Triosephosphate isomerase metabolism

Citrate synthase catalyzes the metabolically important formation of citrate from ace-tyl-CoA and oxaloacetate [68]. Asp-375 (numbering for pig CS) has been shown to be the base for the rate-limiting deprotonation of acetyl-CoA (Fig. 5) [69]. An intennediate (which subsequently attacks the second substrate, oxaloacetate) is believed to be formed in this step the intermediate is thought to be stabilized by a hydrogen bond with His-274. It is uncertain from the experimental data whether this intermediate is the enolate or enol of acetyl-CoA related questions arise in several similar enzymatic reactions such as that catalyzed by triosephosphate isomerase. From the relative pK values of Asp-375... 

S., Ovadi, J. Triosephosphate isomerase deficiency consequences of an inherited mutation at mRNA, protein and metabolic levels. Biochem. J. 2005, 392 675-683. 

Dihydroxyacetone phosphate is converted to D-glyceraldehyde 3-phosphate by the enzyme triosephosphate isomerase as part of the glycolytic pathway of metabolism. Show how this interconversion could occur by a base-catalyzed mechanism ... 

Repiso A, Boren J, Ortega F, Pujades A, CenteHes J, Vives-Corrons JL, et al. Triosephosphate isomerase deficiency, genetic, enzymatic and metabolic chai ac-terization of a new case from Spain. Haematologica 2002 87 ECR12. 

A number of studies on the metabolism of 3FG and 4FG in Locusta miaratoria have been undertaken. Both 3FG and 4FG are toxic to locust with LD50 s of 4.8 mg/g and 0.6 mg/g respectively. In vitro studies showed that 3FG is metabolized in the fat body, via the NADP-linked aldose reductase, to 3-deoxy-3-fluoro-D-glucitol (3FGL). This metabolite was detected in the hemolymph of the insect and shown to be both a competitive inhibitor and a substrate for NAD-linked sorbitol dehydrogenase, thereby generating 3-deoxy-3-fluoro-D-fructose (3FF) (541. Subsequently, it was shown by in vivo radio-respirometric analysis of C02 and appropriate chase experiments, that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate shunt or tricarboxylic acid cycle (55). In addition, the release of fluoride ion and H20 from D-[3- H]-3FG was also observed. Based on the mechanism of aldolase (55) and triosephosphate isomerase... 

Figure 11.1 Proposed pathway for hex-ose metabolism of homofermentative LAB (1) and (2) phosphoenolpyruvate (PEP)-dependent sugar phosphotransferase system (PTS) (3) mannitol-specific PTS (4) phospho-glucose isomerase (5) mannitol-1-phosphate dehydrogenase (6) mannitol-1-phosphatase (7) 6-phosphofructokinase (8) fructose-diphosphatase (9) fructose-1,6-diphosphate aldolase (10) triosephosphate isomerase (11) glyceraldehyde-3-phosphate dehydrogenase...

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