Dai Flashcards
(29 cards)
Where does amino acid synthesis predominantly occur?
Liver
What are the essential amino acids?
WV.MILK.PATH
VP.TALK.WHIM (think Joe Biden)
Where do the precursors to the nonessential amino acids come from?
Glucose (intermediates of glycolysis)
What is cystinuria?
Inability to reabsorb cystine and basic amino acids in proximal convoluted tubules of kidneys, leading to cystine stones in urinary tract. Caused by COAL transporter defect.
In nitrogen disposal of amino acid amine groups, transamination occurs between the amino acid and ______, catalyzed by _______ enzymes, using _____ as a cofactor, which is derived from _____.
alpha-keto acids, aminotransferases, pyridoxal phosphate (PLP), vitamin B6
ALT and AST are aminotransferases (transaminases) that, when present in the blood at elevated levels, indicate ____.
Liver or muscle damage
Where does oxidative deamination (of glutamate) occur? What enzyme and cofactors are used?
Mitochondria of liver; glutamate dehydrogenase, NAD+ or NADP
PKU is caused by…
Defect in conversion of phenylalanine to tyrosine. Catalyzed by Phe hydroxylase, using tetrahydrobiopterin (BH4) as a cofactor and NADH to recycle BH4. (Either the enzyme or BH4 can be defective in PKU)
Phe accumulates, Tyr low.
Albinism is caused by…
Defects in conversion of tyrosine to melanin (possibly tyrosinase step).
Alcaptonuria is caused by…
Accumulation of homogentisate due to defect in homogentisate oxidase. (Intermediate in the Tyr -> fumarate/acetoacetate pathway)
Maple Syrup Urine Disease is caused by…
Defect in catabolism of BCAAs (Val, Iso, Leu) to succinyl CoA and acetyl CoA. First they undergo transamination to form a-keto acids, then oxidative decarboxylation by BCKA dehydrogenase. This step is defective in MSUD. TPP is a cofactor.
Nonketotic Hyperglycinemia is caused by…
Defect in glycine cleavage complex and build-up of glycine.
Cleavage complex uses THF.
Asparagine is converted to _____ by deamination and then to _____ by deamination (aminotransfer to a-ketoglutarate forming glutamate).
Aspartate, OAA
What is the treatment for PKU? If Tyr cannot be synthesized from Phe in PKU, why no albinism?
No phenylalanine in diet (if the problem is with the enzyme – if BH4 is defective, give BH4 supplements). No albinism because tyrosine can still come from diet. It becomes an essential AA.
Symptoms of homocystinuria are reminiscent of what disorder?
Marfan Syndrome.
Propionyl CoA (3-carbon) is converted to succinyl CoA (4-carbon) using which cofactor and vitamin?
Biotin (for adding CO2), B12 for last step (methylmalonyl CoA mutase)
Methylmalonic acidemia/aciduria (MMA) is caused by…
Deficiency in methylmalonyl CoA mutase, the final enzyme in the conversion of propionyl CoA to succinyl CoA, or its coenzyme, B12, leading to accumulation of methylmalonic acid.
Which amino acids have propionyl CoA in there degradation pathway?
Met, Val, Ile, Thr
The one-carbon carriers transfer carbon in three ways:
1) as -CH3 (most reduced)
2) as CO2 (most oxidized)
3) as everything in between
What are their carriers?
1) THF, SAM, B12
2) Biotin
3) THF
*THF-C-X are active THFs that can be used for purine/thymidine synthesis, except for THF-CH3, which is the “storage” form that can only participate in Met salvage. (Homocysteine –> Met)
How are SAM, THF, and B12 connected to each other?
Met salvage. Methionine becomes SAM on its way to homocysteine. B12-CH3 transfers its methyl group to homocysteine to regenerate Met. THF-CH3 regenerates B12-CH3 (methyl transfer).
Which enzyme converts dietary folate to THF?
Dihydrofolate reductase (DHFR). Used in cancer chemotherapy (methotrexate)
Which heme isomer is used in biosynthetic pathways?
Asymmetric
What goes into heme synthesis?
8 glycine, 8 succinyl CoA, Fe2+
What is the rate-limiting step in heme synthesis? How is it regulated?
The first step (gylcine + succinyl CoA = ALA), catalyzed by ALA synthetase. End-product inhibition by heme.
