3-Hydroxymethyl-3-Methylglutaryl Coenzyme A Lyase (HMGCL)

3-Hydroxy-3-methylglutaryl coenzyme A lyase is a homodimeric mitochondrial matrix enzyme that catalyzes the cleavage of HMG-CoA to acetoacetic acid and acetyl-CoA, the last step of both ketogenesis and leucine catabolism. A shortage of glucose-sparing ketone bodies normally produced during fasting was thought to be responsible for the hypoglycemia which characterizes this metabolic defect. The absence of ketonuria in this disorder is a direct consequence of the metabolic lesion. HMG-CoA lyase is involved in ketogenesis, and the patient with the deficiency is compromised in the ability to generate ketone bodies. Both parents had reduced levels of HMG-CoA lyase in leukocytes. Clinically, deficiency of the enzyme results in metabolic acidosis and hypoglycemia.