One-Carbon Metabolism - RM Flashcards
What is the precursor of dopamine?
tyrosine
What is the precursor of epinephrine (E)?
tyrosine
What is the precursor of melanin?
tyrosine
What is the precursor of norepinephrine (NE)?
tyrosine
What is the precursor of thyroxine?
tyrosine
What is the precursor of GABA?
glutamate
What is the precursor of histamine?
histidine
What is the precursor of serotonin?
tryptophan
What is the precursor of melatonin?
tryptophan
What is the precursor of niacin?
tryptophan
What is the rate limiting step of catecholamine biosynthesis? What is it inhibited by?
tyrosine hydroxylation to dopa (1st step), allosteric inhibition by dopamine, NE, epinephrine (E)
How is dopamine formed from tyrosine?
tyrosine hydroxylated to dopa (tyrosine hydroxylase with tetrahydrobiopterin cofactor)
dopa decarboxylated to dopamine (aromatic acid decarboxylase with pyroxidal phosphate cofactor)
Why can’t people with atypical PKU make catechols?
they can’t regenerate tetrahydrobiopterin from dihydrobiopterin so can’t hydroxylate tyrosine (1st step in catecholamine biosynthesis)
What happens in reactions with pyridoxal phosphate (PLP) cofactor?
decarboxylation is always adjacent to amino group
How is NE formed from dopamine?
dopamine is hydroxylated (dopamine beta hydroxylase with Cu, ascorbate, and molecular oxygen cofactors)
How is E formed from NE?
NE methylated (phenylethanolamine N-methyltransferase with SAM cofactor)
How are catecholamines degraded?
monoamine oxidase
Where is melanin produced? What is a defect in melanin production called?
synthesized in melanocytes, albinism
What can a deficiency in tryptophan cause?
pellagra (niacin deficiency)
How is GABA synthesized?
glutamate is decarboxylated (glutamate decarboxylase with pyridoxal phosphate cofactor)
How is histamine synthesized?
histidine is decarboxylated (histidine decarboxylase with pyridoxal phosphate cofactor)
What 4 things does the body need 1 C fragments for?
- formation of methionine from homocysteine
- biosynthesis of purines
- biosynthesis of pyrimidines
- biosynthesis of glycine from CO2 and NH4+ by glycine synthase
What kind of 1 C fragment does biotin carry?
CO2 groups (most oxidized)
What carries 1 C groups of all oxidation states except CO2?
tetrahydrofolic acid (THF)
What does conjugase do? Where is it located?
cleaves the gamma-peptidyl linked glutamates off of folate (from diet) to leave just one glutamate moiety to make it easier to absorb, in the intestinal mucosal cells
What type of cells use a lot of folate? Why do they use a lot of folate?
rapidly dividing cells, need folate to make nucleotides for DNA synthesis
What is the site of action of chemotherapeutic drugs?
dihydrofolic acid reductase
What is the most reduced form of THF?
N5-methyl-tetrahydrofolic acid
What is the only reaction that consumes N5 methyl THF?
formation of methionine from homocysteine
What is the main source of N5N10-methylene THF?
conversion of serine to glycine to CO2 and NH4+
What is the serine to glycine reaction a direct connection between?
glycolysis (G3P–> serine) to 1 Carbon pool (N5N10-methylene-THF)
What is one of the first symptoms of folate deficiency?
anemia
What are 3 drugs that can cause folate deficiency?
oral contraceptive, barbituates from impaired absorption, methotrexate inhibits dihydrofolate reductase
What does folate deficiency in pregnancy cause?
neural tube defects (spina bifida)
What is S-adenosylmethionine (SAM)? What are 5 examples of reactions it acts as a cofactor for?
carrier of methyl groups
- NE to epinephrine
- guanidinoacetate to creatine
- acetylserotonin to melatonin
- phosphatidylethanolamine to phosphatidylcholine
- methylation of DNA
What happens in the activated methyl cycle? (2 steps)
- adenosyl of ATP transferred to sulfur of methionine converting it to SAM
- Methyl attached to S of SAM transferred to acceptor to give methylated product and SA-homocysteine
What enzyme regenerates methionine from homocysteine? What are the cofactors?
homocysteine methyltransferase, N5-methyl THF and vitamin B12
What are elevated levels of homocysteine associated with? What 3 things reduce homocysteine levels?
increased risk for atherosclerosis, vitamin B12, folate (THF) and pyroxidal phosphate reduce homocysteine by helping to activate enzymes that reduce it
What can homocysteine be metabolized to besides methionine?
cysteine (via cystathione)
What is homocystinuria?
- deficiency in cystathione beta-synthetase enzyme or pyroxidal phosphate cofactor that catalyzes homocysteine to cystathione conversion
- deficiency in homocysteine methyltransferase, THF, or vit. B12 can cause it too
Why can pyroxidal phosphate (PLP) be used to treat homocystinuria?
some forms are due to inadequate binding of PLP cofactor to enzyme, by adding more PLP it reduces the deficiency
What does gamma-cystathionase do? What does a deficiency in it cause?
hydrolyzes cystathione to cysteine and alpha-ketobutyrate, cystathionuria
Pernicious (megaloblastic) anemia is associated with a deficiency in…
vitamin B12 or intrinsic factor
Why are elderly people typically vitamin B12 deficient?
secrete less intrinsic factor which is necessary to bind and absorb vit. B12
How are forms of cobalamin (vit B12) classified?
by the group attached to the 5th bone above the plane of the ring
What two reactions involve vitamin B12?
- conversion of Lmethylmalonyl CoA to succinyl coA
2. conversion of homocysteine to methionine
How do you supplement vitamin B12 in a patient with low intrinsic factor?
injections of vitamin B12 so already in bloodstream and doesn’t need to be absorbed into it using intrinsic factor
What is transcobalamine?
transporter protein for vit. B12 in body
What is the folate trap?
when vit. B12 is deficient, folate is trapped in N5-methyl THF form
N5 methyl THF only used in homocysteine to methionine and if you don’t have vitamin B12 homocysteine methyl transferase can’t run that reaction
What is the danger associated with folate supplements in grains?
if you have vit. B12 deficiency, folate builds up as N5 methyl THF
if you supplement with folate, you will keep accumulating more N5 methyl THF as you use the folate supplement so won’t be anemic but will have irreversible neurological damage from N5 methyl THF
