Metabolic control Covalent modification

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

This sort of control is usually achieved by either covalent modification (phosphorylation or de phosphorylation as in glycogen metabolism) or by proteolytic cleavage (e.g. activation of digestive enzymes in the gut, or blood clotting mechanism. 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

The flow of intermediates through metabolic pathways is controlled by 1bir mechanisms 1) the availability of substrates 2) allosteric activation and inhibition of enzymes 3) covalent modification of enzymes and 4) induction-repression of enzyme synthesis. This scheme may at first seem unnecessarily redundant however, each mechanism operates on a different timescale (Figure 24.1), and allows the body to adapt to a wde variety of physiologic situations. In the fed state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol, and protein. 

A Few Covalent Modification Reactions Utilized to Control Metabolism... 

Metabolic regulation 535 — 581 control elements of 536 sensitivity coefficient 537 Metabolism. See also Specific compounds activation 507, 508 beta oxidation 511, 512 control by covalent modification reactions table 543... 

Cells regulate their metabolic activities by controlling rates of enzyme synthesis and degradation and by adjusting the activities of specific enzymes. Enzyme activities vary in response to changes in pH, temperature, and the concentrations of substrates or products, but also can be controlled by covalent modifications of the protein or by interactions with activators or inhibitors. 

The most common way of regulating metabolic activity is by direct control of enzyme activity. Enzyme activities are usually regulated by noncovalent interaction with small-molecule regulatory factors (see chapter 9) or by a reversible covalent modification, such as phosphorylation or... 

Cohen, P., Control of Enzyme Activity, 2d ed. London and New York Chapman and Hall, 1983. Brief discussion of some types of regulation of activity of metabolic enzymes, emphasizing regulation by covalent modification of the enzymes. 

Enzyme activity can be regulated by covalent modification or by noncovalent (allosteric) modification. A few enzymes can undergo both forms of modification (e.g., glycogen phosphorylase and glutamine synthetase). Some covalent chemical modifications are phosphorylation and dephosphorylation, acetylation and deacetylation, adeny-lylation and deadenylylation, uridylylation and deuridyly-lation, and methylation and demethylation. In mammalian systems, phosphorylation and dephosphorylation are most commonly used as means of metabolic control. Phosphorylation is catalyzed by protein kinases and occurs at specific seryl (or threonyl) residues and occasionally at tyrosyl residues these amino acid residues are not usually part of the catalytic site of the enzyme. Dephosphorylation is accomplished by phosphoprotein phosphatases ... 

The reversible covalent modification of enzymes is important in control of metabolism, cell growth and division, response to hormones, and other processes. Examples of the types of reversible side-chain modifications found in cells include ... 

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