Functions of Enzymes

The enzymes perform a number of functions in our body. These include:

1. Enzymes help in signal transduction. The most common enzyme used in the process includes protein kinase that catalyzes the phosphorylation of proteins.
2. They breakdown large molecules into smaller substances that can be easily absorbed by the body.
3. They help in generating energy in the body. ATP synthases are the enzymes involved in the synthesis of energy.
4. Enzymes are responsible for the movement of ions across the plasma membrane.
5. Enzymes perform a number of biochemical reactions, including oxidation, reduction, hydrolysis, etc. to eliminate the non-nutritive substances from the body.
6. They function to reorganize the internal structure of the cell to regulate cellular activities.

Enzyme Inhibition

Enzymes can be inhibited in it action both invivo and invitro.

Inhibition are reducing reaction rates via binding of non-substrate molecule.

  Types and classes of inhibitors:

    1. IRREVERSIBLE – inhibitor molecule can not be easily removed from enzyme

             thereby reducing the number of working enzyme molecules. 

             i.e, enzyme is physically altered by binding of inhibitor – reducing its amount

                             alkylating agents like iodoacetamide (bind to -SH’s)

                             organophosphorous compounds- nerve gases (bind to SER)

                    some antibiotic drugs, such as penicillin form covalent link to active site

    2. REVERSIBLE – enzyme activity may be restored by removing the inhibitor

               and are thus treatable by M & M kinetics

                     2 major types of reversible inhibitions…

                            a.   COMPETITIVE

                            b.  NON-COMPETITIVE

COMPETITIVE  INHIBITION…

    inhibitor binds to E & forms an [EI] complex at the active site     ecb 3.29*

    inhibitor often looks like substrate… fools active site & binds

    extent of inhibition is concentration dependent,  [inhibitor is at fixed conc]

                              i.e., it can be overcome if [S] is very high,   i.e., [S] >>> [I]

                            one classical example is malonic acid inhibition of SDH

                            easy to demonstrate is via Lineweaver-Burk plots*

                            µ        shows Vmax is SAME,   but  Km  value is increased

  b.  NON-COMPETITIVE  INHIBITION…

    inhibitor binds to E, forms an [EI] complex not at the active site

    inhibitor often bears no structural relationship to substrate

    removes a net amount of active enzyme, i.e., lowers total [E]

                            i.e., it can NOT be overcome, even if [S] is very high

                          easy to demonstrate via Lineweaver-Burk plots

            µ  shows Km is SAME  &   Vmax is different  

Some Examples of Enzyme Inhibition:

  1. Irreversible Enzyme Inhibition & Mechanism of Action of Some Antibiotics…

     Antibiotic – a natural molecule (often made by bacterial cells) that can kill other

    bacterial cells (& without hurting eukaryotic cells: they’re insensitive)

     Penicillin – any one of a group of antibiotics derived from the fungus Penicillium. The action

     of natural penicillin was first observed in 1928 by British bacteriologist Alexander Fleming,

      and recognized as anti-bacterial by Howard Florey and others.

             Penicillin is a substrate-like molecule* similar to bacterial peptidoglycans, which

      naturally cross-link in the bacterial cell walls & favor rigidity.

      penicillin  works by IRREVERSIBLE binding to active site of enzymes that link

      peptidoglycans; forms covalent link, removing enzyme, reducing

      its Vmax; weakens bacterial walls eventually rupture & cells die.

2. Competitive Enzyme Inhibition  and  Mechanism of Drug Action

         ACE Inhibitors – drugs that bind to the enzyme’s active site & reduces its activity

           ACE – Angiotensin Converting Enzyme: a proteolytic enzyme that cuts Angiotensin I

            a polypeptide of 10 amino acids to Angiotensis II (of 8 amino acids).

           Angiotensin II promotes hypertension ( high blood pressure – HBP ) via vasoconstriction

           in 1960’s John Vane discovered TEPROTIDE in Brazilian pit viper venoms, a

          nonapeptide (9aa = Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) which functions as

         ACE competitive inhibitor, by binding to the active site of the ACE enzyme.

Thanks

Dr.U. D Enyidi   

Lecturer