MDH1

MDH1 or Malate Dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene. It is a key enzyme in the citric acid cycle or Krebs cycle, which is a central metabolic pathway in all aerobic organisms.

Function

MDH1 is a cytosolic NAD-dependent malate dehydrogenase that catalyzes the reversible oxidation of malate to oxaloacetate, using the coenzyme NAD/NADH. This reaction is part of many metabolic processes, including the citric acid cycle, gluconeogenesis, and the malate-aspartate shuttle.

Structure

The MDH1 gene is located on the short (p) arm of chromosome 2 at position 13.3. The protein encoded by this gene is a homodimer that consists of two identical subunits. Each subunit is composed of several domains, including a NAD-binding domain and a catalytic domain.

Clinical significance

Mutations in the MDH1 gene have been associated with various diseases, including cancer, diabetes, and neurodegenerative diseases. In cancer, overexpression of MDH1 has been observed in several types of tumors, suggesting a role in tumor growth and progression. In diabetes, alterations in MDH1 activity have been linked to insulin resistance and impaired glucose metabolism. In neurodegenerative diseases, decreased MDH1 activity has been implicated in neuronal death and dysfunction.

See also

• Malate dehydrogenase
• Citric acid cycle
• Coenzyme