Amino Acid Metabolism - RR Flashcards
What are the symptoms of ammonia toxicity?
Irritability, vomiting, lethargy, confusion, respiratory distress, migraines
Ammonia toxicity results in neurological symptoms. What is the proposed mechanism involving neurotransmitters that explains this?
- Brain glutamate dehydrogenase converts alpha-ketoglutarate to glutamate. This decreases the amount of alpha-ketoglutarate and TCA.
- Glutamine synthase converts glutamate to glutamine (which can store more ammonia). But need glutamate to make GABA. So lose GABA production
- Glutamine leaves the brain in exchange for tryptophan. Tryptophan is then converted to serotonin which can lead to coma.
When ketogenic amino acids are degraded, what is formed?
Acetyl CoA or acetoacetyl CoA which then gives rise to ketones
When glucogenic amino acids are degrades, what is formed?
Pyruvate or CAC intermediates which can give rise to glucose
What two amino acids are considered ketogenic?
leucine and lysine
What amino acids can be degraded to eventually produce pyruvate? (there are 6)
Threonine, Gylcine, Tryptophan, Alanine, Serine, Cysteine
What amino acids can be degraded to eventually produce alpha-ketoglutarate? (there are 5)
arginine, histidine, glutamine, proline, glutamate
Which amino acids can be degraded to eventually produce succinyl CoA? (there are 4)
valine, threonine, isoleucine, methionine
Which amino acids can be degraded to eventually produce fumarate? (there are 3)
aspartate, tyrosine, phenylalanine
Which amino acids can be degraded to form oxaloacetate? (there are 2)
arginine, asparagine
What amino acid can pyruvate form? What is this reaction? What enzyme performs this reaction?
Alanine; alanine transaminase (ALT)
Pyruvate + glutamate –> alanine + alpha-ketoglutarate
What enzyme performs serine degradation? What is the product?
Serine dehydratase
Pyruvate
There are three pathways for glycine degradation. What are they?
- Glycine to serine which then goes onto pyruvate (serine hydroxymethyl transferase does this reaction)
- Glycine to CO2 and NH4+ and 5,10-methylene THF (this is important because of the THF as a cofactor)
- Glycine to CO2 and NH4” by glycine cleavage enzyme
Amino acids with 4 carbons typically are converted to what CAC intermediate?
oxaloacetate
Amino acids with 3 carbons are typically converted to what glycolytic intermediate?
pyruvate
Amino acids with 5 carbons are typically converted to what CAC intermediate?
alpha-ketoglutarate (via glutamate formation)
What two reactions use THF (tetrahydrofolate)?
Glycine to serine
Histidine to glutamate
What are ALT and AST?
“liver enzymes”
Alanine aminotransferase and aspartate aminotransferase
What is the pathway for arginine degradation?
Arginine is a product of the urea cycle. Arginase (irreversible enzyme) cleaves arginine into urea and ornithine. Ornithine is then converted to glutamate via THF and ultimately to alpha-ketoglutarate
Branched amino acids are typically converted to what CAC intermediate?
succinyl-CoA
What are the general steps in the conversion of branched amino acids into their CAC intermediate?
- Branched chain transaminase converts into the AA specific keto-acid
- The AA specific keto-acid is then converted to get the AA derivative bound to CoA - by branched-chain keto acid dehydrogenase (same mechanism as pyruvate dehydrogenase)
A defect in what enzyme causes maple syrup disease? How is it treated?
Branched chain keto-acid dehydrogenase
Treatment: Dietary restriction to avoid the amino acid, in some cases high doses of thiamine
How is tyrosine normally formed? What enzyme and what cofactor?
Hydroxylation of phenylalanine via phenylalanine hydroxylase with cofactor tetrahydrobiopterin
A defect in which enzyme causes PKU? What builds up? How is it treated?
Defect in phenylalanine hydroxylase so phenyalanine builds up and get toxic derivatives of phenylalanine like phenylpyruvate
Treatment: diet- avoid foods with phenylalanine
