Question

Describe the clinical consequences of a genetic or nutritional deficiency in the enzyme or cofactor listed below. Describe the cause of this disease (lack of type of food or genetic inheritance pattern) and its prevalence. Include any theory that describes the molecular mechanisms that connect the lack of enzyme activity to the disease symptoms.

a) hexokinase
b) phosphofructokinase
c) glyceraldehyde 3-phosphate kinase

Answer 1

a) hexokinase deficiency

hexokinase deficiency is usually caused due to a mutation in HK1 gene. it leads to hemolytic anaemia.

hexokinase is the major enzyme in glycolysis, where it catalyzes the first step, the conversion of glucose to glucose-6-phosphate.

the deficiency of this enzyme results in defective glycolysis. RBC mostly depends on glycolysis for energy. when glycolysis becomes defective, RBC cannot function properly and hemolysis occurs. when the RBC cannot replace the destroyed RBC, anaemia occurs.

it is an autosomal recessive disorder.

b) PFK deficiency

this deficiency leads to glycogen storage type VII disease or Tarui disease. PFK is also involved in glycolysis, where it phosphorylates fructose,6-phosphate to fructose,1,6-bisphosphate which is later cleaved into DHAP and glyceraldehyde,3-phosphate. due to the deficiency of this enzyme, the muscle would be unable to utilise glucose as its energy source. symptoms include muscle aches and cramps. it may also result in anaemia.

it is an autosomal recessive disorder.

c) G-3P kinase deficiency

glycerol kinase catalyzes the phosphorylation of glycerol to glycerol,3-phosphate, which plays a role in the synthesis of triacylglycerides and fat storage.

it is an X-linked recessive disorder.