1. Inhibitors: ( - ve modulators )
Are substances, which cause inhibition of enzyme activity or decrease the velocity of the enzyme catalyst reaction .inh. are classified into two classes:
1-Competitive inhibitors:
Are substances usually have similar in the structure with the substrate and therefore they may be called substrate analogue and so there will be competition between substrate and inh. For binding with the substrate binding site of the enzyme .In the presence of competitive inh. change in enzyme kinetic will cause increase in Km will v-max stay constant .

3. Ex: Treatment of ethylene glycol poisoning by competitive inhibitors .
Ethylene glycol ( anti freeze) Itself is not toxic, rather the harm is done by oxalic acid , an oxidation product of ethylene glylycol . the first step is the oxidation of ethylene glycol by alcohol dehydrogenase. This reaction can be effectively inhibited by the administration of nearly intoxicating dose of ethanol .the basis of this reaction is that ethanol act as competitive inhibitor of oxidation of ethylene glycol to adehyde product. The same reaction is used in therapy of methanol The same reaction is used in therapy of Methanol poisoning.
CH2OH—CH2OH---CHO—CH2OH---COOH—COOH oxalic acid (toxic)alcohol dehydrogenase inhibited by ethanol

5. II-non- competitive inhibitors:
These inh. have similar or no similar in the structure with substrate and therefore they will not compete with the substrate binding sites these inh. bound to the allosteric sites of the enzyme which are unaffected by substrate but they are importuned in showing the catalytic effect of the enzyme. These type of inh. still can show change in enzyme kinetic which include 1-km remain constant. II-decrease in v-max.ex:

6. Many drugs useful in medicine appear to function because they can inhibits or poisoned certain enzyme in tissues the compound (nerve gas) diisopropyl fluorophosphat DFP. which inhibits the enzyme choline esterase .Choline esterase catalyze the reaction which take place at the junction between certain cell in the nervous system or an enzyme play important role in transmission of nerve impulse .DFP combines with the hydroxyl group of serine residue in the active site of the choline esterase molecule F  OH-CH2-E (Choline esterase) (CH3)2CHO-P-O-CH(CH3)2 DFP O

7. Activators (+ ve modulators or cofactor ).
Non competitive inh. Include inhibition of many metabolic process in the body ex: poisoning by heavy metals such as mercury Hg and lead pb ,cd, (irreversible comp. Inh. )also poising by cyanid ,cyanide which combine reversibly with the iron atom of some iron contain enzyme to yield an inactive form .
Activators (+ ve modulators or cofactor ).
Ex: activation of lipase by the metal Ca.
In this reaction lipase hydrolyze the substrate ( triglyceride into F.A ) will cause inhibition the action of lipase , but by adding Ca +
Triglyceride lipase
Lipase
F.F.A. +Ca+2
Ca-F.F.A.complex
-ve inhibit activity of the E lipase

8. this metal Ca will form a complex with product ( F. F
this metal Ca will form a complex with product ( F.F.A) lead to the formation of Ca F. F.A Complex and this new product has no inhibitory effect on lipase .
Role of selective proteolysis in creation catalytic sites of the enzyme .
Many proteins in body including enzymes are manufactured in the body and secreted in an inactive form ,but following selective proteolysis process ( cleavage or clips process ) the active form of the protein will appear , where the protein is enzyme , its proportion form is called Proenzyme.

9. Pro/protein protein
Cleavage
Proenzyme or zymogen enzyme
Prohormone hormone
e.g. Inactive proteins in the body which are formed or manufactured in proportion forms :
Hormones : insulin ,glucagon
Enzymes : all digestive enzymes lick tyrosine , pepsin , and chymotrypsin
Blood clot formation
Connective tissue protein: collagen. During physiological need these inactive form convert to the active one.

10. Isoenzyme
These means enzyme multiplicity that is the presence of the some enzyme in multiple form .
These multiple form have the same catalytic properties but they are different in their physical properties ex: chorine esterase present in the erythrocyte and nerves tissue is different form the enzyme present in plasma and liver. There are six mechanisms that are responsible for appearance of isoenzyme:
1-genetically distinct or differ protein : which include by this mechanism each isoenzyme of the original enzyme is being genetically differ protein or amino acid composition and sequence from other isoenzyme of the same enzyme ex : of this mechanism include isoenzyme present in mitochondria and cytosolic isoenzyme like Asparatate transaminase (AST ) and Glutamate oxaloacetate transaminase

11. 2- Differences in subunit structure : Some enzyme may contain more than one structural subunit e.g Creation Kinase (CK) consist of two subunit called dimer either M or B , M because present in muscle while B present in brain . so CK can form three different isoenzyme from the possible combination of the dimer leading to isoenzyme or CK1 (BB) Which present mainly in the brain , CK2 (MB ) That is present in cardiac muscle CK3 (MM) which is present in skeletal muscle .anther e.g.
LDH enzyme is tetrameter formed of 4 structural subunit , which are two kinds of polypeptide chains either H subunit or M subunit which can form 5 types of tetrameter

12. H H H H (H 4) Present in the heart and erythrocyte . LDH 1 α1 28 (15-30)
H H H M (H 3 M ) LDH α (22-50)
H H M M ( H 2 M 2 ) LDH β (15-30)
H M M M ( H M 3 ) LDH γ 6
M M M M ( M 4 ) LDH γ (0-15 ) elevated in acute hepatitis ,acute muscle injury ,muscular dystrophies.

13. Thus skeletal muscle is rich in isoenzyme that has the highest affinity for pyruvate and conversion it most rapidly to lactate ( Km is low ) .
3- Isoenzyme due to allelic variation :
enzyme might appear in more than in one form due to ( a point of mutation ) that include replacement of one amino acid sequence by another amino acid that lead to the appearance of enzyme in more than one isoenzyme ex: glucose –6- phosphate dehydrogenase which is present in two form : A form , B form
A form ( contain Aspartic acid ) B form ( contain Aspargin )
4-combination with charged group : ex : Alkaline phosphates is present in multiple form -(isoenzyme ) due to the different in combination of these isoenzyme with charged group. Present in liver , bone , intestine , placenta .

14. 5- Isomerism : some enzyme may appear in more than one form due to the formation of different isomers which may be positional or geometric isomers choline esterase present in more than one isoenzyme , present in nerve tissue , liver and erythrocyte , malate dehydrogenase ( MDH )
6- Polymerization : due to different in the aggregation of different amino acid ex: choline esterase .