Question

Biochemistry problem
A 1-month-old girl shows signs of hypotonia, lactic academy, and
pyruvatic, cerebral atrophy and delay in its development. At 3 months studies
show abnormally high amounts of fumarate and succinate in the urine,
fumarate was particularly high. A biopsy of the muscle mitochondria e
liver revealed problems with the oxidation of glutamate or succinate by
muscle mitochondria, while the liver oxidized these substrates in a way
normal. However, fumarase activity was absent in both mitochondria
of the liver and muscles. Cytoplasmic fumarase was also absent in
both tissues. The patient died at 5 months. The patient was diagnosed with
a mitochondrial myopathy that affects the muscles and brain.

a) What reaction catalyzes fumarase

b) In this case, the diagnosis took a long time and the fumarase deficiency was
recognized too late to start appropriate treatment. Knowing the defect
biochemist of this patient which therapy would you suggest?

c) Provides an explanation for the normal oxidative activity of the mitochondria of the
liver compared to damaged muscle mitochondria. Consider that the
liver is a highly biosynthetic organ (biosynthesis), while the muscle is
a lot less.

Answer 1

A- a) Fumarase catalyse the conversion of fumurate to Malate.

b) Early diagnosis reveal the signs of hypotonia, lactic academy, and pyruvatic, cerebral atrophy and delay in its development. Supportive and symptomatic treatment can be given. Since there are no such specific therapy for the cure of cerebral atrophy. Some symptoms of underlying causes can be managed and treated. Controlling the blood pressure, Physiotheraphy taking care that the child is only one month old.

c) Every organ has its own metabolic profile and liver, the most potent organ of the body with regenerative capacity have the normal oxidative activity of the mitochondria of the liver compared to damaged muscle mitochondria. The early sysmptoms include the brain atrophy, low muscle tone i.e hypotonia suggesting that the coordination between the cells and delay in muscle development. Thus this might be the reason of damaged oxidative activity of muscle mitochondria.