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Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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12 Non-Enzymatic Biological<br />

Catalysis<br />

12.1 <strong>Introduction</strong><br />

In the Wnal chapter I wish <strong>to</strong> address the question: are enzymes unique in their<br />

ability <strong>to</strong> catalyse biochemical reactions The discovery of enzymes <strong>and</strong> the<br />

elucidation of their function provides a basis for underst<strong>and</strong>ing how cellular<br />

biological chemistry can be catalysed at rates suYcient <strong>to</strong> sustain life. Many of<br />

the reactions catalysed by enzymes are highly complex, yet they can be rationalised<br />

in terms of selective enzyme–substrate interactions <strong>and</strong> well-precedented<br />

chemical reactions. Could such selective catalysis be carried out by other<br />

biological macromolecules The answer is yes: we shall meet examples of<br />

naturally occurring ribonucleic acid (RNA) molecules capable of catalysing<br />

selective self-splicing reactions, <strong>and</strong> we shall see how the immune system can<br />

be used <strong>to</strong> produce catalytic antibodies.<br />

Finally, a challenging problem for the biological chemist is: if you think you<br />

underst<strong>and</strong> how enzymes work, can you design synthetic molecules capable of<br />

enzyme-like catalytic properties This is an exciting area of current research,<br />

<strong>and</strong> we shall see a few ingenious examples of how this problem has been<br />

addressed.<br />

12.2 Catalytic RNA<br />

Ribonucleic acid is an important cellular material involved in various aspects of<br />

protein biosynthesis. There are three types of RNA which are found in all cells:<br />

messenger RNA (mRNA) in<strong>to</strong> which the deoxyribonucleic acid (DNA) sequence<br />

of a gene is transcribed before being translated in<strong>to</strong> protein; transfer<br />

RNA (tRNA) which is used <strong>to</strong> activate amino acids for protein biosynthesis;<br />

<strong>and</strong> ribosomal RNA (rRNA) which comprises the ribosome protein assembly<br />

apparatus. Thus, information transfer <strong>and</strong> cellular structures were thought in<br />

the 1970s <strong>to</strong> be the only functions of RNA.<br />

In the early 1980s the groups of Cech <strong>and</strong> Altman reported the startling<br />

discovery that certain RNA molecules were capable of catalysing chemical<br />

reactions without the assistance of proteins. The Wrst catalytic RNA (or ‘ribozyme’)<br />

<strong>to</strong> be identiWed was found in the large sub-unit ribosomal RNA of a<br />

ciliated pro<strong>to</strong>zoan Tetrahymena thermophila. This RNA molecule has the remarkable<br />

ability <strong>to</strong> cut itself out of a larger piece of RNA, leaving a shortened<br />

RNA template which is subsequently used for protein biosynthesis. This<br />

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