Purine And Uric Acid Metabolism

Question 1

Normal range for Uric acid for women

Answer 1

140-369 umol/l

Question 2

Normal range for Uric acid for men

Answer 2

200-430 umol/l

Question 3

Gout

Answer 3

High Uric acid levels in the blood cause urate/Uric acid crystals to deposit in joints
Crystals cause inflammation which then causes swelling, pain and redness

Question 4

Solubility of Uric acid

Answer 4

Poorly soluble in plasma
The lower the pH the less soluble it becomes

Question 5

pH and Uric acid solubility

Answer 5

Lower the pH, less soluble it becomes

Question 6

What does Uric acid come from

Answer 6

Purines

Question 7

Examples of purines

Answer 7

Adenine
Guanine
Hypoxanthine
Xanthine

Question 8

Sources of purines

Answer 8

Diet
Breakdown of nucleotides from tissues
Synthesis in the body

Question 9

How does Uric acid leave the body

Answer 9

Excreted in urine
Breakdown in gut

Question 10

What percentage of Uric acid leaves the body via urine

Answer 10

70%

Question 11

What percentage of Uric acid leaves the body via breakdown in gut

Answer 11

30%

Question 12

Which populations is gout rare in

Answer 12

Children
Pre-menopausal women

Question 13

Why is gout rarer in women

Answer 13

Oestrogen promoted Uric acid excretion in urine

Question 14

Dietary purines

Answer 14

Meat
Offal - heart, liver and kidney
Seafood - mussels
Fish -herring and sardines
Oatmeal, soya and yeast extracts
Fructose

Question 15

Risk factors for gout

Answer 15

Metabolic syndrome- obesity, raised triglycerides, raised blood pressure
Coronary heart disease
Diabetes
Alcohol- mainly beer, spirits and port wine
Reduced kidney function

Question 16

Medications that are risk factors for gout

Answer 16

Thiazide diuretics
Low dose aspirin
Ciclosporin
Levodopa
Ethambutol
Pyrazinamide

Question 17

Initial management of gout

Answer 17

Rest
Ice pack
Elevate affected joint
Anti-inflammatory medication- NSAID eg ibuprofen

Question 18

Advice for gout

Answer 18

Advise patient to reduce alcohol
Avoidance purine rich food
Loose weight
Keep well hydrated
Check/change blood pressure medication

Question 19

Newer medications for gout

Answer 19

Canakinumab
Monoclonal antibody
Inhibits pro-inflammatory cytokine IL-1
Other newer drugs: anakinra & rilonacept

Question 20

Preventative medications for gout

Answer 20

Allopurinol
If two or more attacks within a year
Should not be started during acute attacks
Give anti-inflammatory when starting treatment

Other options: febuoxstat, sulfinpyrazone

Question 21

Allopurinol mechanism of action

Answer 21

Inhibits xantine oxidase
Which converts purines to xanthine to uric acid

Question 22

Conversion of purines to Uric acid

Answer 22

Purines —> xanthine —> uric acid

Question 23

Which enzyme catalyses uric acid formation

Answer 23

Xanthine oxidase

Question 24

Complications of gout

Answer 24

Damage to the joint (degenerative arthritis)
Secondary infections
Nerve damage

Question 25

Complications of high Uric acid

Answer 25

Kidney stones- urate crystals can form in the kidneys Gouty tophi - urate crystals deposited in soft tissues

Question 26

Causes of increased turnover of purines

Answer 26

Rapidly growing malignant tissue Increased tissue breakdown eg trauma or starvation Psoriasis

Question 27

Rasburicase

Answer 27

Enzyme not present in humans and primates - urate-oxidase Present in other mammals Rasburicase is a recombinant form of urate-oxidase

Question 28

Urate-oxidase

Answer 28

Converts Uric acid to allantoin which is more soluble so more easily excreted

Question 29

Which enzyme recycles hypoxanthine and guanine back to precursors

Answer 29

HPRT - hypoxanthine-guanine phosphoribosyl transferase

Question 30

Hyperuricemia

Answer 30

due to over-production or under-excretion of uric acid or due to a combination

Question 31

Uric acid metabolism includes which 2 pathways

Answer 31

De novo synthesis Salvage pathway

Question 32

Rate-limiting step of de novo synthesis of purines

Answer 32

Phosphoribose 1 pyrophosphate —> 5’ phosphoribosylamine Catalysed by PRPP amido transferase

Question 33

What is the initial precursor for purines

Answer 33

Ribose-5-phosphate

Question 34

Adenine precursor

Answer 34

AMP

Question 35

Guanine precursor

Answer 35

GMP

Question 36

Common precursor to all purines at start of salvage pathway

Answer 36

Inosine mono phosphate

Question 37

Pyrimidines

Answer 37

Thymine Adenine Uracil

Question 38

Products of break down of pyrimidines

Answer 38

CO2 NH3

Question 39

Where are the break down products of pyrimidines excreted

Answer 39

Exhalation In urine

Question 40

Synthesis of RNA

Answer 40

Ribose-5-phosphate and A/U/C/G

Question 41

ADA deficiency

Answer 41

Inhibition of DNA synthesis Stops adenosine becoming inosine

Question 42

Lesch-Nyhan syndrome

Answer 42

No HGPRT which. Is used in the recycling of guanine and hypoxanthine Means more purines are excreted in urine

Question 43

Synthesis of DNA nucleotide

Answer 43

Starts with diphosphates of RNA molecules Ribonucleotide diphosphate reductase reduces ribose to deoxyribose Molecules then lose phosphate groups to become d?MP Thymidylate synthetase converts dUMP into dTMP