Trimethyllysine dioxygenase, mitochondrial is an enzyme that in humans is encoded by the TMLHEgene in chromosome X. Mutations in the TMLHE gene resulting in carnitine biosynthesis disruption have been associated with autism symptoms.
Structure
The TMHLE gene is located at the extreme end of the Xq28 region with high genomic instability, and encodes a protein trimethyllysine dioxygenase, a, Fe2+ and 2-oxoglytarate dependent non-heme-ferrous iron hydrolase localized to the mitochondrial matrix.
Function
The trimethyllysine dioxygenase enzyme catalyzes the first step in the carnitine biosynthesis pathway, which is part of amine biosynthesis. Carnitine is a molecule that play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane where they are metabolized. The encoded protein converts trimethyllysine into hydroxytrimethyllysine with the reaction (EC 1.14.11.8):
N6,N6,N(6)-trimethyl-L-lysine + 2-oxoglutarate + O2 = 3-hydroxy-N6,N6,N(6)-trimethyl-L-lysine + succinate + CO2 and requires iron and L-ascorbate as co-factors.
12Ziats MN, Comeaux MS, Yang Y, Scaglia F, Elsea SH, Sun Q, etal. (September 2015). "Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation". American Journal of Medical Genetics. Part a. 167A (9): 2162–2167. doi:10.1002/ajmg.a.37144. PMID25943046. S2CID205320608.
↑Monfregola J, Napolitano G, Conte I, Cevenini A, Migliaccio C, D'Urso M, etal. (2007). "Functional characterization of the TMLH gene: promoter analysis, in situ hybridization, identification and mapping of alternative splicing variants". Gene. 395 (1–2): 86–97. doi:10.1016/j.gene.2007.02.012. PMID17408883.
12Monfregola J, Cevenini A, Terracciano A, van Vlies N, Arbucci S, Wanders RJ, etal. (2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting". Journal of Cellular Physiology. 204 (3): 839–847. doi:10.1002/jcp.20332. PMID15754339. S2CID25224767.
