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MSK > Purine And Uric Acid Metabolism > Flashcards

Purine And Uric Acid Metabolism Flashcards

1
Q

Normal range for Uric acid for women

A

140-369 umol/l

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2
Q

Normal range for Uric acid for men

A

200-430 umol/l

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3
Q

Gout

A

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

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4
Q

Solubility of Uric acid

A

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

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5
Q

pH and Uric acid solubility

A

Lower the pH, less soluble it becomes

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6
Q

What does Uric acid come from

A

Purines

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7
Q

Examples of purines

A

Adenine
Guanine
Hypoxanthine
Xanthine

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8
Q

Sources of purines

A

Diet
Breakdown of nucleotides from tissues
Synthesis in the body

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9
Q

How does Uric acid leave the body

A

Excreted in urine
Breakdown in gut

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10
Q

What percentage of Uric acid leaves the body via urine

A

70%

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11
Q

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

A

30%

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12
Q

Which populations is gout rare in

A

Children
Pre-menopausal women

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13
Q

Why is gout rarer in women

A

Oestrogen promoted Uric acid excretion in urine

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14
Q

Dietary purines

A

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

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15
Q

Risk factors for gout

A

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

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16
Q

Medications that are risk factors for gout

A

Thiazide diuretics
Low dose aspirin
Ciclosporin
Levodopa
Ethambutol
Pyrazinamide

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17
Q

Initial management of gout

A

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

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18
Q

Advice for gout

A

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

19
Q

Newer medications for gout

A

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

20
Q

Preventative medications for gout

A

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

21
Q

Allopurinol mechanism of action

A

Inhibits xantine oxidase
Which converts purines to xanthine to uric acid

22
Q

Conversion of purines to Uric acid

A

Purines —> xanthine —> uric acid

23
Q

Which enzyme catalyses uric acid formation

A

Xanthine oxidase

24
Q

Complications of gout

A

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

25
Q

Complications of high Uric acid

A

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

26
Q

Causes of increased turnover of purines

A

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

27
Q

Rasburicase

A

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

28
Q

Urate-oxidase

A

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

29
Q

Which enzyme recycles hypoxanthine and guanine back to precursors

A

HPRT - hypoxanthine-guanine phosphoribosyl transferase

30
Q

Hyperuricemia

A

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

31
Q

Uric acid metabolism includes which 2 pathways

A

De novo synthesis
Salvage pathway

32
Q

Rate-limiting step of de novo synthesis of purines

A

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

33
Q

What is the initial precursor for purines

A

Ribose-5-phosphate

34
Q

Adenine precursor

35
Q

Guanine precursor

36
Q

Common precursor to all purines at start of salvage pathway

A

Inosine mono phosphate

37
Q

Pyrimidines

A

Thymine
Adenine
Uracil

38
Q

Products of break down of pyrimidines

39
Q

Where are the break down products of pyrimidines excreted

A

Exhalation
In urine

40
Q

Synthesis of RNA

A

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

41
Q

ADA deficiency

A

Inhibition of DNA synthesis
Stops adenosine becoming inosine

42
Q

Lesch-Nyhan syndrome

A

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

43
Q

Synthesis of DNA nucleotide

A

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

MSK (11 decks)

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