3-Hydroxy-3-methylglutaryl-CoA lyase

[4] Electron density was observed indicating a bound metal ion, presumably Mg2+ due to its inclusion in the crystallization medium.

The substrate binding site includes arginine 41 making a salt bridge to the carboxylate of the hydroxyglutaric acid closest to metal ion.

[5] The enzyme is required for ketogenesis in the liver, and is also responsible for processing the amino acid leucine inside the mitochondrion Deficiency HMG-CoA lyase deficiency causes hypoketotic hypoglycemia similar to that is caused by HMGCS2 mutations but also leads to organic acid accumulation and metabolic acidosis due to altered leucine metabolism.

Mutations in the HMGCL gene cause 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD), a rare autosomal recessive inborn error of metabolism characterized by disruption of ketogenesis and L-leucine catabolism.

Clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia, and lethargy.

Substrate binding site makes a salt bridge between the 3HG (3-Hydroxy-3-methylglutaryl-CoA lyase) substrate and active Arg 41 with bond distance of 3.3Å. Also displays the bond between Arg 41 and Glu72 holding the structure in place. PDB code: 2cw6
Metal-Ligand binding site displays octahedral bonding coordination utilizing 4 amino acids and 2 water molecules all with distances within 2.2Å . PDB code: 2cw6
Ketogenesis