Enzymes glycolytic

Thus a key role has been proposed for phosphoenolpyruvate in regulating glycolysis, in general, acting as an efficient carbon source and providing ATP (Plaxton et al., 1993). Nonetheless, the most effective compound so far determined is L-malate which can arise from pyruvate metabolism (Smith et al., 1992). 

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The most frequent of the domain structures are the alpha/beta (a/P) domains, which consist of a central parallel or mixed P sheet surrounded by a helices. All the glycolytic enzymes are a/p structures as are many other enzymes as well as proteins that bind and transport metabolites. In a/p domains, binding crevices are formed by loop regions. These regions do not contribute to the structural stability of the fold but participate in binding and catalytic action. 

For example, each subunit of the dimeric glycolytic enzyme triosephos-phate isomerase (see Figure 4.1a) consists of one such barrel domain. The polypeptide chain has 248 residues in which the first p strand of the barrel starts at residue 6 and the last a helix of the barrel ends at residue 246. In contrast, the subunit of the glycolytic enzyme pyruvate kinase (Figure 4.5), which was solved at 2.6 A resolution in the laboratory of Ffilary Muirhead, Bristol University, UK, is folded into four different domains. The polypeptide chain of this cat muscle enzyme has 530 residues. In Figure 4.5, residues 1-42... 

ATP 2 ADR The structure was determined to 3.0 A resolution in the laboratory of Georg Schulz in Heidelberg, Germany, (c) The ATP-binding domain of the glycolytic enzyme hexokinase, which catalyzes the phosphorylation of glucose. 

The stmcture was determined to 2.8 A resolution in the laboratory of Tom Steitz, Yale University, (d) The glycolytic enzyme phospho-glycerate mutase, which catalyzes transfer of a phos-phoryl group from carbon 3 to carbon 2 In phosphoglycerate. The structure was determined to 2.S A resolution in the laboratory of Herman Watson, Bristol University, UK. (Adapted from J. Richardson.)... 

Sternberg, M.J.E., et al. Analysis and prediction of structural motifs in the glycolytic enzymes. Phil. Trans. 

Thus far, we have considered enzyme-catalyzed reactions involving one or two substrates. How are the kinetics described in those cases in which more than two substrates participate in the reaction An example might be the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (Chapter 19) ... 

Vertessy, B. G., Orosz, F., Kovacs, J., and Ovadi, J., 1997. Alternative binding of two sequential glycolytic enzymes to microtnbnles. Molecnlar studies in the phosphofrnctokinase/aldolase/microtnbnle Journal of... 

Melarsoprol, a trivalent organic melaminophenyl arsenic compound, kills intracerebral parasites of both T. brucei gambiense and T. brucei rhodesiense. Melarsoprol accumulates via an adenosine/adenine transporter in trypanosomes and is believed to inhibit glycolytic enzymes. Melarsoprol leads to a rapid lysis of trypanosomes. Melarsoprol is highly toxic to humans. 

A three-dimensional meshwork of proteinaceous filaments of various sizes fills the space between the organelles of all eukaryotic cell types. This material is known collectively as the cytoskeleton, but despite the static property implied by this name, the cytoskeleton is plastic and dynamic. Not only must the cytoplasm move and modify its shape when a cell changes its position or shape, but the cytoskeleton itself causes these movements. In addition to motility, the cytoskeleton plays a role in metabolism. Several glycolytic enzymes are known to be associated with actin filaments, possibly to concentrate substrate and enzymes locally. Many mRNA species appear to be bound by filaments, especially in egg cells where they may be immobilized in distinct regions thereby becoming concentrated in defined tissues upon subsequent cell divisions. 

A decreased glycolytic rate has been proposed as a cause of muscle fatigue and related to pH inhibition of glycolytic enzymes. Decreasing pH inhibits both phosphorylase kinase and phosphofructokinase (PFK) activities. PFK is rate determining for glycolytic flux and therefore must be precisely matched to the rate of ATP expenditure. The essential characteristic of PFK control is allosteric inhibition by ATP. This inhibition is increased by H and PCr (Storey and Hochachka, 1974 ... 

Triose phosphate isomerase (TPI) catalyzes the interconversion of glyceralde-hyde-3-phosphate and dihydoxyacetone phosphate and has an important role in glycolysis, gluconeogenesis, fatty acid synthesis, and the hexose monophosphate pathway. Red blood cell TPI activity measured in vitro is approximately 1000 times that of Hx, the least active glycolytic enzyme. TPI is a dimer of identical subunits, each of molecular weight 27,000, and does not utilize cofactors or metal ions. Posttranslational modification of one or both subunits may occur by deamidination, resulting in multiple forms of the enzymes and creating a complex multibanded pattern on electrophoresis. 

VI. Valentine, W. N Tanaka, K. R., and Miwa, S A specific erythrocyte glycolytic enzyme defect (pyruvate kinase) in three subjects with congenital non-spherocytic hemolytic anemia. Trans. Assoc. Am. Physicians 74, 100-110 (1961). 

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

Paul I wanted to come back to the issue of mitochondria and Ca2+. I happen to have friends on both sides of that issue. We have been promoting the idea, which seems to work in a variety of tissues, that subsarcolemmal space is highly populated by glycolytic enzymes. This is true in skeletal muscles also. One of the first things seen with ouabain is that it kills the lactate production without touching oxygen... 

Genetically-determined deficiency of G6PD is the most common cause of haemolysis arising from enzyme defects. Mutated glycolytic enzymes such as hexokinase, phosphofructokinase, aldolase and pyruvate kinase can also bring about haemolysis but the occurrence of these defects are much rarer than for G6PD deficiency (see Case N otes at the end of this chapter). 

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