Aldehyde Dehydrogenase Zach Lawton 1

Background Superfamily of Nictonamide adenine dinucleotide phosphate (NADP) enzymes Location: all three domains of life  Three subclasses of enzymes in eukaryotes  Cytosol, mitochondria, endoplasmic reticulum and cornea Function: catalyze aldehyde to carboxylic acid Importance:  Metabolism  Removal of toxic aldehydes  UV damage to the cornea  Hangovers 2

Amino Acid Sequence Alignment 3 Glu 268 Lys 192 Cys 302

Structure—ALDH2 Expressed as tetramer or octamer in most cases. Mitochondria ALDH2 shown. Percentage of alpha helix and beta sheets vary between each protein and class of ALDH. ALDH1 ALDH2  ~40% α-helix, ~35% β-sheet ALDH3  ~35% α-helix, ~5% β-sheet 4 Alpha Helix – Yellow Beta Sheet – Blue PDB = 1O05

Active Site—ALDH1 and ALDH2 NAD(P) + binds into the pocket where it is stabilized by Lys192. Interactions with Cys302 and Glu268. Mg 2+ is used as a catalysis. 5 Miller, S.J., Hurley, T.D. (2003) Coenzyme Isomerization is Intergral to Catalysis in Aldehyde. ACS Biochemistry. 42,

Reaction Mechanism 6

Conclusion ALDH is a NAD/P + Enzyme superfamily. Primary function: Converts aldehyde to carboxylic acid using Cystine and Glutamate residues. Three Subclasses  ALDH1  Cytosol  ALDH2  Mitochondria, Endoplasmic reticulum  ALDH3  Cornea and Liver QUESTIONS? 7