Aldehyde dehydrogenase

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Image:1nzx.png
Crystal Structure of Aldehyde dehydrogenase, 1nzx

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

3D Structures of Aldehyde dehydrogenase

Updated on 12-April-2015

References

  1. Keller, Markus A.; Zander, Ulrich; Fuchs, Julian E.; Kreutz, Christoph; Watschinger, Katrin et al. (2014). A gatekeeper helix determines the substrate specificity of Sjögren–Larsson Syndrome enzyme fatty aldehyde dehydrogenase. Nature Communications vol. 5.

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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