Dai

Question 0

Where does amino acid synthesis predominantly occur?

Answer 0

Liver

Question 1

What are the essential amino acids?

Answer 1

WV.MILK.PATH

VP.TALK.WHIM (think Joe Biden)

Question 2

Where do the precursors to the nonessential amino acids come from?

Answer 2

Glucose (intermediates of glycolysis)

Question 3

What is cystinuria?

Answer 3

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.

Question 4

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 _____.

Answer 4

alpha-keto acids, aminotransferases, pyridoxal phosphate (PLP), vitamin B6

Question 5

ALT and AST are aminotransferases (transaminases) that, when present in the blood at elevated levels, indicate ____.

Answer 5

Liver or muscle damage

Question 6

Where does oxidative deamination (of glutamate) occur? What enzyme and cofactors are used?

Answer 6

Mitochondria of liver; glutamate dehydrogenase, NAD+ or NADP

Question 7

PKU is caused by…

Answer 7

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.

Question 8

Albinism is caused by…

Answer 8

Defects in conversion of tyrosine to melanin (possibly tyrosinase step).

Question 9

Alcaptonuria is caused by…

Answer 9

Accumulation of homogentisate due to defect in homogentisate oxidase. (Intermediate in the Tyr -> fumarate/acetoacetate pathway)

Question 10

Maple Syrup Urine Disease is caused by…

Answer 10

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.

Question 11

Nonketotic Hyperglycinemia is caused by…

Answer 11

Defect in glycine cleavage complex and build-up of glycine.

Cleavage complex uses THF.

Question 12

Asparagine is converted to _____ by deamination and then to _____ by deamination (aminotransfer to a-ketoglutarate forming glutamate).

Answer 12

Aspartate, OAA

Question 13

What is the treatment for PKU? If Tyr cannot be synthesized from Phe in PKU, why no albinism?

Answer 13

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.

Question 14

Symptoms of homocystinuria are reminiscent of what disorder?

Answer 14

Marfan Syndrome.

Question 15

Propionyl CoA (3-carbon) is converted to succinyl CoA (4-carbon) using which cofactor and vitamin?

Answer 15

Biotin (for adding CO2), B12 for last step (methylmalonyl CoA mutase)

Question 16

Methylmalonic acidemia/aciduria (MMA) is caused by…

Answer 16

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.

Question 17

Which amino acids have propionyl CoA in there degradation pathway?

Answer 17

Met, Val, Ile, Thr

Question 18

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?

Answer 18

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)

Question 19

How are SAM, THF, and B12 connected to each other?

Answer 19

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).

Question 20

Which enzyme converts dietary folate to THF?

Answer 20

Dihydrofolate reductase (DHFR). Used in cancer chemotherapy (methotrexate)

Question 21

Which heme isomer is used in biosynthetic pathways?

Answer 21

Asymmetric

Question 22

What goes into heme synthesis?

Answer 22

8 glycine, 8 succinyl CoA, Fe2+

Question 23

What is the rate-limiting step in heme synthesis? How is it regulated?

Answer 23

The first step (gylcine + succinyl CoA = ALA), catalyzed by ALA synthetase. End-product inhibition by heme.

Question 24

In porphyria, deficiencies in the early steps of heme synthesis lead to _____ symptoms while deficiencies in later steps lead to ____ symptoms.

Answer 24

Neuropsychiatric, cutaneous (deposits in skin, photosensitivity)

Question 25

In acute intermittent porphyria (AIP), ____ is defective, causing an accumulation of ____ and ____.

Answer 25

PBG deaminase, ALA, PBG (both are neurotoxic)

Question 26

How is AIP treated?

Answer 26

Treat precipitating infection
Avoid precipitating drugs
Prevent acidosis by giving high-carb diet
IV heme, which inhibits step #1 and will reduce ALA and PBG levels

Question 27

Porphyria cutaneous tarda is marked by accumulation of ____ in the skin, which is oxidized to _____.

Answer 27

Uroporphyrinogen III, uroporphyrin (causes photosensitivity)

Question 28

How is PCT treated?

Answer 28

Avoid alcohol and other risk factors
Avoid sunlight
Give chloroquine, which complexes with porphyrins and promotes excretion
Give b-carotene, eliminates free radicals