Amino Acid Metabolism part 2 Flashcards
What are glucogenic AA
Amino acids whose catabolism yields pyruvate or one of the inter- mediates of the citric acid cycle are termed glucogenic.
What are ketogenic AA. Which ones?
Amino acids whose catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA) are termed ketogenic
Leucine
Lycine
What are the products of AA catabolism?
FOSKAAP Fumarate Oxaloacetate Succinate Alpha ketoglutarate Acetyl coa Acetocacetyl coa pyruvate
Which AA are both ketogenic AND glucogenic?
Tyrosine (nonessential)
Isoleucine
Phenylalanine
Tryptophan
How is asparagine metabolized?
asparagine (aspariginase + H2O) -> aspartate release of ammonia
aspartate (AST) rxn
aspartate +alphaketoglutarate -> oxaloacetate formed and glutamate accepts amine group
the free ammonia can be transported to liver via glutamine or alanine
Where do you see aspariginase deficiency?
some leukemia cells cannot synthesize asparaginase. Tx: asparaginase can be administered systemically.
If you lower circulating levels of asparagine, leukemia cells will not proliferate (required nutrient).
How is histidine degraded?
histidine oxidative deamination by histidase -> urocanic acid –> FlGlu
FlGlu -> glutamate via THF (tetrahydrofolate)
glutamate -> alphaketoglutarate
How is phenylalanine degraded?
Hydroxylation of phenylalanine by phenylalanine hydroxylase produces tyrosine
requires tetrahydrobiopterin and O2 -> DH2 and H2O
(DH2 recycled through other mechanism)
Tyrosine-> fumarate and acetoacetate
What is PKU
Phenylketonuria
deficiency of phenylalanine hydroxylase
tx: screen at birth; limit phenylalanine in diet, however it is an essential amino acid- titrate amount necessary for development that will cause the least amount of harm to pt
How is methionine degraded?
Methionine condenses with ATP-> SAM—a high-energy compound that is unusual in that it contains no phosphate. Has a thioether bond. This rxn driven by hydrolysis of all three phosphate bonds in ATP
SAM (methyltransferase +methyl acceptors)-> SAH (and methylated product)
SAH (SAH hydroxylase+ H2O) ->
L-homocysteine (adenosine leave)
L-homocyteine can be converted to cysteine using B6 in a transulfuration rxn or back to methionine via folate and vit B12 (methylocobalamin) in a remethylation process.
What are the branched chain AAs and how are they degraded?
leucine, valine and isoleucine
they undergro transamination to their corresponding alpha ketoacid
THEN, oxidative decarboxylation to corresponsing CoA via alphaketoacid dehydrogenase
FINALLY, FAD-linked dehydrogenation requiring biotin and B12 derivative
Final products: Acetoacetate, Acetyl CoA and Succinyl CoA
What do the aminotransferase reactions of alanine, aspartate, and glutamate result in?
alanine-pyruvate
aspartate-oxaloacetate
glutamate-alpha-ketoglutarate
from last lecture
What is tyrosine a precursor of?
THREE catecholamines
dopamine, norepinephrine, epinephrine
First: rate limiting reaction
tyrosine (tyrosine hydroxylase +BH4) -> DOPA (and BH2)
BH4- tetrahydrobiopterin
BH2- dihydrobiopterin
Second:
DOPA (Aromatic AA decarboxylase +PLP) -> Dopamine (CO2 leaves)
Third:
Dopamine (Dopamine-beta-hydroxylase + ascorbic acid + copper) -> NE (dehydroascorbate and H2O leaves)
Fourth:
NE (Phenylethanolamine-N-methyl transferase + SAM) -> Epinephrine (SAH)
What does cocaine do?
inhibits dopamine and NE reuptake in brain
What is parkinson’s disease? How is it treated?
neurodegenerative movement disorder affecting 1 million people in US
Symptoms: cognitive impairment, spontaneous movement, resting tremor, shuffling gait, muscle rigidity, depression, mask-like facial expression, severe constipation
Results from degeneration of dopamine neurons in substantia nigra pars compacta
this has projections to the striatum, which is involved in voluntary muscle control
ALSO Arcuate nucleus of hypothalamus- releases dopamine- regulation of secretion of prolactin from AP
Tx: oral administration of L-DOPA (dopamine precursor), results diminish after 5 years
10% due to inherited mutations
