Disorders of uric acid metabolism / Questions and case reports

Questions[edit | edit source]

In humans, carbamoyl phosphate is a precursor of biosynthesis:
- A – uridine monophosphate
- B – Inosine monophosphate
- C – urea
- D – glutamine
vitamin B₁₂ metabolites play a role in
- A – Catabolism of fatty acids with an odd number of carbon atoms
- B – In the formation of acetyl-CoA from pyruvate
- C – In the transfer of the CH₃- group from the tetrahydrofolate coenzyme to homocysteine
- D – In the synthesis of palmitate
All of the following statements relating to purine nucleotide biosynthesis are correct except:
- A – PRPP is a substrate in this metabolic pathway
- B – Glutamine forms 2 nitrogen atoms of the purine cycle
- C – Formation of N-glycosidic bond only after completion of the base structure
- D – Folate cofactors are involved in the carbons of the purine cycle
- E – Inosine monophosphate is a precursor of both AMP and GMP.
Gout is caused by an excessive increase in the concentration of uric acid in the blood. The cause can be both overproduction and insufficient excretion. A 15N-labeled amino acid can be administered to recognize this situation. Which is best for this purpose?

Answers

Question 1.

A – Yes. Carbamoyl phosphate first gives carbamoyl aspartate with aspartate, which is converted to orotic acid and this via several intermediates UMP (pyrimidine nucleotide biosynthesis)

B – Incorrect. Inosine monophosphate is formed from PRPP (purine nucleotide biosynthesis)

C – Yes. NH4 + detoxification in the liver occurs in the urea cycle, which is initiated by carbamoyl phosphate (CO₂ + NH⁴⁺ + ATP).

D – Incorrect. Glutamine is formed from glutamate, which thus fixes inorganic NH⁴⁺ to the amide group (NH⁴⁺ detoxification in cells)

Question 2.

A – Yes. Not acetoacetyl-CoA is formed, but propionyl-CoA, which is converted to succinyl-CoA. The reaction needs biotin and vitamin B₁₂.

B – No. Oxidative decarboxylation of pyruvate to acetyl-CoA needs a different vitamin: thiamine and pantothenate.

C – Yes. Vitamin B₁₂ is required as a cofactor in the conversion of homocysteine to S-adenosylmethionine.

D – No. Palmitic acid has an even number of carbons and β-oxidation gives a 4-carbon fragment, not 3-carbon as fatty acids with an odd number of C-atoms.

Otázka 3.

A – Wrong
B – Wrong

C – Right

D – Wrong
E – Wrong.

Otázka 4.

Glycine. Its entire molecule is incorporated into the purine nucleotide precursor during biosynthesis. Glycine nitrogen also occurs in uric acid.

Case reports[edit | edit source]

A patient being treated for acute leukaemia[edit | edit source]

A 3-year-old girl is diagnosed with acute lymphocytic leukaemia. She received an infusion, allopurinol, day 2 therapy vincristine, prednisone, methotrexate, etc. In 5 days released home. She continued therapy at home (prednisone, allopurinol. Chemotherapy added again in a month. Then she got soor (candidosis) in her mouth, she couldn't eat.

Laboratory results (gradually during the month):
S-urea	4,0	5,0	1,3	0,7 (mmol/l)
S-creatinine	62	88	62	62 (μmol/l)
S-uric acid	714	547	238	113	137	184 (μmol/l)
white blood cells	56 300	3 700	2 800	3 700 (no./ml in blood)

Questions:

How do you explain the high level of uric acid (1st examination performed after 5 days of hospitalization, after discharge)?
Why was uric acid already normal in future examinations?
Why was the urea level 0.7 mmol / l?
What other tests will confirm this finding?

Answers

The breakdown of white blood cells leads to an increased breakdown of purine substances. It was not a renal cause because urea + creatinine was normal.
Due to chemotherapy, the number of white blood cells decreased and uric acid decreased due to allopurinol.
Based on reduced protein intake (the patient did not eat-soor-suppress proteosynthesis in the liver).
Determination of total protein and albumin should yield low values.

References[edit | edit source]

Source[edit | edit source]

MASOPUST, Jaroslav – PRŮŠA, Richard. Patobiochemie metabolických drah. 1. edition. Praha : Univerzita Karlova, 1999. 182 pp. pp. 113- 114. ISBN 80-238-4589-6.