MASTER PIECE FOR METABOLIC PATHWAYS : THE ENZYME

About Authors:
*C.P. Meher,  S.P.Sethy, B.Pochaiah
Department of pharmaceutical Bio-Chemistry,
Maheshwara college of Pharmacy, chitkul (V),
Isnapur “X” Road,  patancheru, Hyderabad.
*chaitanyameher84@gmail.com

ABSTRACT :-
“Enzyme are the catalyst of the living world ! protein in nature, and in action in specific ,rapid and accurate; huge in size but with small active centers; highly exploited for disease diagnosis in lab centers”[1] Enzyme promotes & control the conversion of the complex carbohydrates, fats & protein of our body into simple substances which the intestine can absorb & also the various reaction by which these simple substances are used in the body for building up new tissue  or producing energy. The enzyme are not broken down or changed in the process . they are as potent at the end of the reaction at the beginning & very small amounts can effect the conversion of large quantity of material . they are the true catalyst.[2] They are actively take part in every metabolic pathways that occur in our body. This review is concern with comparative study of the various enzyme related with various metabolic pathways as well as the drugs associated for inhibition to give respective pharmacological responses.

Reference Id: PHARMATUTOR-ART-1521

INTRODUCTION:-
Hundred of reaction simultaneously takes place in a living cell in a well organized and integrated manner. The entire spectrum of chemical reaction, occurring in the living system, are collectively reffered as metabolism. a metabolic pathway or metabolic map constitutes a series of enzymatic reactions to produce specific product. The metabolic reaction are mainly devided as oxidation-reduction,group transfer,rearrangement and isomerization & make-break of carbon-carbon bonds. these reaction are catalysed by specific enzyme-more than 2000 known so far. recently advances in biotechnology have made it possible to modify the enzyme with desirable characters improved catalytic abilities, activities under unusual conditions this approach is require since enzyme possess enormous potential for their use in medicine & industry.it is possible to rearrange genes and produce fusion proteins e.g.a hybrid enzyme (of glucanase & cellulose) that can more efficiently hydrolyse barley β- glucans in beer manufacture. Site-directed mutagenesis used to produce a specified mutation at a predetermined position in a DNA molecule. The result is incorporation of a desired amino acid in place of the specified amino acid in the enzyme .by this approach it is possible to produce an enzyme desirable characteristic . In recent year, it has also become possible to hybrid enzyme by rearrangement of genes. another innovative approach is the production of abenzyme or catalytic antibodies, the antibody enzymes. Enzyme activity basically depend on its properties like reaction specificity, Optical specificity, Bond specificity, group specificity & on several factors like contact between enzyme & substrate, concentration of enzyme & substrate, temperature, hydrogen ion concentration, oxidation, radiation, coenzyme and activators, inhibiting agents, anti enzyme.

If the concentration of substrate increases, more and more active sites of enzyme molecule will be used for formation for enzyme substrate complex the rate of reaction will increase. Enzymes are substrate specific. They act on specific group of enzyme for catalytic activity. Few examples are listed below in table-1[3]

Table-1

Enzymes plays an important role in the various metabolic pathways. They are present there as coenzymes with some other group attached to them having substrate specificity to accelerate the particular metabolic reaction apart from that various co-factors also played important role in enhancing their mechanism of action. Particular type of metabolic reaction carried out by particular enzyme like the digestion of food ,in that food is comprises of different components eg. carbohydrates they act upon by enzymes like maltase, sucrase, galactases etc. to breakdown into simple sugar.

Enzymes also plays an important role in DNA and RNA synthesis like ribonucleotide reductase to convert ribonucleic acid into deoxyribonucleic acid and reverse transcriptase to form cDNA from mRNA.

Many enzymes requires a metal ion for activity. In some cases the requirement is specific for a particular metal. Carbonic anhydrase shows no activity upon removal of zinc & no other metal is known to replace zinc in this enzyme. in other cases more than one metal is able to bring activation; for example mg2+.mn2+or zn2+ activate enolase (2-phosphoglycerate--àphosphoenol pyruvate+ H2O).in a few cases it appear that two metal ion may be required by the enzyme for ex-,pyruvate phosphokinase requires both mg2+  & k+(pyruvate+ATP---àPhosphopyruvate+ADP)[4]. Examples are listed below in table-2[3].

Table-2

The catalytic power of an enzyme is measured by the “turn over” or molecular activity which is defined as the number of substrate molecule converted into product per unit time when the enzyme is fully saturated with substrate .however, for most enzyme , the turn over number fall between 1 to 10⁴   per second.Examples are listed below in table-3[5]

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Table-3        

Most drugs are metabolized by many pathways, rate of reaction by different pathways often vary considerably. A variety of metabolites (some more , some less) of a drug may be produced. Only a few drugs are metabolized by enzymes of intermediary metabolism. the drug metabolizing enzymes are  devided into microsomal enzyme responsible for oxidation-reduction, hydrolysis, glucuronide conjugation (inducible by drugs ,diet, other agencies) & non-microsomal enzyme responsible for  some oxidation-reduction, many hydrolytic reactions, all conjugation except glucuronide conjugation(not inducible ,show genetic polymorphism).the amount and kind of drug metabolizing enzyme is controlled genetically and is also altered by environmental factors. it is also seen that inactivation of the drugs in the body fluid by spontaneous molecular rearrangement without the agency of any enzyme occur.(Holfmann elimination).[6]

There are two types of enzyme controlled reactions:
Degradation (catabolic) when an enzyme breaks down large molecules into smaller ones.eg. digestion. Synthesis (anabolic) when the enzyme builds up larger molecules from smaller ones. eg photosynthesis or protein synthesis.

Enzymes are specific, which means each enzyme only catalyses one reaction. This is because the enzyme molecule is folded in a particular shape with a portion called an active site to which only the correct substrate molecule can attach, much like a key in a lock.

E= Enzyme, S = Substrate, ES = Enzyme /Substrate complex, P = Product(s)

E + S ---> ES ---> P + Unaltered E

Like all proteins, enzyme action is determined by their shape. Extremes of temperature and pH distorts the shape and the substrate can no longer fit in the active site, so the enzyme will no longer work, it is said to be denatured. This is a permanent change. The Temperature that an enzyme works best is called the Optimum e.g 37oC for human enzymes.

Metabolic pathways and regulatory enzymes
Many metabolic reactions occur in a series of steps (e.g. glycolysis) and the rate at which a substrate is used, or a product formed, can be controlled by altering the rate at which enzymes work. Some enzymes in the pathway are more important than others in the regulation of the rate of reaction along the pathway. These may be compared to variable speed controls along a motorway. The targeted enzymes are called regulatory enzymes. They often occur at the first step in a metabolic pathway. Various metabolic pathway that occur inside the body fluid  along with the major regulatory enzyme are listed below in table-4 [2]

Table-4

Table-5[2
The various tissue and organ of the body work in a well co-ordinated manner to meet its metabolic demand. The major organ with their function & which enzyme is responsible for the metabolic pathways are described in table-5 .Now-a-days several drugs are available in the market which has the capabilities to inhibit the enzymes that are associated with the several metabolic pathways by which they are giving certain number of pharmacological effect. so the enzymes are the target molecules. below a table is given(6) listing the enzyme inhibited along with the pharmacological effects.

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A Partial Listing of Enzyme Inhibitor Drugs Presently Used as Drugs

Table-6