A 45 year old man awoke from sleep with a painful and swollen right
great toe. On the previous night he had a meal of fried liver and
onions, after which he met with his poker group and drank a number
• He saw his doctor that morning and some tests were ordered. His
serum uric acid level was elevated at 8.0 mg/dl. (What is normal
• The man recalled that his father and his grandfather, both of whom
were alcoholics, often complained of joint pain and swelling in their
What can be his probable diagnosis?
Degradation of Pyrimidines
1. CMP and UMP degraded to bases similarly to purines.
C. Glycosidic bond cleavage
2. Uracil reduced in liver, forming β-Alanine
3. Converted to malonyl-CoA
fatty acid synthesis for
Important points about Uric Acid
1. Final breakdown product of purine degradation in humans.
2. Urates, the ionized forms of uric acid, predominate in
plasma extracellular fluid and synovial fluid, with ~98%
existing as monosodium urate at pH 7.4.
3. Urate is produced only in tissues that contain xanthine
oxidase, primarily the liver and small intestine.
4. Two-thirds to three-fourths of urate is excreted by the
kidneys, and most of the remainder is eliminated through
Important points about Uric Acid (Contd..)
1.Daily synthesis 400mg
2.Dietary sources 300mg
3.Normal uric acid pool: 1200mg in males and 600mg in
4.75% excreted in urine, remainder in GIT where it’s degraded
to Allantoin by bacterial enzymes.
Defined as a plasma urate concentration > 7.0 mg/dl
Increased production of uric acid
• Adenine phosphoribosyl
• Increased phosphoribosyl
• Hemolitic anemia
Decreased excretion of uric acid
• Alterated uric acid excretion could result
from decreased glomerular filtration,
decreased tubular secretion or enhanced
• Diabetic ketoacidosis, starvation,
acidosis, and salicylate intoxication are
accompanied by accumulations of organic
lactate or salicylates) that compete with
urate for tubular secretion.
A defect in production or activity of HGPRT
Causes increased level of hypoxanthine and Guanine (↑ in
degradation to uric acid)
Stimulates production of purine nucleotides (and thereby increases
Causes gout-like symptoms, but also neurological symptoms
spasticity, aggressiveness, self-mutilation, head banging.
First neuropsychiatric abnormality that was attributed to a single
Up to 20 times the uric acid in the urine than in normal individuals.
Uric acid crystals form in the urine.
Life expectancy is early- to mid-20s.
ADENOSINE DEAMINASE DEFICIENCY
In purine degradation, adenosine
ADA deficiency results
inosine enzyme is ADA.
Selectively kills lymphocytes - both b- and t-cells.
Mediate much of immune response.
One of first diseases to be treated with gene therapy.
ADA gene inserted into lymphocytes; then lymphocytes returned
Glucose-6-phosphatase (G6Pase) deficiency
1. Also known as von Gierke's disease.
2. Unable to dephosphorylate G6P.
3. Glucose-6-P goes into Pentose Phosphate shut.
4. Excess production of ribose-5-phosphate.
5. Cause hypoglcemia as liver fails to form glucose from
glycogen. [Glycogen storage disease type I (GSD I)]
Colorimetric determination of uric acid in serum
• Serum is the best, heparinized plasma can be used.
Lipemic and increased bilirubin sample should be avoided.
Drugs such as thiazide and salicyclate cause elevation in uric acid. Why?
Uric acid levels are effected by diet esp. red meat. Why? So will you ask
your patient to fast overnight?
Serum should be separated quickly from whole blood. Why?
1. Chemical method --- phosphotungstic acid method
2. Enzymatic ---- uricase methods.