BioPHYSICAL chemistry

is how these early molecules gained the capacity for self-replication. In
organisms today, nucleic acids encode genetic information, which specifies
the synthesis of proteins, and proteins perform cellular reactions, including
the replication of nucleic acids. This interrelationship raises the question
of which came first, nucleic acids or proteins?
A possible answer came about with the discovery that some RNAs, termed
ribozymes, can have acatalytic role in the transcriptional processing of RNA;
this was recognized with the Nobel Prize for Chemistry to Thomas Cech
and Sidney Altman in 1989 (Guerrier-Takada & Altman 1984; Lantham
& Cech 1989). Most of the roles identified for ribozymes are based
upon splicing of RNA (Doudna & Cech 2002). In eukaroytic DNA, genes
are often divided into segments, termed exons, with intervening non-
coding regions termed introns. One prominent role of ribozymes is to
facilitate the splicing of the RNA to remove these noncoding regions.
To achieve this role, ribozymes have a wide range of sizes and structures.
The best-characterized ribozyme is RNase P, which promotes the self splic-
ing of a small RNA segment as part of replication. These RNA segments
are termed the hammerhead ribozyme as their structures are in the
shape of the head of a hammer (Figure 7.20). Other ribozymes are much
larger, with some containing over 400 nucleotides that form complex
structures. The ability of RNA molecules to act as catalysts in their
own formation suggests that RNA may have been both the first source
of genetic information and catalytic activity. According to this scenario,
the primitive Earth was an RNA world. One of the earliest stages of
evolution was the formation of RNA. As is true for protein enzymes, the
three-dimensional structure of ribozymes is critical in their ability to per-
form catalytic functions. Activity is lost when ribozymes are heated to
high denaturing temperatures or when essential nucleotides are changed.
The enhancement rate constant for ribozymes can be substantial; for
example, the self-cleaving hepatitis delta virus has a constant of about
103 s−^1. As found for their protein counterparts, ribozymes can make use
of cofactors, such as imidazole, and can be regulated by small-molecule
allosteric effects.

CHAPTER 7 KINETICS AND ENZYMES 159

Formation of

Earth

Stable

hydrosphere

Prebiotic

chemistry

Pre-RNA

world

RNA

world

First DNA/

protein life

Diversification

of life

4.5 4.2 4.2–4.0 ~4.0

Timescale (1000 million years)

~3.8 ~3.6 3.6 to present

Figure 7.19A timeline of events pertaining to the early history of the Earth. Modified from Joyce
(2002).