Aldehyde dehydrogenase

Function

Aldehyde dehydrogenase (ALDH) converts aldehydes to carboxylic acids while reducing NAD+ to NADH. In mammals there are 3 classes of ALDH and each contain constitutive and inducible forms.

• ALDH class 1 is cytosolic.
  
• ALDH class 2 is mitochondrial.
  
• ALDH class 3 is found in tumors, stomach and cornea. ALDH3A1 is soluble and has substrate specificity to bulky aromatic aldehydes. ALDH3A2 is a fatty ALDH (FALDH). FALDH was found to have an additional gatekeeper helix at the substrate funnel entrance that is shaping the enzymes substrate specificity. ^[1]
  
• ALDH family 7 member A1 is known as antiquitin and functions in the detoxification of aldehydes.
  
• Glyceraldehyde-3-phophate (G3P)-ALDH is called GAPDH. GADPH catalyzes the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate in the presence of inorganic phosphate (Pi) and NAD. The aldehyde of G3P reacts with the cysteine-thiol to form a carboxylic acid in a high energy thioester form. The thioester is attacked by the inorganic phosphate and forms the acyl phosphate. GAPDH is part of the glycolysis pathway. GAPDH contains NAD-dependent and NADPH-dependent enzymes.

Disease

ALDH inhibition is associate with Parkinson disease. Inhibitors can include pesticides. Mitochondrial ALDH2 deficiency causes accumulation of acetaldehyde in the blood following alcohol consumption resulting in the syndrome known as Alcohol flush syndrome.

Relevance

Buildup of toxic aldehydes causes cell damage and cardiac diseases.

Structural highlights

A cysteine-thiol at the active site of GAPDH plays a role in catalysis.

• . Water molecules shown as red spheres.
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