Glyoxylate detoxification is an important function of the peroxisomes in humans cells, in particular hepatocytes. Glyoxylate is a highly reactive aldehyde which is generated in the intermediary metabolism of glycine, hydroxyproline and glycolate (Salido et al. 2012). The conversion of glycolate to glyoxylate is catalysed by the enzyme glycolate reductase.
Peroxisomes are ideal for glyoxylate detoxification due to the high abundance of the enzyme alanine glyoxylate aminotransferase (AGT) within the matrix. This enzyme is found to catalyse the transamination of glyoxylate to glycine, with the use of alanine as an amino-group donor (Wanders 2014). Glyoxylate can be transported to the peroxisome from the cytosol and mitochondria, and cross the peroxisome membrane through the channel-forming protein PXMP2 (Salido et al. 2012). Once glycine is formed, it is transported out into the cytosol where it is oxidised via the glycine cleavage pathway in the mitochondria (Wanders, 2014). A deficiency in AGT can result in the accumulation of glyoxylate, which can either be reduced to form glycolate - a water soluble compound that can be excreted out through the urine - or oxidised to oxalate by the enzyme lactate dehydrogenase. Oxalate usually precipitates as calcium oxalate, which has detrimental consequences (Wanders, 2014). These include renal failure and the formation of crystals, resulting in kidney stones (Guo and McMartin, 2005). |
Adapted from Danpure and Rumsby (2004)
|