively
What happens to ammonia released during amino acid catabolism?
- Urea cycle, excreted
What is meant by glucogenic AAs? Which are these? What is meant by ketogenic AAs? Which are these? Which are both?
- Glucogenic = These AAs can be converted into glucose via TCA intermediates (alpha-kg, succ coa, fumarate, OAA) and pyruvate – anything that generates OAA, an intermediate in gluconeogenesis - Ketogenic = These AAs can be converted into acetyl-CoA and acetoacetyl-CoA, can never become glucose - Gluco/ketogenic AAs = TIPhe mnemomic = all T AAs (thr, tyr, trp), iso, phe - Ketogenic AAs = all L AAs - Glucogenic AAs = all others
Glucogenic AAs?
- All AAs except for TIPhe and L AAs
Ketogenic AAs?
- TIPhe = try, trp, tyr, iso and phe
Gluco-/ketogenic AAs?
- L starting AAs – leucine, lysine
Major source of amino acids during fasting?
- Striated muscle protein
What enzyme is involved in regulating AA catabolism? How does regulation occur?
- Primarily regulated by liver glutamate dehydrogenase (in mitochondria) - Regulation of glutamate DH is by cellular energy charge - High energy (high GTP, high NADH) = inhibition of enzyme - Low energy (high ADP) = activation of enzyme
Regulation of GDH
- High energy (high GTP, high NADH) = inhibition of enzyme = decreased formation of alpha-KG - Low energy (high ADP) = activation of enzyme = increased formation of alpha-KG
Describe familial hyperinsulinemic hypoglycemia type 6. Causes? Result?
- Mutations to glutamate dehydrogenase enzyme rendering it insensitive to inhibition by GTP. - As a result, increased AA catabolism occurs in environment that is high energy - Leads to elevated levels of ATP and hyperammonemia - Increased ATP in beta-cell promotes insulin releases, resulting in hypoglycemia - Less active urea cycle with more ammonia production = hyperammonemia
Which AAs are converted into pyruvate?
- Mnemonic: Some Good Children are Pyrates - Serine, Glycine, Cysteine, Alanine = Pyruvate
Describe the synthesis of pyruvate from AAs.
Describe glycine cleavage system
- Mechanism to degrade glycine and produce N5 N10 methylene THF or reverse to glycine
Which AAs can be used to synthesize Oxaloacetate?
- Every AAs used to generate pyruvate, then pyruvate into OAA via pyruvate carboxylase - In addition, aspartate and asparagine – Ox with a big ASP (ass)
Describe synthesis of OAA from AAs
Which AAs can be used to synthesize alpha-ketoglutarate?
- Mnemonic: Greg’s Hot Girlfriends Are Pregnant Ovals - Glutamine, Histidine, Glutamate, Arginine and Proline (and ornithine)
Describe synthesis of alpha-ketoglutarate from AAs
Which AAs can be used to synthesize succinyl-CoA? How?
- Mnemonic: VOMIT - Valine, odd-chain fatty acids, methionine, isoleucine, threonine - These are converted into propionyl-CoA, which undergoes intermediates to become succinyl-CoA
Describe synthesis of succinyl-CoA from AAs.
What are inborn errors of metabolism relating to synthesis of succinyl-CoA from AAs?
- AAs = VOMIT (valine, odd chain FAs, methionine, isoleucine, threonine) - 1.) deficiency in propionyl-CoA carboxylase resulting in propionic / propionyl acidemia - 2.) deficiency in racemase resulting in D-methylmalonyl aciduria - 3.) deficiency in mutase (or Vit B12, required as cofactor) resulting in methylmalonyl aciduria
What disorders is vitamin B12 deficiency linked to?
- Anemia
Source of vitamin B12.
- Meats and shellfish, with ultimate source as bacteria. No vitamin B12 in plants
Is vitamin B12 found in plants?
- Absolutely not, never, heck no!
Describe vitamin B12 absorption into body and storage
- R-binders in salivary enzymes bind B12 and pass it onto intrinsic factor, produced by stomach parietal cells - Absorbed in ileum through receptor mediated endocytosis - Binds to transcobalamin and is transported to tissues - Preferentially distributed to liver as vit-B12:transcobalamin complex and stored there. Kidney has some B12 stores