Lactate dehydrogenase catalytic cycle

Proton transfers are particularly common. This acid-base catalysis by enzymes is much more effective than the exchange of protons between acids and bases in solution. In many cases, chemical groups are temporarily bound covalently to the amino acid residues of the enzyme or to coenzymes during the catalytic cycle. This effect is referred to as covalent catalysis (see the transaminases, for example p. 178). The principles of enzyme catalysis sketched out here are discussed in greater detail on p. 100 using the example of lactate dehydrogenase. 

The active center of an LDH subunit is shown schematically in Fig. 2. The peptide backbone is shown as a light blue tube. Also shown are the substrate lactate (red), the coenzyme NAD (yellow), and three amino acid side chains (Arg-109, Arg-171, and His-195 green), which are directly involved in the catalysis. A peptide loop (pink) formed by amino acid residues 98-111 is also shown. In the absence of substrate and coenzyme, this partial structure is open and allows access to the substrate binding site (not shown). In the enzyme lactate NAD"" complex shown, the peptide loop closes the active center. The catalytic cycle of lactate dehydrogenase is discussed on the next page. 

From all the hypotheses mentioned above, the low flux of pyruvate into the TCA cycle is better explained by a decreased activity of several enzymes pyruvate carboxylase, pyruvate phosphoenol carboxykinase, pyruvate dehydrogenase, and malic enzyme II (Figure 4.3). Then, the pyruvate accumulated is converted to lactate by the enhanced catalytic action of the lactate dehydrogenase, as an alternative pathway to generate energy for cellular processes. 

Clarke, A. R., Waldman, A. D. B., Hart, K. W., Holbrook, J. J. (1985) The Rates of Defined Changes in Protein Structure During the Catalytic Cycle of Lactate Dehydrogenase, Biochim. Biophys. Acta S29, 397-407. 

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