Enzyme regulation allosteric control

A. Many metabolic pathways are regulated by allosteric control of key enzymes catalyzing the rate-limiting step of the pathway (Figure 5-1). 

Allosteric regulation can be considerably more complex. An example is the remarkable set of allosteric controls exerted on glutamine synthetase of E. coli (Fig. 22-6). Six products derived from glutamine serve as negative feedback modulators of the enzyme, and the overall effects of these and other modulators are more than additive. Such regulation is called concerted inhibition. 

Allosteric Regulation Allows an Enzyme to Be Controlled Rapidly by Materials that Are Structurally Unrelated to the Substrate... 

Allosteric control involves the reversible binding of a compound to an allosteric site referred to as a regulatory site on the enzyme. These compounds may be either one of the compounds involved in the metabolic pathway (feedback regulators) or a compound that is not a product of the metabolic pathway. In both cases, the binding usually results in conformational changes, which either activate or deactivate the enzyme. Proenzymes also act as a form of enzyme control. 

Thus, regulation of ADPGlc PPase, at both the transcriptional level and by allosteric control of the enzyme, modulates the rate of ADPglucose synthesis and starch synthesis. 

Organs serve as reservoirs or sites for synthesis of the metabolites required for homeostasis at all levels homeostasis is regulated by the endocrine system. Fluxes of metabolites through biochemical pathways are regulated by stoichiometric need, allosteric control of enzyme activity, modification of regulatory enzymes, and changes in their rate of enzyme synthesis or degradation. Hormones often influence these processes and, in turn, metabolites modulate the secretion of hormones. Thus, many... 

D-Fructose 1,6-diphosphatase is a regulatory enzyme playing a key role in the control of gluconeogenesis. A number of mechanisms have been proposed for the regulation of D-fructose 1,6-diphosphatase activity, including allosteric control by AMP,396 inhibition by D-fructose 1,6-bisphosphate, ADP, or ATP, and modification of the sulfhydryl groups of the enzyme.397,398... 

Attack points are metal ion centers and specific cysteine residues of proteins. The mechanisms by which cysteine nitrosylation regulates protein functions can be broadly described in allosteric terms similar to protein phosphorylation. Often, 02-mediated redox reactions cooperate in the allosteric control by NO of protein functions. S-nitrosylation of target proteins is a redox-based signal with exquisite specificity based on the selective modification of single cysteine residues. The selectivity of S-nitrosylation has been shown to be provided by both the subcellular distribution of NOS enzymes and the sequence context of cysteine residues in target proteins. Two nitrosylation motifs have been identified. In one motif, the target cysteine is located between an acidic and a basic amino acid, as revealed in either the primary sequence or the tertiary structure. In the other motif, the cysteine is contained in a hydrophobic region. 

The chemical reactions in living cells are organized into a series of biochemical pathways. The pathways are controlled primarily by adjusting the concentrations and activities of enzymes through genetic control, covalent modification, allosteric regulation, and compartmentation. 

A different control mechanism results from allosteric interactions between distinct sites this is a central regulatory mechanism employed by proteins. While there are numerous examples of allosteric control of the activity of enzymes, receptors, and transport proteins, regulation of ET in redox enzymes has rarely been documented, and no kinetic analysis of such processes has been performed. Interestingly, site-site interactions involved in control of electron... 

These enzymic reactions are essential to all living cells in that they provide the monomeric precursors for the de novo synthesis of DNA. The production of the 2 -deoxyribonucleoside phosphates required for DNA synthesis is carefully regulated through allosteric control of the enzyme by 2 -deoxynucleoside triphosphates and ATP, which regulate both overall activity and substrate specificity. 

We have seen how allosteric control can provide feedback regulation to maintain order in the body and respond to its needs. Allosteric control is reversible and the analogous type of regulation by covalent modification is the reversible modification of amino-acid side chains. Some enzymes are affected directly by both types of control. By far the most common modification of proteins is the phosphorylation of serine and threonine residues, and tyrosine phosphorylation is a key part of many control mechanisms. Protein phosphorylation is discussed below. Many other types of protein modification occursome reversible and some irreversible. 

The main differences between direct allosteric control of an enzyme (allosteric regulator interacts directly with the enzyme to be regulated) and control through covalent modification are ... 

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