UNURHORO EZEKIEL
14/MHS02/055
BCH 301
QUESTION
1. Discuss on the RNA serving as enzyme(Ribozyme)
2. Outline the metabolism pathway showing the biosynthesis of an essential amino
acid from 3-phosphorglycerol.
solution
Ribozymes (ribonucleic acid enzymes) are RNA molecules that are capable of catalyzing
specific biochemical reactions, similar to the action of protein enzymes. The 1982
discovery of ribozymes demonstrated that RNA can be both genetic material (like DNA)
and a biological catalyst (like protein enzymes), and contributed to the RNA world
hypothesis,which suggests that RNA may have been important in the evolution of
prebiotic self-replicating systems. The most common activities of natural or in vitroevolved ribozymes are the cleavage or ligation of RNA and DNA and peptide bond
formation. Within the ribosome, ribozymes function as part of the large subunit ribosomal
RNA to link amino acids during protein synthesis. They also participate in a variety of RNA
processing reactions, including RNA splicing, viral replication, and transfer
RNA biosynthesis. Examples of ribozymes include the hammerhead ribozyme, the VS
ribozyme, leadzyme and thehairpin enzyme.
Investigators studying the origin of life have produced ribozymes in the laboratory that
are capable of catalyzing there own sythnsis from activated monomers under very specific
conditions, such as an RNA polymerase ribozyme.[2] Mutagenesis and selection has been
performed resulting in isolation of improved variants of the "Round-18" polymerase
ribozyme from 2001. "B6.61" is able to add up to 20 Nucleotide to a primer template in
24 hours, until it decomposes by cleavage of its phosphodiester bonds. \ The "tC19Z"
ribozyme can add up to 95 Nucleotide with a fidelity of 0.0083 mutations/nucleotide.
Attempts have been made to develop ribozymes as therapeutic agents, as enzymes
which target defined RNA sequences for cleavage, as biosensors, and for applications
in functional genomic and gene discovery.
Structure and mechanism
Despite having only four choices for each monomer unit (nucleotides), compared to 20
amino acid side chains found in proteins, ribozymes have diverse structures and
mechanisms. In many cases they are able to mimic the mechanism used by their
protein counterparts. For example, in self cleaving ribozyme RNAs, an in-line SN2
reaction is carried out using the 2’ hydroxyl group as a nucleophile attacking the
bridging phosphate and causing 5’ oxygen of the N+1 base to act as a leaving group. In
comparison, RNase A, a protein that catalyzes the same reaction, uses a coordinating
histidine and lysine to act as a base to attack the phosphate backbone.
Like many protein enzymes metal binding is also critical to the function of many
ribozymes. Often these interactions use both the phosphate backbone and the base of
the nucleotide, causing drastic conformational changes.
Image showing the diversity of ribozyme structures. From left to right: leadzyme, hammerhead
ribozyme, twister ribozyme
THE APPLICATION OF RIBOZYME (RNA)
Ribozymes have been proposed and developed
1, for the treatment of disease through gene therapy (3). One major challenge of using
RNA based enzymes as a therapeutic is the short half-life of the catalytic RNA
molecules in the body. A type of synthetic ribozyme directed against HIV RNA called
gene shears has been developed and has entered clinical testing for HIV infection.
2, a ribozyme has been designed to target the hepatitis C virus RNA. The ribozyme is
able to cleave the conserved regions of the virus’s genome which has been shown to
reduce the virus in mammalian cell culture.[23] Despite these efforts by researchers,
these projects have remained in the preclinical stage.
SOLUTION TO QUESTION 2
Serine as a named amino acid.
Serine is the first amino acid in this family to be produced; it is then
modified to produce both glycine and cysteine (and many other biologically
important molecules). Serine is formed from 3-phosphoglycerate in the
following pathway:
3-phosphoglycerate-> phosphohydroxyl-pyruvate-> phosphoserine-> serine
The conversion from 3-phosphoglycerate to phosphohydroxyl-pyruvate is
achieved by the enzyme phosphoglycerate dehydrogenase. This enzyme is
the key regulatory step in this pathway. Phosphoglycerate dehydrogenase
is regulated by the concentration of serine in the cell. At high
concentrations this enzyme will be inactive and serine will not be produced.
At low concentrations of serine the enzyme will be fully active and serine
will be produced by the bacterium.] Since serine is the first amino acid
produced in this family both glycine and cysteine will be regulated by the
available concentration of serine in the cell.
THE END