BIOCHEMISTY Course No DTC111 BINITA RANI ASSOCIATE PROFESSOR

BIOCHEMISTY Course No. -DTC-111, BINITA RANI ASSOCIATE PROFESSOR (DAIRY CHEMISTRY) FACULTY OF DAIRY TECHNOLOGY S. G. I. D. T. , BVC CAMPUS, P. O. - BVC, DIST. -PATNA-800014 Credit Hours – 2 (1+1) ZYMOGENS AND RIBOZYMES

Zymogens Ø Several enzymes are synthesised as larger inactive precursor forms => proenzymes or zymogens. Ø Activation of zymogens involves => irreversible hydrolysis of => one or more peptide bonds. Ø The biochemical change usually occurs in a lysosome where => a specific part of the precursor enzyme is => cleaved in order to activate it.

Ø amino acid chain that is released upon activation is => called activation peptide. Ø pancreas secretes zymogens partly => to prevent the enzymes from digesting proteins in the cells in which they are synthesized. Ø Fungi also secrete digestive enzymes into => environment as zymogens. Ø external environment has a different p. H than inside the fungal cell and => this changes => zymogen's structure into an active enzyme.

Digestive Enzymes as Zymogens Ø Digestive enzymes trypsin, chymotrypsin and elastase => produced as zymogens in => pancreas. Ø They are transported to => small intestine as their zymogen forms and => activated there by => cleavage of specific peptide bonds. Ø Trypsin is synthesized initially as => zymogen trypsinogen.

Ø It is cleaved (and hence activated) in => intestine by => enzyme enteropeptidase which is only produced in the intestine. Ø Once activated trypsin can => cleave and activate further trysinogen molecules as well as other zymogens => such as chymotrysinogen and proelastases. Ø The peptidase in the stomach is pepsin => works optimally in the acidic environment of the stomach => being active at p. H 2 -3 but => becoming inactivated when the p. H is above 5.

Ø The chief cells at the base of the gastric glands secrete => zymogen => called pepsinogen. Ø Pepsinogen is partially activated by => hydrocholoric acid (HCl) => which is secreted by the parietal cells. Ø This partially active enzyme => cleaves the peptide from other pepsinogen molecules to => form active pepsin.

Digestive enzymes as zymogens

Biological Significance of Zymogens Ø Zymogens : Inactive Precursor Proteins. Ø A clinically important mechanism of controlling enzyme activity is => the case of protease enzymes involved (predominantly) in => food digestion and blood clotting.

Ø Activation of zymogens by proteolytic cleavage result in => irreversible activation Ø Zymogen forms allow proteins to be transported or stored in => inactive forms that can be readily converted to => active forms in response to some type of cellular signal.

Ø Thus they represent a mechanism whereby => the levels of an enzyme/protein can be rapidly increased (post- translationally). Ø Other examples of zymogens include => proinsulin, procollagen and many blood clotting enzymes.

Ribozymes Ø Before the discovery of ribozymes => enzymes, which are defined as catalytic proteins were => only known biological catalysts. Ø First ribozymes were discovered in 1980 s by => Thomas R. Cech => who was studying RNA splicing in the ciliated protozoan Tetrahymena thermophila and Sidney Altman => who was working on the bacterial RNase P complex.

Ø These ribozymes were found in => intron of an RNA transcript => which removed itself from the transcript, as well as in the RNA component of the RNase P complex => which is involved in the maturation of pre-t. RNAs. Ø Ribozymes often have divalent metal ions such as Mg 2+ as cofactors.

Ø A ribozyme (from ribonucleic acid enzyme => also called RNA enzyme or catalytic RNA) is => an RNA molecule that catalyzes a chemical reaction. Ø Many natural ribozymes catalyze => either hydrolysis of one of their own phosphodiester bonds => or hydrolysis of bonds in other RNAs. Ø They have also been found to aminotransferase activity of the ribosome. catalyze =>

Ø Investigators studying the origin of life have produced ribozymes in the laboratory => that are capable of => catalyzing their own synthesis under very specific conditions => such as an RNA polymerase ribozyme. Ø Some ribozymes may play an important role as => therapeutic agents => as enzymes which tailor defined RNA sequences, as biosensors, and => for applications in functional genomics and gene discovery.

Activity Ø Although most ribozymes are quite rare in the cell => their roles are sometimes essential to life. Ø For example => functional part of the ribosome => the molecular machine that => translates RNA into proteins => is fundamentally a ribozyme => composed of RNA tertiary structural motifs => that are often coordinated to metal ions such as Mg 2+ as cofactors. Ø There is no requirement for => divalent cations in a fivenucleotide RNA that can catalyze => trans-phenylalanation of a four-nucleotide substrate => which has three base complementary sequence with the catalyst.

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