Amino Acid Metabolism Biomchem –
Amino acids can be used for energy Alanine is a major source for gluconeogenesis –
Amino acids:
• Leucine and valine are branched
• Nonpolar side chains form hydrophobic interactions
• Uncharged polar side chains are water soluble
• Folding of amino acids gives the lowest energy state and it gives functionality
Non-Essential amino acids:
• Alanine and serine
• Asparagine and aspartic acid
• Cysteine
• Glutamic acid and glutamine
• Glycine and proline
• Tyrosine
Essential amino acids:
• Arginine (children)
• Histidine
• Isoleucine and leucine
• Lysine and methionine
• Phenylalanine and threonine
• Tryptophan and valine
Ketogenic amino acids: Leucine and lysine
Ketogenic and glucogenic amino acids: Phenylalanine, tyrosine, tryptophanm isoleucine, an
threonine
Glucogenic amino acids: All other amino acids
Glutamine synthase Adds a nitrogen to glutamate to make glutamine –
Glutaminase Glutamine to glutamate. Buffers excess H+. Acidosis will induce glutaminase to –
produce ammonia (H + NH3 = NH4). NH4 stays in the blood stream.
Aminotransferase (transaminase) unlike deaminase, does not release free NH4. Transfer –
amino groups between amino acids.
Glutamate dehydrogenase Glutamate to alpha-ketoglutarate. –
Urea cycle:
• Begins in the mitochondria and finishes in the cytosol.
• Starts with ammonia or aspartate.
• NH4 and CO2 make carbamoyl phosphate by carbamoyl phosphate synthase I.
• Ornithine and carbamoyl phosphate make citrulline by ornithine transcarbamoylase.
• Citrulline leaves the mitochondria and is converted to arginosuccinate by
arginosuccinate synthetase and aspartate.
• Arginosuccinate is converted to arginine by arginosuccinate lyase.
• Arginine is converted to urea by arginase and ornithine is left over to help convert
carbamoyl phosphate into citrulline in the mitochondria.
• Allosteric regulator of CPSI is N-acetyl glutamine.
Ornithine can also be formed to make glutamate by ornithine aminotransferase.
Where is CPSI? Mitochondria
Where is CPSII? Cytosol
What is CPSI involved in? Urea cycle
What is CPSII involved in? Pyrimidine synthesis
Why is there increased blood glutamine in carbamoyl phosphate synthetase deficiency?
Glutamine helps pick up excess nitrogen. If there is carbamoyl phosphate synthetase deficiency,
ammonia is not able to be converted to carbamoyl phosphate, so there is an increased amount
of ammonia. The patient has hyperammonemia but is trying to compensate with elevated
blood glutamine to pick up the excess nitrogen.
Why does ornithine transcarbamoylase deficiency present with hyperammonemia and
increased blood glutamine? The same reason carbamoyl phosphate synthetase deficiency does.
Carbamoyl phosphate can’t get converted to citrulline without OTC so there is a backup of
carbamoyl phosphate, leading to a backup of ammonia. The patient has hyperammonemia but
is trying to compensate with elevated blood glutamine to pick up the excess nitrogen.
CPSI can be impaired if you have a lot of propionic acid, NAG will not form. NAG is an allosteric
activator of CPSI and is formed from acetyl CoA and glutamate. With elevated propionic acid,
propionic acid will take the place of acetyl CoA and NAG will not form.
What is the only defect in the urea synthesis pathway that does not present with
hyperammonemia? Arginase I deficiency.
How many nitrogen does Na Benzoate pick up? 1
How many nitrogen does Phenylacetate pick up? 2
Phenylalanine metabolism:
• Under normal circumstances, phenylalanine is converted to tyrosine. If phenylalanine
can’t be converted to tyrosine, it is converted to phenylpyruvate, leading to
phenyllactate and phenylacetate.
• Tyrosine leads to melanin production, tissue protein production, catecholamine
production, and fumarate acetoacetate production.
What can cause hyperphenylalaninemia in the phenylalanine metabolism?
Deficient phenylalanine hydroxylase or BH4. All pathways use BH4 (tyrosine, catecholamines,
and serotonin) but only tyrosine uses phenylalanine hydroxylase.
What is the pathway for tyrosine metabolism?
Tyrosine DOPA Dopamine Norepinephrine Epinephrine → → → →
What is in the urine if epinephrine or norepinephrine is broken down? Vanillylmandelic acid
(VMA).
What is in the urine if dopamine is broken down? Homovanillic acid (HVA)
What is the most common cause of phenylketonuria? Impaired Phenylalanine hydroxylase
(PAH) function.
What do patients present with that have phenylketonuria? Skin problems, light sensitivity, and
hair loss from decreased melanin. Also decreased intellectual disability from decreased
neurotransmitters.
What is tetrahydropteridine (BH4)? A co-factor for PAH, tyrosine hydroxylase, tryptophan
hydroxylase, nitric oxide synthase, and glyceryl-ether mono-oxygenase. It is synthesized from
GTP.
What do drugs that inhibits folate synthesis also inhibit? BH4 synthesis.
What are the 2 types of melanin tyrosine is converted into? Pheomelanin and eumelanin.
What is melanin synthesized in? Melanosomes of melanocytes.
What causes maple syrup urine? Branched-chain ketoacid dehydrogenase deficiency. Branched-
chain ketoacid dehydrogenase metabolizes valine, leucine, and isoleucine to acetyl coa, goes to
TCA cycle. Since the patient can’t metabolism these amino acids, it’s treated with a dietary
restriction of these three amino acids. Patient should also avoid fasting.
