Purines/Pyrimidines, AA Synthesis and Metabolism, Catecholamines

Question 1

First step of purine synthesis

Answer 1

Ribose 5 Phosphate (pentose phosphate pathway) comes 5-phosphoribosyl-1-pyrophosphate (PRPP) using ATP via PRPP synthetase. Inhibited by IMP, GMP, AMP.

Question 2

Amidophosphoribosyl transferase reaction

Answer 2

Second step of purine synthesis, also the rate limiting step. PRPP + Glutamine –> 5 phosphoribosylamine via amidophosphoribosyl transferase. 5 Phosphoribosylamine becomes Inosine monophosphate eventually (which has hypoxanthine as its base). Inhibited by IMP, AMP, and GMP.

Question 3

AMP Synthesis

Answer 3

IMP + Aspartate +GTP –> Adenosuccinate –> AMP + Fumarate. This reaction is inhibited by AMP.

Question 4

GMP Synthesis

Answer 4

IMP + NAD –> Xanthylate

Xanthylate + Glutamine + ATP –> GMP + Glutamate. This reaction is inhibited by GMP.

Question 5

How do XMP’s become XDP’s?

Answer 5

Easily, utilizing nucleoside monophosphate kinase.

Question 6

How do XDP’s become XTP’s?

Answer 6

Easily, utilizing nucleoside diphosphate kinase.

Question 7

Salvage Pathway Purpose

Answer 7

When purines are degraded to free bases, they can be salvaged rather than excreted.

Question 8

Salvage Pathway for A

Answer 8

Adenine + PRPP —> AMP + PPi Via Adenine phosphoribosyl transferase

Question 9

Salvage Pathway for G/Xanthine

Answer 9

Guanine/Hypoxanthine + PRPP –> GMP/IMP + PPi via hypoxanthine/guanine phosphoribosyl transferase.

Question 10

Lesch-Nyhan Syndrome

Answer 10

HGPRT deficiency

Question 11

Purine Metabolism

Answer 11

Guanine –> Xanthine –> Uric Acid

Adenine –> Hypoxanthine –> Xanthine –> Uric acid

Question 12

Purpose of Uric Acid

Answer 12

To neutralize ROS in blood

Question 13

Gout

Answer 13

Uric Acid Crystals cause inflammation

Question 14

Pyrimidine Synthesis First Step

Answer 14

Glutamine + CO2 –> Carbamoyl Phosphate via CPS II

Question 15

CPS II and reaction

Answer 15

Found in the cyto of all cells, not only in liver mitochondria like CPS I. Not increased by NAGA.
Glutamine + CO2 –> Carbamoyl Phosphate

Question 16

Rate Limiting Step of Pyrimidine Synthesis

Answer 16

Carbamoyl Phosphate + Aspartate –> N-Carbamoyl Aspartate (via Aspartate Transcarbamoylase)

Question 17

N-Carbamoyl Aspartate

Answer 17

Makes UMP, which makes UDP, which makes UTP

Question 18

How does UTP become CTP?

Answer 18

UTP + Glutamine –> CTP + Glutamate

Question 19

Orotate

Answer 19

Intermediate in pyrimidine synthesis. Accumulates in people with Ornithine Transcarbamylase deficiency.

Question 20

Deoxyribose Formation

Answer 20

Ribose –> Deoxyribose, but not the other way around. Occurs via ribonucleotide reductase.

Question 21

Ribonucleotide Reductase Structure

Answer 21

B1 has overall activity site and specificity site. B2 has catalytic site with tyrosines and thiols

Question 22

How does RR work?

Answer 22

Using a tyrosine to create a radical. Thiols will be oxidized, then reduced by thioredoxin, thioredoxin reductase, FADH2, NADPH.

Question 23

How is RR regulated at the overall activity site?

Answer 23

Increased activity by ATP, shut down by dATP.

Question 24

C3 Family of AA’s

Answer 24

Alanine, Tryptophan (becomes Alanine and acetyl CoA), Glycine, and Cysteine

Question 24

How is RR regulated at the specificity site?

Answer 24

ATP generates d Pyrimidines. dTTP decreases pyrimidines and increases dGTP synthesis. dGTP causes dATP generation, which shuts down the mechanism.

Question 25

Alanine Metabolism

Answer 25

Alanine + AKG --> Pyr + Glu via GPT

Question 26

Glycine Metabolism

Answer 26

Glycine--> Serine (Via Serine Transhydroxymethylase) | Serine --> Pyruvate

Question 27

Cysteine Metabolism

Answer 27

Cysteine --> Pyruvate + S

Question 28

C4 Family of AA's

Answer 28

Aspartate, Asparagine, Methionine, Valine, Threonine, Isoleucine

Question 29

Aspartate Metabolism

Answer 29

Aspartate + AKG --> Glutamate + OAA via GOT

Question 30

Asparagine Metabolism

Answer 30

Asparagine --> Aspartate + NH3 via Asparaginase

Question 31

Methionine, Valine, Threonine, Isoleucine Metabolism

Answer 31

Become propionyl CoA --> Methylmalonyl CoA --> Succinyl CoA

Question 32

C5 family of AAs

Answer 32

Glutamate, Glutamine, Histidine, Arginine

Question 33

Glutamate Metabolism

Answer 33

Glu + NAD --> AKG + NH3

Question 34

Glutamine Metabolism

Answer 34

Glutamine --> Glutamate + NH3 via Glutaminase

Question 35

Histidine Metabolism

Answer 35

Histidine become formamino glutamine, which becomes formamino THF

Question 36

Arginine Metabolism

Answer 36

Arginine --> Urea + Ornithine via Arginase

Question 37

BCAAs and their metabolism

Answer 37

Valine, Isoleucine, Leucine undergo transamination with AKG to form their respective alpha ketoacid. This is then decarboxylated by BCAlphaKetoacid Dehydrogenase to create CoA and CO2. This second reaction uses a E3 mechanism like pyruvate dehydrogenase.

Question 38

Phenylalanine Metabolism

Answer 38

Phenylalanine + Tetrahydrobiopterin + O2 --> Tyrosine via Phenylalanine Hydroxylase

Question 39

PKU

Answer 39

Caused by a deficiency in Phenylalanine Hydroxylase

Question 40

Tyrosine Metabolism

Answer 40

Tyr --> Fumarate and Acetoacetate

Question 41

Mixed Function Oxidation

Answer 41

Where the atoms of an O2 are split up into different products.

Question 42

Catecholamine Synthesis

Answer 42

Occurs in adrenals. Tyrosine --> DOPA (Via tyrosine hydroxylase and THB) --> Dopamine (via DOPA decarboxylase) --> NE (Via DA Betahydroxylase) --> Epi (Via SAM methyltransferase)

Question 43

5-HT Synthesis

Answer 43

Tryptophan --> 5HTP (Via Tryptophan Hydroxylase + THB) --> 5-HT (via DOPA decarboxylase) --> NAcetylSerotonin --> Melatonin

Question 44

What three amino acids make up Glutathione?

Answer 44

Glutamate, Cystine, Glycine