Metabolic enzymes enolases

Many enzymes are dependent on dissociable metal ions for their activity, and the operation of most of the important metabolic systems thus requires the presence of these cofactors. For example, the list of enzymes requiring Mg is a long one and includes the oxidases and decarboxylases for the keto acids, most of the enzymes involved in phosphate metabolism, some dehydrogenases, some peptidases, phosphoglucomutase and enolase. These enzymes may be inhibited with inhibitors forming stable complexes with Mg ions. For example, malonate and other dicarboxylic compounds are able to chelate effectively with Mg" and other metal ions, and their inhibition may result from the reduction of metal ion concentration in the medium or the removal of the metal ions from the enzyme [3] ... 

Hydroxycyclopropanecarboxylic acid phosphate HCP 34 is an analogue of phosphoenolpyruvate (PEP) 35 which is metabolized by various enzymes. HCP 34 is a potent competitive inhibitor of enzymes utilizing PEP 35, such as PEP carboxylase, enolase, pyruvate kinase, and probably other enzymes. It is a substantially better inhibitor than phospholactate 36 or phosphoglycolate 37, presumably because of the similarity of its geometric and electronic structures with phosphoenol pyruvate,Eq. 12 [28]. 

Mode of Action. The fluoride ion inhibits enzymes, such as enolase, which require Mg as a prosthetic group, by precipitating a complex magnesium fluorophosphate thus it prevents phosphate transfer in oxidative metabolism. 

PEP is converted to fructose 1,6-bisphosphate in a series of steps that are a direct reversal of those in glycolysis (see Topic J3), using the enzymes enolase, phosphoglycerate mutase, phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, triose phosphate isomerase and aldolase (see Fig 1). This sequence of reactions uses one ATP and one NADH for each PEP molecule metabolized. 

Many metabolic processes such as glycolysis, Krebs cycle reactions, photosynthesis, protein synthesis, and lipid metabolism are affected by exposure to F. Much of the action of F on these processes can be attributed to F-dependent inhibition of enzymes. Examples of enzymes shown to be inhibited by F include enolase, phosphoglucomutase, phosphatase, hexokinase, PEP carboxylase, pyruvate kinase, succinic dehydrogenase, malic dehydrogenase, pyrophosphatase, phytase, nitrate reductase, mitochondrial ATPase, urease (Miller et al. 1983), lipase (Yu et al. 1987), amylase (Yu et al. 1988), invertase (Yu 1996 Ouchi et al. 1999), and superoxide dismutase (SOD) (Wilde and Yu 1998). 

In this step the enzyme enolase catalyzes the dehydration (removal of a water molecule) of 2-phosphoglycerate. The energy-rich product is phosphoenolpyruvate, the highest energy phosphorylated compound in metabolism. 

Fig. 1. Metabolic roles of lactate dehydrogenase. Other enzymes referred to are GAPDH (glyceraldehyde-3-phosphate dehydrogenase), PGK (phosphoglycerate kinase), PGM (phosphoglycerate mutase), PK (pyruvate kinase), and ENOL (enolase).

The reaction is pulled to the right by further metabolism of 2-phosphoglycerate. First, the compound is dehydrated by the removal of the hydroxyl group on carbon 3 and a proton from carbon 2, leaving a double bond between carbons 2 and 3. The enzyme responsible for this step is a lyase, enolase ... 

Fig. 15.2 Pyruvate metabolism, gluconeogenesis and glycolysis. Key enzymes shown are 1, fructose 1-phosphate aldolase (EC 4.1.2.13) 2, fructose 1,6-bisphosphate aldolase (EC 4.1.2.13) 3, NAD rglyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) 4, 3-phosphoglycerate kinase (EC 2.T.2.3) 5, phosphoglyceromutase (EC 2.7.5.3) 6, phosphopyruvate hydratase (enolase) (EC 4.2.1.11) 7, pyruvate kinase (EC 2.7.1.40) 8, pyruvate carboxylase (EC 6.4.1.1) 9, phosphopyruvate carboxylase...

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