Nitrogen, AAs, and Ntides Flashcards Preview

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Flashcards in Nitrogen, AAs, and Ntides Deck (47)
1

Role of Aminotransferases

Transfer NH3 from AA to alpha-ketoglutarate to turn it into glutamate (and AA become alpha-keto acid)

2

Aspartate Aminotransferase

Unique aminotransferase that transfers NH3 from glutamate to OAA, forming aspartate and alpha-ketoglutarate

3

Aspartate Aminotransferase Cofactor

Vitamin B6 Pyridoxal Phosphate transfers amine in pyridoxamine phosphate form

4

Oxidative Deamination

Glutamate Dehydrogenase catalyzes glutamate conversion to alpha-ketoglutarate w/ release of free NH3

5

Ammonia Transport and Release to/in Liver (3)

Glutamine synthetase adds free NH3 to glutamate in most tissues to create glutamine
Glutamine carries it through blood to liver
Glutaminase and glutamate dehydrogenase remove the two amines in that order to yield glutamate then alpha-ketoglutarate

6

Urea Production Cycle (5 long)

Carbamoyl phosphate synthetase I adds CO2 and NH3 (first two sources of stuff for urea) to form carbamoyl phosphate
Carbamoyl phosphate adds to Ornithine to form Citrulline which can be transported out of mt matrix
Aspartate (source of urea's 2nd N) adds to Citrulline to form arginosuccinate
Fumarate leaves to form Arginine, which has guanidino group head
Guanidino group leaves and becomes urea, leaving ornithine which can be transported back into matrix

7

N-Acetylglutamate (formation and function)

Formed from Arginine-activated Acetyl CoA adding to glutamate
Required to activate carbamoyl phosphate synthetase I for urea production

8

Source of Ammonia in Urine

Glutamate dehydrogenase in kidneys

9

Hyperammonemia (cause, symptom, treatment)

When you have liver disease bc liver is making urea
High glutamine levels in blood
Phenylbutyrate converts into phenylacetate, which can combine w/ glutamine to form phenylacetylglutamine which will be excreted out

10

2 Exclusively Ketogenic AAs

Leu and lys

11

4 Gluco and Ketogenic AAs

Tyr, Ile, Phe, and Trp

12

Degradation of Asn and Asp

Asn converted to Asp converted to OAA (aspartate aminotransferase)

13

Pro, Arg, His, and Gln Degradation

Feed into glutamate can turn into alpha-ketoglutarate for glucogenic effects

14

Ala Degradation

Gives NH3 to alpha-ketoglut (becomes glutamate) to become pyruvate

15

Gly and Ser Degradation

Gly becomes ser via THF-producing rxn, and ser becomes dehydrogenated to pyruvate

16

Phe and Tyr Degradation (2)

Phenylalanine hydroxylase converts Phe to Tyr via Tetrahydrobiopterin putting -OH on phenyl ring
Tyr converted to fumarate and acetoacetate

17

Degradation of Leu, Val, and Ile (3 rxns and 2(3) products)

Transaminated to alphaketoacids
Oxidative decarboxylation to FAs
FAD-linked dehydrogenation
Leu is ketogenic, forms acetoacetate + acetyl CoA
Val and Ile are glucogenic, form succinyl CoA

18

Maple Syrup Urine Disease

Defect in alpha-ketoacid dehydrogenases breaking down the alpha-ketoacids formed from leu/val/ile degradation

19

Met Degradation

Generates SAM which is used as methyl donor for chromatin remodeling/DNA, then converted to Homocysteine which can be reconverted to Met + THF or Serine added to form Cysteine

20

Homocysteine Clinical Consideration

Higher levels correlate w/ cardiovascular problems

21

THF Use

AA and Purine Synth

22

Main Function of Tyr

Hormone Production

23

Dihydrobiopterin (BH2) Reductase Deficiency (action, and 3 clinical effects, and treatment note)

