enzymes biochemistry

ENZYMES

Muhammad Ramzan Ul Rehman 1

Enzymes – are biologic catalysts.

Catalysts are substances that increase the speed of a chemical reaction, it is not permanently changed, nor does it cause the reaction to occur, that is, a catalyst can increase the speed of a reaction but cannot cause that reaction if it would not occur in the absence of catalyst. Since catalysts are not used up, they can be used over and over again.

OVERVIEW of ENZYMES


Enzymes – are organic catalyst produced by an organisms. The reactant in an enzyme-catalyzed reaction is called “substrate”.

OVERVIEW of ENZYMES


The small portion of the molecule that is responsible for the catalytic action of the enzyme is the “active site”.

OVERVIEW of ENZYMES


Enzymes are superior to other catalysts in several ways:

1. They have a much greater catalytic power.

CO2 + H2O carbonic anhydrase H2CO3

OVERVIEW of ENZYMES


2. Enzymes are highly specific with varying degrees of specifity.

Absolute specifity – they act on one substrate and only on that substrate.

Stereospecifity – such enzymes that can detect the difference between optical isomers (mirror images) and select only one of such isomers.

Reaction specifity – enzymes that catalyze certain types of reactions.

OVERVIEW of ENZYMES


Group specifity – enzymes that catalyzes a group of substances that contain specific compounds.

3. The activity of enzymes is closely regulated, whereas the catalyst is difficult to control.

OVERVIEW of ENZYMES


Enzymes are proteins and therefore undergo all the reactions that proteins do. That is, enzymes can be coagulated by heat, alcohol, strong acids, and alkaloidal reagents.

Temperature RequirementThe higher the temperature, the faster the

rate of reaction. The best temperature for enzyme function – the temperature at which the rate of a reaction involving an enzyme is the greatest – is called the “optimum temperature”.

ENZYME REACTION


Role of pHEach enzyme has a pH range within which it

can best function. This is called “optimum pH range” for that particular enzyme. For example, the optimum pH range of pepsin, an enzyme found in gastric juice, is approximately 2.0, whereas the optimum pH range of trypsin, an enzyme found in pancreatic juice, is near 8.2.

ENZYME REACTION


If the pH of a substrate is too far from the optimum pH required by the enzyme, that enzyme cannot function at all. However, since body fluids contains buffers, the pH usually does not vary too far from the optimum values.

ENZYME REACTION


Effect of Concentration

As with the all chemical reactions, the speed is increased with an increase in concentration of reacctants. With an increased concentration of substrate, the rate of the reaction will increase until available enzyme becomes saturated with substrate.

Also with an increase in the amount of enzyme, the rate of reaction will increase, assuming an unlimited supply of substrate.

ENZYME REACTION


Activators – inorganic substances that tend to increase the activity of enzyme.Inhibitors – any substance that will make the enzyme less active or render it inactive.

Competitive inhibitors – binds reversibly in the active site and so block the access by the substrate.

Incompetitive inhibitors – bind to another site on the enzyme to render it less active or inactive.

ACTIVATORS and INHIBITORS


Irreversible inhibitors – form strong covalent bonds with the enzymes, rendering it inactive. This effect can’t be overcome by increasing the concentration of the substrate.



Poisons Many enzymes inhibitors are poisonous

because their effect on enzyme activity. Mercury and Lead compounds are poisonous because they react with sulfhydryl groups ( - SH) of an enzymes and so change its conformation. The subsequent loss of enzyme activity leads to the various symptoms of lead and mercury poisoning, such as loss of equilibrium, hearing, sight, and touch, which are generally irreversible.



DrugsWhile some enzyme inhibitors are poisonous,

others are beneficial to life. Pencillin acts as an enzyme inhibitor for transpeptide, a substance that bacteria need to build their cell walls. If the cell wall is lacking, osmotic pressure causes the bacterial cell to burst and die. However, new strains of bacteria have developed an enzyme, penicillinase, that inactivates penicillin. To destroy these new strains, synthetically modified penicillins have been prepared so that this antibiotic remains effective.



