Amino acids as precursors

Question 1

Phenylalanine metabolism

Answer 1

Hydroxylase:
Phen + tetrahydro-biopterin -> Tyr + quinoid dihydro-biop
Tyrosine used for melanin, catecholamines, fumarate, acetoacetate
Requires biopterin

Minor:
Phen + a-Keto acid -> phenylpyruvate (ketone) + a-amino acid
(phenylpyruvate -> ph-acetate, ph-lactate)

Question 2

Biopterin

Answer 2

GTP -> GTP cyclohydrolase -> DHB synthase ->
dihydrobiopterin (DHB) -> DHB reductase ->
THB = reduced/active form

THB oxidized to DHB in multiple reactions

• Phen -hydroxylase> Tyr
• Tyr -hydroxylase> DOPA
• Tryp -hydroxylase> 5HT

Recycled/reduced by DHB reductase

Question 3

Phenylketonuria

Answer 3

• elevated conc of Phe in tissues, plasma, and urine
• caused by defects in Phe hydroxylase
• Phe inhibits tyrosine hydroxylase, other cell fx
• lack of production -> Tyr deficient
• disrupts CNS dev’t -> retarded, hyperactive, etc
• diagnose early and manage diet (no Phe, high Tyr)

Question 4

Overview of neurotransmitter pathways

Answer 4

Phen -> Tyr -> epi, norepi, DOPA, melanin
Tryp -> 5HT -> serotonin
Hist -> histamine
glutamate -> GABA
Arg -> polyamines, NO

Question 5

Hyperphenylalaninemia

Answer 5

• elevated conc of Phe in tissues, plasma, and urine
• caused by defects in mb of aromatic amino acids (Phe, Tyr, and Try)
• PKU is specific type
• more severe = BH4 (THB)
• GTP cyclohydrolase, DHB synthetase, DHB reductase
• block synthesis of DOPA (-> catecholamines) and 5-HT (-> serotonin)
• tx with low Phen, high Tyr, replace biopterin, DOPA, 5HT

Question 6

Catecholamine synthesis

Answer 6

(Phen -hydroxylase> Tyr)
Tyr + BH4 -hydroxylase> DOPA + DHB

DOPA

• > melanin
• decarboxylase> dopamine (requires B6/PLP)
• > dopamine -> NE

Tyrosine hydroxylase is inhibited by Phen (untreated PKU)

Question 7

Serotonin synthesis

Answer 7

Tryp + THB -hydroxylase> 5HT + DHB

5HT -decarboxylase> serotonin (requires B6/PLP)

Question 8

Histamine synthesis

Answer 8

Histidine -decarboxylase> Histamine

Requires B6/PLP

Question 9

GABA synthesis

Answer 9

Glutamate -decarboxylase> GABA

Requires B6/PLP

Question 10

Nitric oxide synthesis

Answer 10

Arg + NADPH + O2 -NO synthase> Citrulline + NADP + NO