Related Experiment Video
Updated: Aug 17, 2026

Quantification of Coenzyme A in Cells and Tissues
Published on: September 27, 2019
Glutaconyl-CoA is the main toxic agent in glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)
Willy Lehnert1, Jörn Oliver Sass
1Stoffwechsellabor, Zentrum für Kinderheilkunde- und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstr. 1, D-79106 Freiburg, Germany.
Abstract:
Despite early diagnosis and treatment, 35% of the patients with glutaric aciduria type I (GA I) develop severe neurologic damage. Glutaric acid and 3-hydroxyglutaric acid have been suspected to cause neurodegeneration. Lately, this has been questioned, however. We postulate that glutaconyl Coenzyme A (glutaconyl-CoA) is responsible for brain damage. Chemically, glutaconyl-CoA is an analogue of acrylyl-CoA, the parent substance of the extremely reactive class of acrylates. It is expected to react spontaneously with sulfhydryl groups, thus modifying membranes, disturbing enzyme functions and trapping glutathione. Enhanced production of glutaconyl-CoA together with lack of glutathione precipitates brain damage. Such a mechanism is supported by three findings. (1) The addition product of glutaconyl-CoA to cysteine is present in small amounts in normal human urine. (2) Reaction of methacrylyl-CoA with free sulfhydryl groups has been reported previously in a patient with 3-hydroxyisobutyryl CoA deacylase deficiency. (3) Glutathione has been found to be decreased in homozygous glutaryl-CoA dehydrogenase-deficient knock-out mice.
More Related Videos
Related Concept Videos
Inborn Errors of Metabolism
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Amino Acid Biosynthetic Pathways
Hepatic Encephalopathy