MODE OF ENZYME ACTIVITY


Lock-and key Model

Wherein the substrate must “fit” into the active site of the enzyme – hence the specifity of the enzyme.

Induced-Fit Model

Suggests that the active site is not rigid as the Lock-and-Key Model, but flexible. That is, the site changes in conformation upon binding to a substrate in order to yield an enzyme-substrate fit.



Other enzymes are conjugated proteins – they contain a protein and non-protein part. Both parts must be present before the enzyme can function.

The protein part is called the “apoenzyme” and the non-protein (organic part) is called “coenzyme”.

APOENZYMES and COENZYMES


Coenzymesare not proteins and so are not inactivated by

heat. Examples of coenzymes are the vitamins or compounds derived from vitamins. The reaction involving a coenzyme can be written as follows:

coenzyme + apoenzyme = enzyme

Coenzyme A is essential in the metabolism of carbohydrates, lipids, and proteins in the body.

APOENZYMES and COENZYMES


Formerly enzyme were given names ending in “-in”. With no relation being an indicator between the enzyme and the substance it affects – the substrate.

The current system for naming enzymes uses the name of the substrate or the type of reaction involved, with the ending “-ase”.

NOMENCLATURE


ENZYME SUBTRATE or REACTION TYPE

Maltase Maltose

Urease Urea

Proteases Proteins

Carbohydrases Carbohydrates

Lipases Lipids

Hydrolases Hydrolysis Reaction

Deaminases Removing amines

Dehydrogenases Removing hydrogens

NOMENCLATURE


Oxidoreductases – are enzymes that catalyze oxidation-reduction reactions between two substrates. The enzymes of the oxidation-reduction reactions in the body are important because these reactions are responsible for the production of heat and energy.

Transferases – are enzymes that catalyze the transfer of a functional group between two substrates.

CLASSIFICATION


Hydrolases – hydrolytic enzymes – catalyze the hydrolysis of carbohydrates, esters and

proteins.

Lyases – are enzymes that catalyzes the removal of groups from substrates by means other than hydrolysis, usually with the formation of

double bonds.

CLASSIFICATION


Isomerases – are enzymes that catalyze the interconversion of cis-trans isomers.

Ligases – or synthetases, are enzymes that catalyze the coupling of two compounds with breaking of pyrophosphate bonds.

CLASSIFICATION


If an individual’s blood pressure drops, as in the case of hemorrhaging or in hypokalemia, the kidneys secrete the enzyme renin (sometimes considered as a hormone) into the bloodstream.

angiotensinogen renin angiotensin I converting enzyme angiotensin II

Angiotensin II increases the force of the heartbeat and constricts the arterioles, thus causing an increase in blood pressure.

ENZYMES of the KIDNEY


Angiotensin II brings about the contraction of smooth muscle and also triggers the release of the hormone aldosterone which aids in the retention of water. Actually, angiotensin I is the most powerful vasoconstrictor known. It is an octapeptide; Angiotensin I is a decapeptide.



Other kidney enzymes include glucose-6-phosphatase, which is involved in the removal of the phosphate group from glucose-6-phosphate, thereby enabling glucose to diffuse from the cell into the blood stream;

Glutaminase, which is involved in the conversion of glutamine into glutamic acid and NH4+ ; and a

hydroxylase, which is involved in the synthesis of calcitriol.



Chemotherapy is the use of chemicals to destroy infectious microorganisms and cancerous

cells without damaging the host’s cells. These chemicals function by inhibiting certain cellular enzyme reactions. Among the chemotherapeutic agents are the antibiotics and the antimetabolites.

CHEMOTHERAPY


Antibiotics – are compounds produced by one microorganisms that are toxic to another microorganisms. Among the most commonly used are the penicillin and tetracyclin.

