University:
Kentucky State University
Course:
CHE 315 | Biochemistry
Academic year:

2019
Views:

453

Pages:

19
Author:

omiliar74be

Enzyme Inhibition What do we mean by inhibitors? Enzyme Inhibition • Enzyme inhibitor: any substance that can reduce the velocity of an enzyme-catalyzed reaction and cause a loss of catalytic activity • Inhibitors can be reversible or irreversible. - Reversible inhibitors bind to enzymes through a non-covalent bonds ➔ Upon dilution the EI (enzyme-inhibitor) complex dissociate and recover the enzyme activity, may be competitive or noncompetitive - Irreversible inhibition occur when the inhibited enzyme can not recover its activity by dilution. The inhibitors form a covalent bonds with the active site enzyme or destruction of the protein structure of the enzyme Irreversible Inhibitors Competitive inhibitors This type of inhibition occurs when the inhibitors bind reversibly to the same site that the substrate normally occupy ➔ compete the substrate for that site A competitive inhibitor •Has a structure similar to substrate •Occupies active site •Competes with substrate for active site •Has effect reversed by increasing substrate concentration Competitive inhibitors Vmax: the effect of the competitive inhibitors is reversed by increasing [S]. At sufficient high substrate concentration [S], the reaction velocity reaches the Vmax observed in the absence of the inhibitors. The y-intersect is unchanged Km: a competitive inhibitors increases the apparent Km for a given substrate➔ in the presence of these inhibitors →more substrate is needed to reach the Vmax. The x intersect is changed indicating that the apparent Km is increased Non-Competitive Inhibitors Inhibitor binds at a site distinct from the substrate site It may bind to free E or to ES. Once bound it will prevent P formation. And the affinity of the I to both E and Es is the same. Noncompetitive Inhibition • Non competitive inhibition occurs when the inhibitor at a site distinct from the substrate site • A noncompetitive inhibitor does not have a structure like substrate. • Alter the shape of enzyme and active site➔ Substrate cannot fit altered active site • It binds either to the enzyme or to the ES complex ➔No reaction occurs • Effect is not reversed by adding substrate • It may bind to free E or to ES. Once bound it will prevent P formation. • And the affinity of the I to both E and ES is the same. • Non-competitive inhibitors decrease the Vmax, and can not be overcome by increasing the substrate concentration • Non-competitive inhibitors don’t affect the Km, the enzyme show the same Km in the absence or the presence of the inhibitors Enzyme inhibitors could be used as drugs Different types of enzyme inhibitors I2 I1 NONCOMP COMP I0 Enzyme inhibitors could be used as drugs Allosteric Enzymes and Allosteric Regulation Allosteric enzymes: are regulated by molecules called effectors (modulators) that bind noncovalently at site other than the active site. - Allosteric enzymes show Sigmoidal curve and don't follow Michalaelis-menten rules - Allosteric modulators affect the enzyme affinity to its substrate and /or modify the maximal catalytic activity of the enzyme - Enzyme regulation is essential to coordinate the numerous metabolic processes -Most of enzymes respond to changes of substrate concentration ➔ an increase in the substrate conc. lead to increase in the rate of enzyme action ➔ return the substrate conc. to normal level -Some enzymes respond to allosteric effectors or covalent modification that affect the velocity of enzyme Allosteric regulators (effectors) -Effectors that inhibit enzyme activity are termed negative effectors while those increase the enzyme activity are called positive effectors - Homotropic effectors: •The substrate itself acts as effector, usually allosteric substrate are positive effector. •The presence of substrate molecule at allosteric site will increase the catalytic activity of the substrate-binding site ➔ sites cooperativity ➔ Sigmoidal curve of V vs [S] not hyperbolic -Heterotropic effectors The effectors are different from substrate Feed back inhibition A→ B→ C→ D→E This enzyme has allosteric site that can bind to E The final product may have a feedback inhibition of on the enzyme that convert A→B Feed back inhibition serves to coordinate the flow of substrate molecules through a series of reactions with the need of the cell. Enzymatic Regulation Covalent modification-Protein phosphorylation - Many enzymes may be regulated by covalent modification; addition or removal of phosphate group -Phsphorylation occurs at the –OH of serine, threonine or tyrosine residues - Phosphorylation process could be Activation or Deactivation process ➔ depending on the enzyme itself active Inactive or Induction and repression of enzyme synthesis •Cells can regulate the amount of the enzyme present, usually by altering the rate enzyme synthesis •The induction or repression synthesis of protein leads to an alteration of the total number of enzyme population ➔ •increasing the number of active sites and •Not affecting the enzyme activity.

Biochemistry 1 Enzyme Inhibition

Related Documents

Recommended Documents

Description

Related Documents

Free up your schedule!

Take 5 seconds to unlock