Enzymes zymogens

Enzyme Zymogen molecular weight Collagenase activity (K,IK X 7, M- min ) Protein substrates Human cells producing enzyme Reference to sequence... 

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. 

Enzyme Zymogen Source Size of fragment removed during activation Means of activation Specificity... 

The mammalian pancreatic enzymes (group IB) have primarily a digestive role and are secreted as the pro-enzyme (zymogen) that requires subsequent proteolytic cleavage to remove a hexapeptide at the N-terminus. The pro-enzyme is unable to bind to the phospholipid interface. Unlike the cobra venom enzyme, the pancreatic enzyme expresses low activity with a zwitterionic interface such as that provided by phosphatidylcholine. The enzyme has a considerable preference for an anionic interface that can be provided by anionic phospholipid per se or by the inclusion of other anionic lipids in the... 

Spande, T. F., N. M. Green, and B. Witkop The Reactivity toward N-bromo-succinimide of Tryptophan in Enzymes, Zymogens, and Inhibited Enzymes. Biochemistry 5, 1926-1933 (1966). 

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. 

Why do you suppose proteolytic enzymes are often synthesized as inactive zymogens ... 

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. 

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

Autolysis of the pancreas can occur when zymogens are activated in the pancreas before being released into the duodenum. Acute pancreatitis can result from the initial injury to the zymogen-producing cells, which is followed by neutrophil invasion of the pancreas, and that ends in further activation of enzymes within the pancreas. This cascade of events can be destructive to the pancreas and harmful to the patient. 

Zymogen A proenzyme the inactive or nearly inactive precursor of an enzyme that is converted into an active enzyme by proteolysis. 

Procarboxypeptidase A is activated by the removal of a peptide of some 64 residues from the N-terminus by trypsin.153 This zymogen has significant catalytic activity. As well as catalyzing the hydrolysis of small esters and peptides, procarboxypeptidase removes the C-terminal leucine from lysozyme only seven times more slowly than does carboxypeptidase. Also, the zymogen hydrolyzes Bz-Gly-L-Phe with kcsA = 3 s-1 and KM = 2.7 mM, compared with values of 120 s 1 and 1.9 mM for the reaction of the enzyme.154 In contrast to the situation in chymotrypsinogen, the binding site clearly pre-exists in procarboxypeptidase, and the catalytic apparatus must be nearly complete. 

The matrix metalloprotease (MMP) family of zinc hydrolases are thought to play important roles in extracellular tissue remodeling in angiogenesis and other normal physiological processes, in some inflammatory processes and in metastatic processes in cancer. Like the zinc carboxypeptidases, the MMPs also utilize a zinc-coordinated water molecule to initiate attack on the scissile amide bond of protein substrates. These enzymes are synthesized by the ribosome in a latent form composed of a catalytic domain and an N-terminal extension, referred to as the prodomain the latent, or inactive form of the enzyme is referred to as a zymogen or... 

Activity-based protein profiling (ABPP) is a chemical proteomic strategy in which active-site-directed covalent probes are used to profile the functional states of enzymes in complex proteomes. Activity-based probes (ABPs) can distinguish active enzymes from their inactive zymogens or inhibitor-bound forms. They contain a reactive group intended to modify enzyme active sites covalently and a reporter group (typically rhodamine or biotin) that assists in detection and identification of protein targets. 

AP is initiated by premature activation of pancreatic zymogens (inactive enzymes) within the acinar cells, pancreatic ischemia, or pancreatic duct obstruction. 

Cathepsin K (Cat K) is a member of the CA1 family of lysosomal cysteine proteases. This family is comprised of 11 human members (cathepsins B, C, F, H, K, L, O, S, V, W, Z) which share a common papain-like structural fold and a conserved active site Cys-Asn-His triad of residues [1-3]. These enzymes are synthesized as pre-pro-enzymes and are converted from the catalytically inactive zymogen into the active form in acidic lysosomal environment. In some cases, cathepsins are also secreted in the active form from cells. The sequence identity of... 

To cite an example, this strategy was also used to activate methotrexate-Phe (6.36, R=Phe) and other methotrexate-a-peptides in the vicinity of tumor cells [64], Carboxypeptidase A is normally synthesized as a zymogen that is inactive without proteolytic removal of its propeptide end by trypsin. To adapt this system to GDEPT, a mutant form of the enzyme (CPASX3) was... 

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