Question

An infant has an enlarged liver and spleen, cataracts and anaemia and exhibits general
retardation of development. Mevalonate is found in the urine. Investigation reveals a
deficiency of mevalonate kinase, which catalyses the formation of 5-
phosphomevalonate from mevalonate.
11.1. Urinary excretion of mevalonate acid is consistent with a deficiency of
mevalonate kinase. Explain the reason for the deficiency using your own

diagram. 11.2. How would a deficiency of mevalonate kinase affect cholesterol synthesis in this infant? 11.3. What level of HMG-CoA reductase activity, relative to normal, would you expect to find in cells isolated from the infant? Briefly explain your answer.	(5)
(5)
(5)

Answer 1

11.1- mevalonate kinase deficiency is inherited in an autosomal recessive manner.

mutation in mevalonate kinase gene results in mevalonate kinase deficiency.

mevalonate deficiency may clinically present as hyperimmunoglobulinemia D syndrome and mevalonic aciduria.

11.2- mevalonate kinase enzyme is essential in mevalonate pathway. mevalonate pathway produces cholesterol and unsaturated lipid chains called nonsterol isoprenoids.

mevalonate kinase enzyme is responsible for conversion of mevalonate into mevalonate phosphate . Deficiency of mavalonate kinase will results in accumulation of mevalonate and will interfere in cholesterol synthesis.

11.3-

HMG-CoA reductase activity is increased in mevalonate kinase deficiency. activity of HMG-CoA reducatse enzyme is regulated by multivalent feedback mechanism. Isoprenoids suppress the activity of HMG-CoA reductase enzyme. Mevalonate kinase enzyme deficiency results in deficiency of isoprenoids which then results in elevated HMG-CoA reductase activity .