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OBJECTIVES
• METABOLISM OF PURINES .

• URINARY EXCERTION OF URATE.

• HYPERURICEMA .

• GOUT .

• HYPOURECEMIA .

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 PURINE METABOLISM
Purine anabolism is essential to the body:
• It provides components of the nucleic acids, DNA
and RNA,
• Energy currency of the cell, ATP & GTP.
• Components of co-enzymes (NAD and FAD)
• Signal transduction (cAMP and cGMPas second
messengers )
Purine catabolism leads to the formation of a
poorly soluble compound, uric acid, which can
precipitate when elevated and causes gout.
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Both DNA and RNA contain the same purine
bases, adenine (A) and guanine (G).
-Purines have 3 sources :
1- Diet.
2- De novo synthesis: nucleotides are synthesized
new from simple precursor molecules.
3-Salvage pathway: (degradation of endogenous
nucleotide).
Purines are derived from inosine-5-mono-
phosphate (IMP).
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I. De-novo synthesis

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The Building Blocks For Purine
Synthesis Are derived from:
• N1: amino group of Aspartate
• C2 & C8: Formate
• N3& N9: amide group of glutamine
• C4, C5 & N7: Glycine
• C6: HCO3-(bicarbonate)

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HMP SHUNT Ribose-5P
De Novo
PRPP
Synthetase Synthesis
PRPP

IMP, GMP, AMP PRPP

amidotransferase

5-
PHOSPORIBOSYLAMINE

Glycine ,asprtate, glutamine

THF as carbon donor

GMP IMP AMP

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HIGH ENERGY COMPOUND
ATP GMP
DNA RNA TURN OVER
HP-Ribose

Pi Ribose-P
NH3
HYPO
AMP ADENOSINE INOSINE XANTHINE

Adenosine
deaminase

Ribose-P
Pi
GMP GUANOSINE GUANINE

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 Salvage pathway
HGPRT
AMP----- IMP
GMP
HYPO-
XANTHINE 90%

GUANINE
XANTHINE URIC ACID

10% Excretion
pathway
Xanthine Lactic acid
compete
Oxidase
with uric for
excretion
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Turn Over or Degradation of Purines

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 2- Salvage Pathway of Purines
• Purines are salvaged by two different enzymes:
1. Adenine phosphoribosyltransferase (APRT):
mediates AMP formation using PRPP
Adenine + PRPP ⇌ AMP + Ppi
2. Hypoxanthine–guanine phosphoribosyl
transferase (HGPRT):, which catalyzes the
analogous reaction for both hypoxanthine and
guanine.
Hypoxanthine + PRPP ⇌ IMP + PPi
Guanine + PRPP ⇌ GMP + PPi
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 Uric Acid Excretion
Uric acid is the end product of purine catabolism
About 1/3 in the gut, metabolized to CO2 and
ammonia by bacterial action (uricolysis).
Other 2/3 by renal excretion, filtered and almost
totally reabsorbed in the PCT .
 Normal urate clearance is 10% , increase of GFR
lead to increase of urate clearance .

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 Hyperuricaemia
• High levels of uric acid in blood, above 7mg/dl in
males & 6mg/dl in females.
• Hyperuracemia is caused by either
overproduction or underexcretion of uric acid or
both of them.
• Humans have higher levels of uric acid because of
a deficiency of the hepatic enzyme, uricase, and a
lower fractional excretion of uric acid.
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 Causes of Hyperuricaemia

1- Causes Of Urate Overproduction:

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 Causes of Hyperuricaemia (cont.)

2- Causes Of Decreased Urate Excretion:

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 Gout
 Hyperuricemia that leads to the deposition of
monosodium urate crystals in joints, and lead to
an inflammatory response to the crystals,
causing first acute and then chronic gouty
arthritis.
 In Chronic Gout, nodular masses of uric acid
crystals deposit in different soft tissue areas of
the body.
 This is known as tophaceous Gout and the uric
acid crystals are called tophi.
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 N.B.
 Hyperuricemia doesn’t always cause gout.
 Over the course of years, sharp urate crystals
build up in the synovial fluid of the joints.
 Precipitating events are infection, surgery,
stress or heavy alcohol drink.

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Types of Gout
“Primary Gout”

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“Primary Gout” cont.

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Types of Gout
“Secondary Gout”

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“Secondary Gout”

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The diagnosis of Gout can be made on the basis of
history, clinical presentation and laboratory tests.

• Patient usually gives a history of the swollen inflamed

joints, starting with the big toe & followed by ankles
and knees, which is recurrent.
• Gout usually involves only a single joint.

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 Diagnosis Of Gout
1. Blood Tests: to confirm hyperuricaemia, but
increased levels may not necessarily be indicative
of Gout.
2. Urine Tests: to measure the amount of uric acid in
a sample of urine collected over 24 hours.
High levels of uric acid in the urine can cause
kidney stones.
3. X-rays: may be helpful and may show uric acid
crystal deposits and bone damage, as a result of
repeated bouts of inflammation of the joints.
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4-Arthrocentesis:
• The best for final
diagnosis.
• Synovial fluid is aspirated
from the joint space and
is seen under microscope
• The presence of fine
needle like uric acid
crystals is diagnostic.
• Monosodium urate(MSU)
crystals.
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 Hypouricemia
 Decreased serum urate <2mg/100ml.
 This is not significant.
 Blood level of uric acid should be followed in
patients who are treated with uricosuric agents
(drugs increase excretion of uric acid in urine).
 Patients with Multiple Sclerosis found to have
low levels of uric acid

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