Purine Pyrimidine metabolism

Question 1

What percentage of dietary nucleotides do we use for energy?

Answer 1

less than 5%

about 95% of all nucleotides used in our cells is derived from de novo synthesis

Question 2

Sources of nucleotides?

Answer 2

dietary (small amount)
De novo synthesis (large amount)
nucleic acid degradation
Nuceloside degredation (salvage pathway)
-can be excreted this way, breaks down into sugar and base

Question 3

Purines?

Answer 3

G A

Question 4

what rate determining enzyme is responsible for the synthesis of ribose-5-phosphate?

Answer 4

G6PD

Question 5

Phosphoribosyl pyrophosphate? (PRPP)

Answer 5

ribose-5-phosphate to 5-phosphoribosyl-p-pyrophosphate

Question 6

Rate limit step for purine production?

Answer 6

GLN-PRPP aminotransferase

5-phosphoribosyl-p-pyrophosphate to 5-phosphoribosylamine

Question 7

Dividing step between ATP and GTP?

Answer 7

IMP
Adenylosuccinate synthase, makes Adenylosuccinate to make ATP

dehyrogenase I makes XMP, to make GTP

Question 8

Purine salvage pathway?

Answer 8

Purines will do on to make Hypoxanthine guanine, and then onto to uric acid

HGPRT recycles Hypoxanthine guanine back into nucelotides

Question 9

Deficiency in HGPRT?

Answer 9

this is called Lesch-Nyhan syndrome, a gentetic deficiency in this enzyme
can’t resalvage the nucelotides and therefore make uric acrd

Question 10

Lesch-Nyhan Syndrome?

Answer 10

results from def in HGPRT
occurs in about 1 in 100, 000 live births
causes hyperuricemia and markedly increased uric aciduria
leads to juvenile onset of uric acid stone formation and gouty arthritis
self injurious behavior (self mutilation)

Question 11

HGPRT degredation?

Answer 11

Hypoxanthine back into IMP

Guanine back into GMP

Question 12

Bubble boy syndrome/ SCIDS?

Answer 12

severe combined immunodeficiency syndrome (SCIDs)

Question 13

SCIDS?

Answer 13

deletion or mutation of adenosine deaminase results in this
accounts for nearly 15-20% of all SCID cases
deficiency is rare
infants inherited with an ADA deficiency have profound lymphocyte depletion, lack both cellular and humoral immune function

Question 14

ADA?

Answer 14

adenosine deaminase
Adenosine to Idosine
without can’t degrade adenosine

Question 15

Build up of adenosine from bubble boy causes?

Answer 15

increase in dATP, to shut off ribonucleotide reductase, can’t make dATP, dGTP, dCTP, can’t make B cells, T cells
receptor for ribonucleotide reductase shuts off with hight amounts of dATP

Question 16

Formation of uric acid?

Answer 16

Xanthine (cross between both pathways of adenosine and guanine)
makes uric acid (xanthine oxidase)

Question 17

Gout?

Answer 17

caused by overproduction or decreased excretion of uric acid
excess uric acid crystals precipitate
crystal formation sets off a series of inflammatory mediators (IL-1, IL-6, IL-8, TNFalpha)

Question 18

Excretion of Uric acid?

Answer 18

through tubular epithelial cells, URAT1 (urate transporter) this helps reabsorb uric acid
urate into tubular filtrate

Question 19

Block URAT1?

Answer 19

decreases reabsorption of uric acid, increasing excretion

Question 20

Causes of hyperuricemia?

Answer 20

obesity
hyperparathyoridism
hypoparahyroidism
hypothyroidism
hyperthyoridism
sepsis
renal insufficiency
etc

Question 21

Effects of fructose on uric acid levels?

Answer 21

high fructose, cause increase in uric acid

Fructose uses ATP to make fructose-1-P and makes ADP, ADP is a precursor to making uric acid

Question 22

Pathophysiology of Uric acid accumulation?

Answer 22

Monosodium urate crystals through a few means cause Caspase-1 to be made
this causes IL-1beta to be made, causing more to be made, also makes TNF and IL-6 (proinflammatory factors)

Question 23

3 ways monosodium urate crystals cause inflammation?

Answer 23

1. NADPH oxidase, increase ROS
2. bind to CD14/TLR2/4
3. K depletion

Question 24

Other things urate crystals do?

Answer 24

complement activation, mast cells
activation of resident synovial cells
-neutrophil influx and chemotaxis

Question 25

Neutrophil partially ingests a urate crystal?

Answer 25

neturophil activation
neutrophil lysis

further neutrophil influx, inflammation and joint damage

Question 26

Neutrophils release?

Answer 26

IL-18, IL-8, LTB4 release, Degranulation, Reactive oxygenation generation

Question 27

Pyrimidines?

Answer 27

2 rings, 2 amino acids (glutamine, aspartate)
one pathway to make both

C T

Question 28

Carbamoyl phosphate?

Answer 28

made from gluatamine, CO2, ATP — CPS-II

Question 29

Biochemistry of ribonucleotide reductase?

Answer 29

ADP, CDP, GDP, UDP—-(ribonucleotide reductase)– dADP, dCDP, dGDP, dUDP

Question 30

how do we synthesize TTP?

Answer 30

Thymidylate synthase (dUMP- dTMP)

Question 31

Dihydrofolate reductase?

Answer 31

dihydrofolic acid to tetrahydrofolic acid (THF)

stop cell growth, shut off rapid proliferative cancer

Question 32

Ethanol and uric acid?

Answer 32

ATP depletion
lactate levels, decrease release uric acid
increase renal retention uric acid
increase purines (in ethanol)

Question 33

Some things to decrease gout?

Answer 33

exercise decreases gout
dilute with water, stay hydrated
limit fructose intake
meds