CYL456: Chemistry of Life An Introduction

DNA as a hereditary material

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Translation
Instructor: Yashveer Singh, PhD
General, Organic, and Biological Chemistry, HS Stoker,
Brooks/Cole
Lehningers Principles of Biochemistry, DL Nelson and MM Cox,
WH Freeman
Molecular Cell Biology, H Lodish, A Berk, CA Kaiser, M Krieger,
MP Scott, A Bretscher, H Ploegh, P. Matsudaira, WH Freeman
16 October 2014

The genetic code

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Stokers General, Organic, and Biological Chemistry, 5 Ed.

The genetic code

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A codon is a three-nucleotide sequence in an mRNA molecule that codes for a

specific amino acid
Thus, there are 43 = 64 codons, which are more than enough combinations for
uniquely specifying each of the 20 standard amino acids found in proteins

The genetic code is the assignment of the 64 mRNA codons to specific amino
acids (or stop signals)
Marshall Nirenberg and Har Gobind Khorana were awarded Nobel Prize in
chemistry in 1968 for their work in illuminating how mRNA encodes for
proteins
(1) The genetic code is highly degenerate; that is, many amino acids are
designated by more than one codon

(2) The genetic code is almost universal

(3) An initiation and termination codon exists
Stokers General, Organic, and Biological Chemistry, 5 Ed.

Translation: protein synthesis

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Translation is the process by which mRNA codons are deciphered

and a particular protein molecule is synthesized
The substances needed for protein synthesis are mRNA molecules,
tRNA molecules, amino acids, ribosomes, and a number of
different enzymes

Stokers General, Organic, and Biological Chemistry, 5 Ed.

Ribosomes
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Ribosome: A ribosome is an rRNAprotein complex that serves as the

site for the protein synthesis. They contain four rRNA molecules and
about 80 proteins that are packed into two rRNA-protein subunits, one
small subunit and one large subunit
Each subunit contains approximately 65% rRNA and 35% protein by
mass

The ribosomes active site in the large ribosomal subunit

The mRNA involved in the translation phase of protein synthesis binds
to the small subunit
Stokers General, Organic, and Biological Chemistry, 5 Ed.

mRNA
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mRNA carried the genetic information stored in DNA to

cytoplasm in the form of genetic code. It binds to the ribosomes

evolutiondismantled.com

transfer RNA (tRNA)

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The t-RNA molecule have cloverleaf

shape, produced by its folding and
twisting into regions of parallel strands
and regions of hairpin loops
The 3- end of the open part of the
cloverleaf structure is where an amino
acid becomes covalently bonded to the
tRNA molecule through an ester bond
The loop opposite the open end of the
cloverleaf is the site for a sequence of
three bases called an anticodon. An
anticodon is a three-nucleotide sequence
on a tRNA molecule that is
complementary to a codon on an mRNA
molecule
Stokers General, Organic, and Biological Chemistry, 5 Ed.

transfer RNA (tRNA)

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Each of the different tRNA molecules is specifically recognized by an

aminoacyl tRNA synthetase enzyme. These enzymes also recognize
the one kind of amino acid that belongs with the particular tRNA
and facilitates its bonding to the tRNA
Stokers General, Organic, and Biological Chemistry, 5 Ed.

The three RNAs in translation

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Stokers General, Organic, and Biological Chemistry, 5 Ed.

Translation: activation of tRNA

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Two steps are involved in tRNA activation: an amino acid interacts

with an activator molecule (ATP) to form a highly energetic complex.
This complex then reacts with the appropriate tRNA molecule to
produce an activated tRNA molecule, a tRNA molecule that has an
amino acid covalently bonded to it at its 3- end through an ester
linkage
Stokers General, Organic, and Biological Chemistry, 5 Ed.

Translation: initiation
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The initiation begins with mRNA attaching itself to the surface of a small
ribosomal subunit such that its first codon (initiating codon AUG), occupies the site
called the P site (peptidyl site)
An activated tRNA molecule with anticodon complementary to the codon AUG
attaches itself to the AUG codon. The resulting complex then interacts with a large
ribosomal subunit to complete the formation of an initiation complex
Stokers General, Organic, and Biological Chemistry, 5 Ed.

Translation: elongation
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Next to the P site is a second binding site called the A site (aminoacyl site). At
this second site the next mRNA codon is exposed, and a tRNA with the appropriate
anticodon binds to it
With amino acids in place at both the P and the A sites, the enzyme peptidyl
transferase effects the formation of peptide bond. The empty tRNA at the P site
now leaves that site and is free to pick up another molecule of its specific amino
acid
Timberlakes General, Organic, and Biological Chemistry, 11 Ed.

Translation: elongation
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Simultaneously with the release of tRNA from the P site, the

ribosome shifts along the mRNA. This shift puts the newly formed
dipeptide at the P site, and the third codon of mRNA is now
available, at site A, to accept a tRNA molecule with complementary
anticodon
Timberlakes General, Organic, and Biological Chemistry, 11 Ed.

Translation: elongation
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The movement of a ribosome along an mRNA molecule is called

translocation

Timberlakes General, Organic, and Biological Chemistry, 11 Ed.

Acyl transfer reaction

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Stokers General, Organic, and Biological Chemistry, 5 Ed.

Translation: termination
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The polypeptide continues to grow until all necessary amino acids

are incorporated
Presence of one of the three stop codons (UAA, UAG, or UGA) in
mRNA will terminate the process. No tRNA has an anticodon that can
base-pair with these stop codons
The polypeptide is then cleaved from the tRNA by hydrolysis

Stokers General, Organic, and Biological Chemistry, 5 Ed.

Post translation processing

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In most proteins, the methionine (Met) residue that initiated protein

synthesis is removed by a specialized enzyme in a hydrolysis reaction. A
second hydrolysis reaction releases the polypeptide chain from its tRNA
carrier

Some covalent modification of a protein can occur, such as the

formation of disulfide bridges between cysteine residues
Completion of the folding of polypeptides into their active
conformations occurs. Protein folding actually begins as the polypeptide
chain is elongated on the ribosome
For protein with quaternary structure, the various components are
assembled together

Stokers General, Organic, and Biological Chemistry, 5 Ed.

Polyribosomes
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Many ribosomes move simultaneously along a single mRNA molecule. Thus,

many identical protein chains can be synthesized almost at the same time from a
single strand of mRNA
Such complexes of several ribosomes and mRNA are called polyribosomes or
polysomes
Stokers General, Organic, and Biological Chemistry, 5 Ed.