Disorders of uric acid metabolism/Questions and case studies

Questions[edit | edit source]

In humans, carbamoyl phosphate is a precursor for the biosynthesis of:
- A – uridine monophosphate
- B – Inosine monophosphate
- C – urea
- D – glutamine
The metabolites of vitamin B₁₂ 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 – During the transfer of the CH₃- group from tetrahydrofolate coenzyme to homocysteine
- D – In the synthesis of palmitate
All of the statements below regarding purine biosynthesis nucleotides are correct except:
- A – PRPP is a substrate in this metabolic pathway
- B – 2 nitrogen atoms of the purine cycle are formed from glutamine
- C – Formation of N-glycosidic bond only after completion of base structure
- D – Folate cofactors are involved in the carbons of the purine cycle
- E – Inosine monophosphate is a precursor to 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. To recognize this situation, ¹⁵N-labeled amino acid can be administered. Which one 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 UMP intermediates (pyrimidine nucleotide biosynthesis)

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

C – Yes. Detoxification of NH4+ in the liver occurs in the cycle of urea formation, the beginning of which is carbamoyl phosphate (CO₂ + NH⁴⁺ + ATP).

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

Question 2.

A – Yes. It is not acetoacetyl-CoA, 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 requires another vitamin: thiamine and pantothenate.

C – Yes. In the conversion of homocysteine to S-adenosylmethionine, vitamin B₁₂ is needed as a cofactor.

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

Question 3.

A – Wrong
B – Wrong

C – Correct

D – Wrong
E – Wrong.

Question 4.

Glycine. Its entire molecule is incorporated into the precursor of purine nucleotides during biosynthesis. Glycine nitrogen also appears in uric acid.

Case reports[edit | edit source]

Female patient treated for acute leukemia[edit | edit source]

A 3-year-old girl was admitted with a diagnosis of acute lymphocytic leukemia. She received IVs, allopurinol, 2nd day of vincristine therapy, prednisone, methotrexate, etc. Discharged home in 5 days. She continued therapy at home (prednisone, allopurinol). Added chemotherapy again in a month. Then she gotthrush 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 (count/ml of blood)

Questions:

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

Answers

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

Links[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.