Nitrogen, AAs, and Ntides

Question 1

Role of Aminotransferases

Answer 1

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

Question 2

Aspartate Aminotransferase

Answer 2

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

Question 3

Aspartate Aminotransferase Cofactor

Answer 3

Vitamin B6 Pyridoxal Phosphate transfers amine in pyridoxamine phosphate form

Question 4

Oxidative Deamination

Answer 4

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

Question 5

Ammonia Transport and Release to/in Liver (3)

Answer 5

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

Question 6

Urea Production Cycle (5 long)

Answer 6

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

Question 7

N-Acetylglutamate (formation and function)

Answer 7

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

Question 8

Source of Ammonia in Urine

Answer 8

Glutamate dehydrogenase in kidneys

Question 9

Hyperammonemia (cause, symptom, treatment)

Answer 9

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

Question 10

2 Exclusively Ketogenic AAs

Answer 10

Leu and lys

Question 11

4 Gluco and Ketogenic AAs

Answer 11

Tyr, Ile, Phe, and Trp

Question 12

Degradation of Asn and Asp

Answer 12

Asn converted to Asp converted to OAA (aspartate aminotransferase)

Question 13

Pro, Arg, His, and Gln Degradation

Answer 13

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

Question 14

Ala Degradation

Answer 14

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

Question 15

Gly and Ser Degradation

Answer 15

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

Question 16

Phe and Tyr Degradation (2)

Answer 16

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

Question 17

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

Answer 17

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

Question 18

Maple Syrup Urine Disease

Answer 18

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

Question 19

Met Degradation

Answer 19

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

Question 20

Homocysteine Clinical Consideration

Answer 20

Higher levels correlate w/ cardiovascular problems

Question 21

THF Use

Answer 21

AA and Purine Synth

Question 22

Main Function of Tyr

Answer 22

Hormone Production

Question 23

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

Answer 23

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

Question 24

3 Causes of Phenylketouria (most to least common)

Answer 24

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

Question 25

2 Biochemical Effects of Phenylketouria (2.6)

Answer 25

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

Question 26

Major Clinical Effect of Untreated Phenylketouria

Answer 26

Progressive severe retardation

Question 27

Albinism Cause

Answer 27

Melanin deficiency from enzyme deficiency to convert bw tyr and melanin

Question 28

Homocystinuria

Answer 28

Cystathione Beta-Synthase Deficiency can't degrade homocysteine

Question 29

Alkaptonuria

Answer 29

Homogentisic Acid Oxidase deficiency causes urine to turn black from oxidation

Question 30

5 Donors to Purine Synth (& what they donate)

Answer 30

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

Question 31

First Step in Base Synthesis

Answer 31

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

Question 32

Purine Synthesis Mech (general point and 8 steps)

Answer 32

``` 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 ```

Question 33

Methotrexate

Answer 33

Binds and inhibits DHF reductase, preventing reset of THF

Question 34

IMP

Answer 34

Differentiates into AMP and GMP

Question 35

IMP into AMP

Answer 35

Aspartate adds, then leaves just NH2

Question 36

IMP into GMP (2)

Answer 36

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

Question 37

3 Donors to Pyrmidine Synth

Answer 37

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

Question 38

Pyrimidine Synth (major point and 6 steps)

Answer 38

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

Question 39

CTP Synthesis

Answer 39

CTP Synthetase adds NH2 from Gln to UTP

Question 40

Nucleoside Diphosphate Synthesis

Answer 40

NMP + ATP -> NDP + ADP

Question 41

Salvage Pathways

Answer 41

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

Question 42

Ribonucleotide Reductase (2)

Answer 42

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

Question 43

Synthesis of dNTP (except TTP)

Answer 43

NDP->dNDP->dNTP

Question 44

Synthesis of (d)TTP

Answer 44

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

Question 45

Purine Degradation (3 steps)

Answer 45

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

Question 46

Gout

Answer 46

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

Question 47

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

Answer 47

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