Distribution and properties of NADPH-linked aldehyde reductases from rat brain synaptosomes

Studies on the subcellular distribution of NADPH-linked aldehyde reductase from rat brain showed that 10% of the total reductase activity is located in the mitochondrial-synaptosomal fraction. There are differences in the percentages of reductase activity found in the synaptosomes compared to cytosol in various regions of the brain. The NADPH-linked aldehyde reductase from the synaptosomal fraction exhibited a nonlinear Lineweaver-Burk plot. This nonlinearity is due to the presence of two distinct aldehyde reductases, which can be distinguished by Michealis constants forp-nitrobenzaldehyde of 4.1×10(-5) M and 2.6×10(-6) M. The two NADPH-linked aldehyde reductases isolated from synaptosomes were further characterized according to pH optima, andK i values for inhibition by barbiturates. In addition regional distributions for the two enzymes were determined. TheK i values for pentobarbital for the "highK m " enzyme and the "lowK m " enzyme were estimated to be 2×10(-5) M and 6×10(-5) M, respectively. It was concluded from the above studies that the lowK m reductase is probably responsible for 3,4-dihydroxyphenylglycoaldehyde (derived from norepinephrine) reduction in brain and a role of the highK m enzyme for protection of neurons from high concentrations of chemically reactive aldehydes was proposed.