Can't reset BH2 to tetrahydrobiopterin (BH4), causing phenylketouria by messing up phenylalanine hydroxylase
also messes up tyr hydroxylase production of DOPA/CATs and
trp hydroxylase 5-HT production
Difficult to treat bc even if supplement w/ BH4 it can only be used once

24

3 Causes of Phenylketouria (most to least common)

Phenylalanine hydroxylase deficiency
Dihydrobiopterin Reductase Deficiency
GTP Cyclohydrolase Deficiency - can't produce BH2

25

2 Biochemical Effects of Phenylketouria (2.6)

Can't produce tyr from phe, so miss tyr products like melanin, CATs, and fumarate and acetoacetate
Excess phe converted to phenyl pyruvate and then have buildup of toxic organic acids

26

Major Clinical Effect of Untreated Phenylketouria

Progressive severe retardation

27

Albinism Cause

Melanin deficiency from enzyme deficiency to convert bw tyr and melanin

28

Homocystinuria

Cystathione Beta-Synthase Deficiency can't degrade homocysteine

29

Alkaptonuria

Homogentisic Acid Oxidase deficiency causes urine to turn black from oxidation

30

5 Donors to Purine Synth (& what they donate)

Glutamine - 2 Ns
Aspartate - 1 N
Glycine - Backbone of 2Cs and 1N
N-formyl-THF - 2Cs
CO2 - 1C

31

First Step in Base Synthesis

PRPP Synthetase creates 5-Phosphoribosyl-1-pyrophosphate (PRPP) from Ribose 5-P and ATP->AMP

32

Purine Synthesis Mech (general point and 8 steps)

Start w PRPP and build ring around it
Glutamine adds 1st N group
Glycine adds 2C 1N backbone
N-formyl-THF adds C
Glutamine adds 2nd N group
CO2 adds C
Aspartate adds, then leaves N group
N-formyl-THF adds 2nd C
Dehydrated to IMP

33

Methotrexate

Binds and inhibits DHF reductase, preventing reset of THF

34

IMP

Differentiates into AMP and GMP

35

IMP into AMP

Aspartate adds, then leaves just NH2

36

IMP into GMP (2)

Double bond oxidized to carbonyl, then exchanged for NH2 from glutamine

37

3 Donors to Pyrmidine Synth

Aspartate - 1N and 3 Cs
Glutamine - 1N
CO2 - 1C

38

Pyrimidine Synth (major point and 6 steps)

Synthesize ring first then add to PRPP
Carbamoyl phosphate synthetase II creates carbamoyl phosphate from Gln/CO2/ATP
Aspartate adds
Cyclization
Oxidization into orotate
Orotate added to PRPP to create orotidine 5'-monophosphate
Decarbox to UMP

39

CTP Synthesis

CTP Synthetase adds NH2 from Gln to UTP

40

Nucleoside Diphosphate Synthesis

NMP + ATP -> NDP + ADP

41

Salvage Pathways

When bases from diet can be directly added onto PRPP avoiding pathway

42

Ribonucleotide Reductase (2)

Turns ribonucleoside into deoxyribonucleoside via thioredoxin (red-> oxidized)
Thioredoxin reset by the reducing equivalents NADPH

43

Synthesis of dNTP (except TTP)

NDP->dNDP->dNTP

44

Synthesis of (d)TTP

UDP->dUDP but don't need for DNA, so ->dUMP and then thymidylate synthase catalyzes to (d)TMP->TDP->TTP

45

Purine Degradation (3 steps)

AMP and GMP lose ribose 1-P to form hypoxanthine and guanine, respectively
Which then converted to xanthine
Xanthine oxidized to uric acid

46

Gout

Uric acid kept at very high blood concs, so if have problem w/ overproduction or underexcretion it will precipitate and collect in/swell joints

47

Treatment of Gout (w/ 2 different causes of gout)

Overproduction of uric acid - use allopurinol which inhibits xanthine oxidase
Underexcretion - not really treatable, usually caused secondary to some other condition