Epigenetic formation of lactate dehydrogenase isozymes in the house mouse, Mus musculus.
The origin of mouse lactate dehydrogenase (LDH) sub-bands was investigated by using our miniaturized polyacrylamide gel electrophoretic apparatus. Mouse LDH isozymes are generated by combinations of three types of A subunit, the primary type and two epigenetically modified forms. These are designated A1, A2, and A3 in the order of their electrophoretic mobilities towards the anode. The A1 subunit arises from the covalent binding of molecules of glutathione through disulfide bonds to the original subunit, A3. The A2 subunit arises from the covalent binding of molecules of cysteine through disulfide bonds to the A3 subunit. All isozymes can be explained as tetramers composed of the three kinds of A subunit (A1, A2, or A3) in combination with B subunits to yield a total of 35 isozymes. The kinetic properties of these sub-bands were also examined. There was no difference between A24 and A34 in the Km for pyruvate and for lactate. Thermostability at 56 degrees C was greater for A34 than for A24. The activities of tetramers at the electrophoretic position of A3B1 and A4 in extracts containing all five isozymes were increased by treatment of the extracts with high concentrations of reduced glutathione or cysteine with the concomitant disappearance or decrease in activity of tetramers at the position of B4 and A3B1. These results suggest that, in the presence of reduced glutathione or cysteine, LDH isozymes containing the B subunit are first dissociated and then the A subunits are preferentaially recombined.
D000818:Animals; D001921:Brain / Q000201:enzymology; D003964:Diaphragm / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism*; D005123:Eye / Q000201:enzymology; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis*; D008297:Male; D051379:Mice / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D012469:Salivary Glands / Q000201:enzymology; D013737:Testis / Q000201:enzymology
D004792:Enzyme Precursors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase