Somatic Cell and Molecular Genetics, Vol. 25, No. 2, 1999, pp. 109-113 Brief Communication Radiation Hybrid Mapping of Human Cytosolic Malate Dehydrogenase (hcMDH) to the Short Arm of Chromosome 2 Agnes Shuk Yee Lo, Choong Tsek Liew,2 Patrick Tik Wan Law, Merce Garcia-Barcelo, Stephen Kwok Wing Tsui, Kwok Pui Fung, Cheuk Yu Lee, and Mary Miu Yee Waye1 1 Department of Biochemistry and The Hong Kong Bioinformatics Center, The Chinese University of Hong Kong, Hong Kong; 2Department of Anatomical and Cellular Pathology, The Prince of Wales Hospital Hong Kong Recieved 24 January 2000—Final 7 August 2000 Abstract—Compartmentalization of human cytosolic malate dehydrogenase, hcMDH, together with its isozyme partner-mitochondrial form, hmMDH, plays an important role in the aerobic metabolism of the malate-aspartate shuttle and the citric acid cycle. However, they share few structural homology at the molecular level. The pseudogenes of mMDH has been reported in mice but hcMDH has no pseudogenes as shown by Southern blot analysis. A single band only was detected for the EcoRI digestion with 9.4 kb long of human genomic DNA and HindIII cutting with 2.8kb long. hcMDH gene was mapped to chromosome 2 by somatic cell hybrid analysis and further localised to 268.72cR from the top telomere of Chromosome 2 (near 2p15) by radiation hybrid mapping. The genes falling into this region may be related to dilated cardiomyopathy (DCM), several types of cancers and immunoregulation mechanism of cancers. INTRODUCTION NAD+-dependent malate dehydrogenase (MDH) (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) catalyses the reversible conversion of L-malate to oxaloacetate by reduction of NAD+ to NADH (1). In mammals, two different isoen- zymes: cytosolic MDH (cMDH) and mitochon- drial MDH (mMDH) are distributed at different cellular compartments and play a crucial role in the malate shuttle and the citric acid cycle, respectively. They are encoded by nuclear genes and are synthesized in the cytoplasm (2). Cytosolic MDH remains in the cytosol after synthesis whereas mMDH is translocated into the mitochondrial matrix facilitated by the extra amino terminus leader polypeptide chain (3, 4). They show a very high similarity in three-di- mensional structure and structural organization at the protein level in Which the gene is divided into nucleotide-binding domain, catalytic do- main and carboxylation terminal tail (5, 6). However, they share a low identity of amino acid sequence with mammalian species (7-9). In contrast, mouse mMDH share about 52% with T. flavus MDH; whereas mouse cMDH shares about 56% with E. coli MDH, especially with higher homology in the subunit-subunit interface (10). Moreover, citrate synthase, an- other enzyme in the Kreb's cycle, has a very high homology between two eukaryotic isozymes but has a marked difference from the prokaryotic types. Southern blot hybridization 109 0740-7750/99/0300-0109$ 16.00/0 c 1999 Plenum Publishing Corporation