One Carbon Metabolism Flashcards
biotin
transfers CO2 groups
S-adenosylmethione (SAM)
transfers methyl groups
tetrahydrofolate (THF)
transfers carbon in a variety of oxidation states
biotin is a cofactor for _
pyruvate carboxylase in the formation of OAA from pyruvate
biotin deficiency
leads to defects in fatty acid synthesis, TCA cycle, ketone formation; symptoms include fatigue, depression, nausea, anemia, hair loss, heart disorders, movement disorders, and paresthesia (burning in hands)
biotin deficiency can be due to _
diet, defect in biotinidase, or defect in holocarboxylase synthetase
biotinidase
recycles biotin and releases biotin from proteins in diet
holocarboxylase synthetase
attaches biotin to the carboxylases
avidin
in egg whites and attaches to biotin to prevent it from being absorbed by intestine
phenytoin
anti-seizure drug that can lead to biotin or folate deficiency
vitamin B7
biotin
vitamin B9
folate
biotin is found in _
egg yolks, fish, meat, dairy products, nuts, potatoes, broccoli, avocados
folate is found in _
green leafy vegetables, liver, lima beans, whole grains
dihydrofolate reductase
catalyzes conversion of folate to THF
THF function
provides one carbon units for nucleotide synthesis and methylation reactions
folate deficiency
birth defects, no methylation reactions, and megaloblastic anemia
folate deficiency can be due to _
increased folate requirement (pregnancy, smoking), insufficient absorption in intestine (alcohol, certain drugs, Chron’s disease), and increased elimination (liver disease and dialysis)
folate deficiency symptoms
fatigue, gray hair, mouth sores, swollen tongue, forgetfulness, depression, low appetite, low concentration
megaloblastic anemia
due to insufficient THF species for purine and thymidine synthesis; folate requirement is high in hematopoietic cells due to high division rate
megaloblastic anemia can be caused by _
vitamin B9 or vitamin B12 deficiency
How do you differentiate between vitamin B9 or B12 deficiency?
methylmalonic acid will be elevated in vitamin B12 deficiency
folate antimetabolites
antimicrobial; also chemotherapy; enhanced with sulfanilamide
folate cycle provides _
things for nucleotide metabolism and transfers methyl groups to the methionine cycle
methionine cycle provides _
methyl groups for a variety of pathways
What supplies one carbon units to the folate cycle?
degradation of serine, tryptophan, and histidine
What inhibits the folate cycle?
SAM when there are no methyl acceptors
methylene THF reductase
rate-limiting enzyme in folate-methionine bi-cycle
How does SAM regulate its own synthesis?
by inhibiting methylene THF reductase
folate cycle is required for _
dTMP synthesis and purine synthesis
thymidilate synthase
catalyzes synthesis of dTMP from dUMP
high DHF levels
switch folate cycle to DNA synthesis
DHFR is targeted in _
cancer therapy
methotrexate and aminopterin
folate analogs that competitively inhibit DHFR
What happens in the absence of B12?
THF becomes trapped in methyl state and
Where is vitamin B12 found?
animals or fortified sources (cereal)
vitamin B12 absorption
pepsin in the stomach will degrade the proteins bound to B12 –> free B12 will bind to R-factor to protect from stomach acid –> proteases in small intestine will degrade R-factor and vitamin B12 will bind to intrinsic factor –> receptors in ileum will endocytose the complex
pancreatic insufficiency
pancreas will not secrete proteases to digest R-factor, preventing absorption of vitamin B12
cause of vitamin B12 deficiency
poor diet, infection or inflammatory condition, pernicious anemia (antibodies attack parietal cells or intrinsic factor)
vitamin B12 deficiency leads to accumulation of _
homocysteine and methylmalonic acid in urine and inhibition of SAM-mediated methylation reactions and succinyl-CoA
trans-sulfuration pathway
synthesizes cysteine and glutathione
What connects the methionine cycle to the trans-sulfuration pathway?
homocysteine
What can activate the trans-sulfuration pathway?
elevated SAM levels
hyperhomocysteinemia
causes atherosclerosis, thrombosis, heart attack, stroke, dementia, epilepsy, parkinson’s, osteoporosis, eclampsia
defect in homocystinuria
cystathionine beta-synthase which results in accumulation of homocysteine
