Glyoxylate reductase

Glyoxylate reductase (EC 1.1.1.26), first isolated from spinach leaves, is an enzyme that catalyzes the reduction of glyoxylate to glycolate, using the cofactor NADH or NADPH. Glyoxylate reductase (EC 1.1.1.26), first isolated from spinach leaves, is an enzyme that catalyzes the reduction of glyoxylate to glycolate, using the cofactor NADH or NADPH. The systematic name of this enzyme class is glycolate:NAD+ oxidoreductase. Other names in common use include NADH-glyoxylate reductase, glyoxylic acid reductase, and NADH-dependent glyoxylate reductase. The crystal structure of the glyoxylate reductase enzyme from the hyperthermophilic archeon Pyrococcus horiskoshii OT3 has been reported. The enzyme exists in the dimeric form. Each monomer has two domains: a substrate-binding domain where glyoxylate binds, and a nucleotide-binding domain where the NAD(P)H cofactor binds. The enzyme catalyzes the transfer of a hydride from NAD(P)H to glyoxylate, causing a reduction of the substrate to glycolate and an oxidation of the cofactor to NAD(P)+. Figure 2 shows the mechanism for this reaction. It is thought that the two residues Glu270 and His288 are important for the enzyme's catalytic function, while the residue Arg241 is thought to be important for substrate specificity. The glyoxylate reductase enzyme localizes to the cell cytoplasm in plants. It can use both NADPH and NADH as a cofactor, but prefers NADPH. The enzyme substrate, glyoxylate, is a metabolite in plant photorespiration, and is produced in the peroxisome. Glyoxylate is important in the plant cell as it can deactivate RUBISCO and inhibit its activation. Hence, glyoxylate levels are important in regulating photosynthesis. The enzyme is thought of as a glyoxylate-glycolate shuttle that helps in the disposal of excess reducing equivalents from photosynthesis. This is supported by the following findings: (1) glycolate biosynthesis in the chloroplasts is highest at low CO2 concentrations, (2) the enzyme is quite specific for the NADPH cofactor which is a final product of electron transfer in the chloroplasts during photosynthesis, and (3) when isolated chloroplasts are exposed to light, they absorb glyoxylate and reduce it, but they do not absorb glycolate. Due to the link between glyoxylate levels and photosynthesis, an increase in glyoxylate levels indicates that the plant is under stress. As glyoxylate levels continue to increase, they can harm the plant by (1) reacting with DNA, (2) oxidizing membrane lipids, (3) modifying proteins, and (4) increasing the transcription of stress-related genes in the plant. This highlights the importance of glyoxylate reductase, as it helps keep plant cells healthy and detoxifies the cell by reducing glyoxylate levels. In the absence of the enzyme, the side-effects of increased glyoxylate activity can cause cellular and developmental problems in the plant. Glyoxylate reductase can be used as a tool for studying photorespiratory carbon metabolism in plant leaves. Such studies can be carried out using acetohydroxamate and aminooxyacetate, which have been found to inhibit glyoxylate reductase activity. These inhibitors are not fully specific, but provide fully reversible inhibition of the enzyme and so provide a flexible tool for metabolic studies in plants.