Identification and characterisation of the currently unknown gene for human carnosine synthetase (EC 6.3.2.11) upon purification of the homologous enzyme from Gallus gallus

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The currently unknown gene for human carnosine synthetase (EC 6.3.2.11) will be identified in order to facilitate studies on carnosine metabolism in the development of diabetic nephropathy. Furthermore, the physiological role of the dipeptide carnosine (β-alanyl-L-histidine), which is present in high concentrations (up to 20 mM) in human skeletal muscle, is still unclear. The biochemical characterization of the carnosine producing enzyme should contribute to the general understanding of carnosine function. We recently found that a variant of the carnosin-degrading enzyme serum carnosinase is associated with protection from diabetic nephrophathy. The biological basis of this effect is unclear. Carnosine synthetase has been purified earlier from Gallus gallus but sequence information was not produced. The enzyme was reported to be difficult to handle. With new chromatographic methods isolation of the protein should be straightforward. Following purification, sequence information will be generated and the homologous mammalian genes will be identified in silico. The expression level will be followed in various tissues. The relevance of possible functional variants of carnosine synthetase in the pathogenesis of diabetic nephropathy will be examined through association studies in patients and controls.