CHEMOTHERAPY


ENZYMES Elino, M.M.H.

CHEMOTHERAPY

Penicillin

Tetracycline


Antimetabolites – are chemicals that have structures closely related to those of the substrate enzymes act on, thus inhibiting enzyme activity.

Mercaptopurine are used in the treatment of leukemias. Some are antibiotics.

CHEMOTHERAPY


One of the most promising new chemotherapeutic agent in decades is taxol, a natural product obtained from the bark of Pacific yew trees. Taxol acts by interfering with cellular growth and function and is very effective in shrinking a variety of tumors, particularly in advanced cases of ovarian and breast cancer.

CHEMOTHERAPY


The measurement of plasma enzyme levels can be of great diagnostic value. Many other plasma enzymes are useful in the diagnosis of various diseases.

CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS



SERUM ENZYME MAJOR DIAGNOSTI C USE

Glutamic oxaloacetic transaminase (SGOT)

Myocardial Infarction

Glutamic pyruvic transaminase (SGPT)

Infectious Hepatitis

Trypsin Acute pancreatic disease

Ceruloplasmin Wilson’s Disease



SERUM ENZYME MAJOR DIAGNOSTI C USE

Amylase Liver and pancreatic disease

Acid phosphate Prostate Cancer

Alkaline phosphatase Liver or bone disease

Creatine phosphokinase Myocardial infarction, muscle disorders

Lactate dehydrogenase Myocardial Infarction, leukemia, anemia

Renin HypertensionMuhammad Ramzan Ul Rehman 36

Isozymes or Isoenzymes are enzymes with the same function but

slightly different structural features. The reason for their existence is not unknown, but they are made use of clinically. Lactate dehydrogenase (LDH), creatine kinase, and alkaline phosphatase all occur in isoenzyme form and are diagnostic value. LDH has five forms.

ISOZYMES


CLINICAL SIGNIFICANCE OF RELATIVE AMOUNT OF LDH

Condition Isoenzyme Pattern

Myocardial InfarctionModerate elevation of LDH1;

Slight elevation of LDH2

Acute HepatitisLarge elevation of LDH5;

Moderate elevation of LDH4

Muscular Dystrophy Elevation of LDH1, LDH2, LDH3

Megaloblastic Anemia Large elevation of LDH1

Sickle-cell Anemia Moderate elevation of LDH1, LDH2

Arthritis with Joint effusions Elevation of LDH5


ALLOSTERIC REGULATION

Allosteric regulation is the regulation of an enzyme or

other protein by binding an effector molecule at the enzyme's allosteric site (that is, a site other than the active site).

Effectors that enhance the protein's activity are referred to as allosteric enzymes, whereas those that decrease the protein's activity are called noncompetitive inhibitors.


ALLOSTERIC REGULATION

Allosteric regulation This control of key enzymes is utmost

importance to ensure that biologic processes remain coordinated at all times to meet the immediate metabolic needs of the cells.


ZYMOGENS

Zymogensare inactive pprecursors of enzymes.

Most digestive and blood-clotting enzymes exist in the zymogen form, until activated.

In the case of digestive enzymes, this is necessary to prevent digestion of pancreatic and gastric tissue. For blood clotting, it is to avoid premature of blood cells.


ZYMOGENS

ZYMOGEN ACTIVE FORM OF ENZYME

pepsinogen pepsin

trypsinogen trypsin

prothrombin thrombin


ZYMOGENS

Lactose IntoleranceIndividuals who cannot eat food

containing lactose are said to be lactose intolerant.They lack enzyme lactase, which is requires for the hydrolysis of lactose.

As a result, lactose acuumulates in the intestinal tract and pulls water out of the tissues by osmosis. This is turn causes abdominal cramps, distention, and diarrhea.


ZYMOGENS

Lactose Intolerance

To overcome such an effect today, an individual may take Lactaid orally to supply the missing enzyme.


GOD BLESS!


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