Dihydropicolinate

Fig. 2. Three-dimensional structure of M. tuberculosis dihydropicolinate reductase consisting of the Rossmann-fold domain with bound NAD (stick representation and the catalytic domain with bound the substrate pyridine-2,6-dicarboxylic acid (stick representation (100).

S cystathionine y-synthase cystathionine /3-lyase methionine synthase ) dihydropicolinate synthase... 

Seven enzyme catalyzed reactions are required for the synthesis of lysine from pyruvate and aspartate semialdehyde as illustrated in Fig. 3. However, enzymes catalyzing only the first and last of these reactions have been isolated from plants. Dihydropicolinate synthase facilitates the condensation of the precursors during a reaction which presumably proceeds in two steps. A double bond between the C-4 of the semialdehyde and the methyl carbon of pyruvate would be formed, with the loss of water, followed by spontaneous ring closure and the loss of a second molecule of water. Catalysis of this reaction in plant extracts was first demonstrated by Cheshire and Miflin (1975) using maize seedlings as the source of the enzyme. Mazelis et al. (1977) detected the enzyme in extracts obtained from six different taxonomic families of plants and partially purified the enzyme from wheat germ. Only the L isomer of aspartate semialdehyde was active as a substrate of this enzyme and strong cooperativity was noted when the concentration of pyruvate was varied. A dihydropicolinate synthase has also been isolated from carrot cells (Matthews and Widholm, 1978). 

Enzymes which could catalyze the next four reactions in the pathway have not been isolated from plants. Assuming that these reactions are analogous to those which occur in microorganisms, the NAD(P)H-dependent reduction of 2,3-dihydropicolinate to A -piperidine-2,6-dicarboxylate would be followed by acylation of the amino group (the latter reaction may involve prior nonen-zymatic hydrolysis of the C-N double bond). Acylation serves to protect the 2-amino group during the synthesis of the diamino intermediate either acetyl-CoA or succinyl-CoA is utilized in microorganisms. Deacylation of A -acyl-2,6-diaminopimelate results in the formation of a symmetrical l,l... 

The sequences of biochemical transformations involved in the synthesis of the aspartate family and branched-chain amino acids in multicellular plants are similar to those that occur in microorganisms. Support for this conclusion has been derived principally from isolation of a number of the requisite enzymes. Information on the kinetic and physical properties of enzymes is best achieved after extensive purification. In contrast, useful predictions of the physiological function of regulatory enzymes depend upon effective enzyme extraction and complete preservation of native properties. Since the latter objective has been emphasized during most investigations of enzymes associated with amino acid biosynthesis in plants, the bulk of our knowledge has been obtained from comparatively crude enzyme preparations. Results of both direct and competitive labeling experiments have added demonstrations of many of the predicted precursor-product relationships and a few metabolic intermediates have been isolated from plants. The nature of a number of intermediate reactions does, however, remain to be clarified notably, the reactions associated with the conversion of dihydropicolinate to lysine and those involved in the synthesis of leucine from 2-oxoisovalerate. 

In the case of dipicolinic acid, the biosynthetic pathway involves the formation of 2,3-dihydropicolinic acid which is an intermediate in lysine synthesis. See Pig. 2. (13)... 

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