Vitamin Deficiency & One Carbon Unit Metabolism Flashcards
Enzymes requiring thaimin & def diseases
PHD, a-ketoglutarate dehydrogenase (osidative decarboxylation), transketolase, branched chain ketoacid dehydrogenase
Wernike-Korsakoff (psychosis & encephalitis), acute def in alcoholics
Beriberi (wet & dry)
Thiamin forms coezyme ….. by ………
TPP
ATP dependant reaction in brain & liver
Mention tests for thiamin status
Blood thiamin
Urine thiamin
Erythrocyte transketolase activity
Thiamin pyrophosphate effect
Blood pyruvate & lactate
Biochemical basis & CP of Pyruvate dehydrogenase deficiency
Pyruvate isn’t converted to acetylCoA, production of citrate is limited thus TCA cannot proceed. An energy deficit occurs
CP, lactic acidosis due to divergence of pyruvate to other pathways
Neurological form contributes to hypotonia, poor feeding, lethargy, structural brain abnormalities leads to mental retardation, microcephaly, blindness, spasticity.
Treatment of PDH def
Dietary restriction of carbs
Correction of acidosis
Niacin chemical structure is ……
Pyridinine 3-carboxylic acid
Mention sources of niacin
Food, unrefined grains, milk, lean meat.
Tryptophan
Mention a therapeutic use of niacin
Lowers plasma cholesterol and TAGs as it strongly inhibits lipolysis in adipose tissue, thus dec circulating FFAs
Symptoms and causes of pellagra
S, dermatitis, diarrhea, dementia, death
C, diet poor in tryptophan and niacin, defective absorption as Hartnup disease, B6 def, carcinoid tumour.
Describe chemical composition of folic acid
Pteridine ring +pABA+glutamate
Describe the reaction of folate activation
By two sequential steps both are NADPH+H+ rewuiring enzymes: folate reductase and dihydrofolate reductase.
Sulfa drugs inhibit ….. while trimethoprim inhibits …..
Folic acid synthesis
Dihydrofolate reductase
Mention the metabolic role of tetrahydrofolate
Carrier of one carbon unit for synthesis of choline, serine, glycine, methionine, purines.
List Most reduced, intermediate and most oxidized one carbon units respectively
Methyl
Methylene
Formyl formimino methenyl
One carbon uits can be carries by …
THF
SAM
CO2 is carried by …
Biotin
One C units are linked to THF at
N5
N10
Both
Interconversion of 1C unit occurs by enzymes….&….
NAD-dehdrogenase
NADP-reductase
Sources and fate of methylene group
S, b-carbon of serine, glycine by glycine cleavage system
F, oxidized to methenyl-THF, reduced to methyl-THF, thymidylate synthesis.
Sources and fate of methenyl group
S, histidine –>figlu–>5-formimino THF–> 5,10 methenyl THF
Oxidation of methylene THF
F, hydrolysed to N10 formyl THF
Sources and fate of formyl group
S, activation of free formate by ATP (Formyl THF synthetase), hydrolysis of methenyl THF, Tryptophan catabolism.
F, synthesis of C2, C8 in purines
Sources and fate of methyl THF
S, by reduction of methylene THF catalyzed by methylene THF reductase (NAD-linked)
Fate, vit B12 coenz, accept CH3 to form methylcobalamin then transfer it to homocysteine to form methionine
Explain methyl trap
Def of B12 in which THF is converted to methyl THF which thereafter has no way of being metabolized and serves as a sink of THF that causes a subsequent deficiency of folate.
