Enzyme regulation zymogens

Specialized controls Enzyme regulation is an important matter to cells, and evolution has provided a variety of additional options, including zymogens, isozymes, and modulator proteins. 

We turn now to a different mechanism of enzyme regulation. Many enzymes acquire full enzymatic activity as they spontaneously fold into their characteristic three-dimensional forms. In contrast, other enzymes are synthesized as inactive precursors that are subsequently activated by cleavage of one or a few specific peptide bonds. The inactive precursor is called a zymogen (or a proenzyme). A energy source (ATP) is not needed for cleavage. Therefore, in contrast with reversible regulation by phosphorylation, even proteins located outside cells can be activated by this means. 

Zymogen (e.g., trypsinogen and chymotrypsinogen) synthesis, secretion, transport, and activation and the rate of inactivation of the active enzyme by inhibitors may all be considered means of enzyme regulation. 

The enzymatic activity of these potentially harmful enzymes is tightly controlled. Once transcribed into protein, MMPs are expressed as inactive zymogens and require distinct activation processes to convert them into active enzymes. After secretion, MMP-activity is regulated by the noncovalent binding of tissue inhibitors of metalloproteinases ( TIMPs) as shown in Fig. 2 for MMP-2 and TIMP-2. Four TIMPs have been identified so far TIMP-1, TIMP-2, TIMP-3, and TIMP-4. All known MMPs can be inhibited by at least one of the four known TIMPs. Nevertheless, individual differences with regard to bond strength and thus the magnitude of inhibition of a particular MMP do exist. 

For some enzymes, an inactive precursor called a zymogen is cleaved to form the active enzyme. Many proteolytic enzymes (proteases) of the stomach and pancreas are regulated in this way. Chymotrypsin and trypsin are initially synthesized as chymotrypsinogen and trypsinogen (Fig. 6-33). Specific cleavage causes conformational changes that expose the enzyme active site. Because this type of activation is irreversible, other... 

A different type of covalent regulation of enzyme activity is the enzyme-catalysed activation of inactive precursors of enzymes (zymogens) to give catalytically active forms. The best examples are the digestive enzymes, e.g. trypsin. Proteolytic enzymes would digest the inside of the cells that produce the enzyme, so they are produced in an inactive form which is activated to the true enzyme once they have entered the digestive system of the animal. 

There are two general types of covalent modification of enzymes that regulate their activity. These are the irreversible activation of inactive enzyme precursors, the zymogens, and the reversible interconversion of active and inactive forms of an enzyme. 

Know the names and modes of action of all proteolytic enzymes and their zymogens, if any, and the hormones that regulate protein digestion understand the mechanisms of amino acid absorption and their disorders understand amino acid traffic patterns in the bloodstream, including their changes in the various dietary states and hepatic encephalopathy. 

Activation of a zymogen. Some enzymes are secreted as inactive precursors, called zymogens. Trypsin and pepsin are two such examples a portion of the zymogen must be cleaved off to form the active enzyme. Again, an on/ off switch more than a tight, variable regulation. 

The answer is e. (Murray, pp 48—73. Scriver, pp 2863—2914. Sack, pp 3—17. Wilson, pp 361-370.) Many enzymes interact to regulate blood clotting. Plasmin is activated by proteolytic cleavage of its zymogen, plasmino-... 

Nonallosterlc mechanisms for regulating protein activity Include proteolytic cleavage, which irreversibly converts inactive zymogens into active enzymes, compartmentation of proteins, and signal-Induced modulation of protein synthesis and degradation. 

Blood clotting is a situation in which the enzymes needed to form a clot must be present in the blood and ready to act rapidly when trauma to a blood vessel occurs. However, clots must not form in normal blood vessels or a heart attack or stroke will occur. The blood-clotting system is a complex and highly regulated mechanism which uses many steps of zymogen activation, with more examples of serine proteases. 

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