Human mutations in a gene encoding the DHTKD1 protein result in a range of neurological disturbances. On molecular level, the mutations cause accumulation of the reactive oxygen species (ROS) and degradation products of lysine and tryptophan, said the study published recently in the journal Free Radical Biology and Medicine.
The structure of the DHTKD1 protein is similar to an enzyme, 2-oxoglutarate dehydrogenase, which is able to produce superoxide.
According to the researcher, a cell combats the “poisonous” forms of oxygen with a help of antioxidants, and antioxidant defence system proteins.
But disturbed metabolism may cause a shortage of amino acids (the bricks for building proteins) lysine and tryptophan which may result into physical, neurologic and mental malfunctions, and even lead to death.
Those amino acids belong to irreplaceable and cannot be produced from other substances in human body, so they should come from food, the researchers noted.
According to the study, 2-aminoadipate and 2-oxoadipate are the degradation products of lysine, tryptophan and hydroxylysine.
Scientists found the connection between aciduria (increased acidity of urine, showing serious malfunction in metabolism) in patients with increased content of 2-aminoadipate and 2-oxoadipate and gene mutations in the DHTKD1 protein.
That confirmed an earlier hypothesis that an enzyme, encoded by DHTKD1, oxidises 2-oxoadipate.