amino acids as metabolic precursors

Question 1

phenylalanine hydroxylase

Answer 1

converts phenylalanine to tyrosine

requires coenzyme tetrahydrobiopterin

Question 2

phenylpyruvate

Answer 2

made from phenylalanine when the enzyme phenylalanine hydroxylase isn’t present to convert the phenylalanine to tyrosine
used to make phenyllactate and phenylacetate

Question 3

phenylketonuria (PKU)

Answer 3

for of hyperpheylalmineima
high blood levels of phenylalanine (20 fold increase) because of lack of phenylalanine hydroxylase (in 75% of cases) but over 40 known mutations have been found to cause it
results in phenylalanine being converted to phenylpyruvate rather than to tyrosine and high levels of phenyllactate and phenylacetate (made from phenylpyruvate)
detected by testing for elevated phenylalanine blood levels in newborns
treated by low phenylalnine diet (no aspartame) and high phenylalanine and tyrosine - need the low phenylalanine because buildup inhibits tyrosine hydroxylase
results in developmental defects, hyperactivity, mental retardation
pigmentation deficiencies because melanin made from tyrosine and no tyrosine is made
aka ketonuria
severity of symptoms correlates with level of hydroxylase function and serum phenylalanine concentration

Question 4

tyrosine derivatives

Answer 4

made from phenylalanine by phenylalanine hydroxylase

used to make tissue proteins, melanin, catecholamines, fumarate

Question 5

hyperphenylalaninmias

Answer 5

PKU is one

can also be caused by deficiencies in enzymes that synthesize or reduce biopterin

Question 6

biopterin

Answer 6

coenzyme for phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase
therefore important for synthesis of NT s.a. catecholamines and 5HT
active form is fully reduced tetrahydrobiopterin
synthesized by GTP cyclohydrolase and dihydrobiobterin synthasized from vitamin B12
reduced by dihydropteridine reductase
de novo synthesis can occur from GTP by enzymes GTP cyclohydrolase and dihydrofolate reductase
folic acid deficiency results in large megaloblasts

Question 7

dihydrofolate reductase

Answer 7

converts dihydrobiopterin to tetrahydrobiopterin (active form)
uses NADPH - gives off NADP+
problems with this enzyme can cause PKU, but the symptoms will be more severe from this mutation because will also get problems in DOPA and 5HT synthesis

Question 8

dihydropteridine reductase

Answer 8

enzyme that converts quinoid dihydrobiopterin to tetrahydrobiopterin (active form)
uses NADPH - releases NADP+

Question 9

synthesis of catecholamines

Answer 9

1: tyrosine hydroxylase converts tyrosine to DOPA using O2 and tetrahydrobiopterin - releases H20
2: DOPA-decarboxylase converts DOPA to dopamine - releases CO2 - needs vitamin B6 (pyrodoxal-P)
3: dopamine beta-hydroxylase converts dopamine to norepi - uses ascorbate and O2 as cofactors - releases dehydroascorbate and H2O
4: dopamine or norepi made from DOPA

mutation in GTP cyclohydrolase, dihydrobiopterin sythetase or dihydropteridine reductase block synthesis of DOPA (in addition to causing hyperphenylalaninemia)

Question 10

serotonin (5HT) synthesis steps

Answer 10

1: tryptophan hydroxylase converts tryptophan into 5-hydroxy tryptophan using O2 and tetrahydrobiopterin - releases H2O and dihydrobiopterin
2: decarboxylase enzyme decarboxylates the 5-hydrotryptophan to make serotonin - releases CO2 and requires vit B6 (pyridoxal P) as cofactor
5HT converted to serotonin

mutations in GTP cyclohydrolase, dihydrobiopterin synthetase or dihydropteridine reductase can all cause reduction in synthesis of 5HT (as well as hyperphenylalaninemia)

Question 11

DOPA

Answer 11

made by tyrosine hydroxylase from tyrosine
tetrahydrobiopterin and O2 needed to synthesis
precursor to melanin synthesis and dopamine and norepinephrine synthesis
hyperphenylalanemias result in pigmentation deficits because of lack of DOPA

Question 12

serotonin (5-HT) synthesis

Answer 12

involved in smooth muscle contraction, pain perception, and behavior
psycotropic agents can affect action
made from tryptophan by tryptophan hydroxylase and decarboxylase

Question 13

histamine synthesis

Answer 13

histidine decarboxylated to histimine - release CO2
chemical messenger that mediates allergic and inflammatory reactions and gastric acid secretion
binds to receptor that triggers release of HCl in stomach

Question 14

GABA synthesis

Answer 14

glutamate decarboxylated

one of brain’s major inhibitory NT

Question 15

nitric oxide synthesis

Answer 15

made by NO synthase from L-arginine
O2 needed
creates L-citrulline
uses NADPH, H+ and releases NADP+
free radical so only stable for short period of time and has local effects
acts as NT, in immune function, and smooth muscle relaxation

Question 16

tyrosine hydroxylase

Answer 16

enzyme in first step of synthesis of catecholamines from tyrosine
converts tyrosine to DOPA
uses tetrahydrobiopeterin and O2 as cofactors
inhibited by elevated phenylalanine levels because phenylalanine is a competitive inhibitor

Question 17

ketonuria

Answer 17

problems in converting phenylalanine to tyrosine result in ketonuria too - buildup of phenylalanine results in increased formation of phenyl pyruvate, which is a ketone

Question 18

DOPA decarboxylase

Answer 18

enzyme in second step of synthesis of catecholamines from tyrosine
converts DOPA to dopamine
releases CO2
needs vit B6 (pyrodoxal-P) as cofactor

Question 19

dopamine hydroxylase

Answer 19

enzyme in third step of synthesis of catecholamines from tyrosine
makes norepi from dopamine
uses ascorbate and O2 as cofactors
releases dehydroascorbate and H2O

Question 20

pyridoxal P

Answer 20

derived from vit. B6
cofactor for many enzymes including decarboxylase in serotonin synthesis and in dopa synthesis
binds at the active site for aminotransferases, but in these processes it generates CO2 instead of an amino group transfer

Question 21

ways mutations that can cause PKU can occur

Answer 21

1: point mutations in open reading frame produce mutant protein
2: promotor mutations influence mRNA expression levels
3: splicing mutations produce inactive mRNA transcript

Question 22

treatments for BH4 deficiencies

Answer 22

must start early
diet low in phenylalanine and suppemented with tyrosine - synthetic diet, many restrictions
replacement therapy with biopterin, DOPA and T-HT
limited success, probably because not all cells/tissues have transporters for these compounds

Question 23

treatment for PKU

Answer 23

must start early, must be detected early
diet low in phenylalanine, supplemented with tyrosine
synthetic diet, many restrictions
genetic disorder, but environmental disease
foods/beverages often contain warning labels