AUSTRALIAN NATUROPATHIC NETWORK
 Serving the community since 1998

‘This is enzyme weather.’

A visiting American professor of medicine when temperatures were nearing 40° C.

Introduction

Enzymes are proteins that accelerate (catalyse) biochemical reactions¹. They are present throughout the human body and have a multitude of functions ranging from digestion of food to aiding with the elimination of toxins. There are thousands of enzymes and many more catalysed reactions for which enzymes are yet to be found.

Definitions

Enzymes are typically large proteins which are structured specifically for the reaction they catalyse. Their size provide sites for action and stability of the overall structure.

Two identified sites within enzymes are:

The catalytic site, which is a region within the enzyme involved with catalysis¹, and

The substrate binding site which is the specific area on the enzyme to which reactants called substrates bind to.

The catalytic site and substrate binding site are often close or overlapping¹ and collectively they are called the active site. If the catalytic site is not near the substrate binding site it can move into position once the enzyme is bound to a substrate.

Often enzymes require additional components to become active. These may be:

co-factors - simple cations, or small organic or inorganic molecules that bind loosely to the enzyme,

prosthetic groups – similar to co-factors but more tightly bound to the enzyme, or

co-enzymes – which are more complex than co-factors and prosthetic groups, they often act as a second substrate or bind covalently with the enzyme to affect the active site.

The enzyme must have additional binding sites for the additional components. Enzymes lacking essential additional elements are called apoenzymes, whereas intact active enzymes are called holoenzymes.

Classification

The names of enzymes, both common and systematic, are controlled by the Enzyme Commission¹. The common name is often derived by simply adding the suffix ‘-ase’ to the name of the substrate upon which it works.

The Systematic Scheme of Classification was adopted by the International Union of Biochemistry in 1961. An enzyme is designated by four numbers, main class, subclass, sub-subclass, and serial number, separated by periods. The six main classes of enzymes are presented in Table 1.

Table 1 Classes of enzymes

An example of the systematic name of an enzyme is presented in Table 2.

Table 2 Example of enzyme name

Mechanisms of Action

The catalytic power of enzymes depend on their ability to ‘lower the activation barrier separating reactants and products’². That is the energy required to cause a reaction to occur is lower when an enzyme is present. In order to achieve this enzymes:

May provide an environment favourable to the reaction,

May cause intermediate reactions that step toward the final product,

May act as acid/base catalysts (ie proton donors or proton acceptors), or

May covalently bond with the substrate and thus weaken other bonds within the substrate.

Enzyme catalysis usually occurs in three basic steps³:

Substate(s) recognise the enzyme and attaches in a specific arrangement called the enzyme-substrate complex.

The catalytic site comes into contact with the subtrate causing catalytic activity and the substrates are converted to products.

The products leave the enzyme.

The enzyme can participate repeatedly in this process.

In 1890 it was proposed that the shape of the substrate binding site is complementery to that of the substrate. This is known as the lock and key model of enzyme specificity³. The catalytic site acts on the substrate either because it is near the substrate binding site or because the enzyme alters shape once it is in contact with the substrate.

Many enzymes react with more than one substrate and the rigid the lock and key model is no longer valid. The induced fit model assumes that the substrate binding site is more flexible and adapts to fit different substrates to which the enzyme bonds⁴.

In cases where coenymes are required for the enzyme to become active slightly more complex mechanisms of action have been proposed.

The ping-pong mechanism sees an enzyme bind with one substrate, release its product, and alter its shape. The altered enzyme then binds to a second substrate, releases its product, and returns to its original shape. The process can then repeat.

A sequential mechanism requires that all substrates are bound to the enzyme for the reaction to take place. Some enzymes require substrates to bind in strict order, this is called an ordered mechanism. Other enzymes are less anal, and do not care about the order that the substrates bind in. This is called a random mechanism.

Enzyme Inhibition

Inhibition of enzymes results in a decrease in or elimination of the effect an enzyme has on the rate of a reaction. There are two main types of inhibitors reversible inhibitors and irreversible inhibitors¹.

Reversible inhibitors do not completely stop the enzyme from catalysing a reaction, and if the concentration of the inhibitor is lowered the enzymatic activity returns to its normal level¹. The reaction can still proceed but at a much slower rate, depending on the amount of inhibitor and substrate present. If concentrations of the inhibitor are lowered they tend to dissociate from the enzyme.

There are three mechanisms for reversible inhibition:

Competitive inhibition – where the inhibitor resembles the substrate and binds to the same point on the enzyme that the substrate would,

Non-competitive inhibition – where the inhibitor does not bind to the same point as the substrate but slows down the reaction regardless.

Uncompetitive inhibition – where the inhibitor binds to the enzyme when the substrate is already bound.

Irreversible inhibitors bind strongly to the enzyme usually via covalent bonds and do not dissociate when concentrations are lowered: thus their name. Bonding can occur at the active site or elsewhere on the enzyme¹, but the overall effect is to inactivate the enzyme. By definition it does not appear that competitive, non-competitive, or uncompetitive inhibition are terms used to refer to irreversible inhibition (after¹).

Conclusion

This brief paper again shows how the structure of proteins are crucial to the processes of life. Enzymes catalyse reactions that are critical to humans, from digestion to the elimination of toxins throughout the body.

References

Zubay, G., Biochemistry – 2^nd Edition, Macmillan Publishing Company, NY, 1989.

Colby, D. S., Biochemistry: A Synopsis, Lange Medical Publications, California, 1985.

Davies, J., Shaffer Littlewood, B., Elementary Biochemistry – An Introduction to the Chemistry of Living Cells, Prentice-Hall Inc, New Jersey, 1979.

Timberlake, K.C., Chemistry – 5^th Edition, Haper-Collins Publishers Inc, NY, 1992.