Nucleic Acids and Protein Synthesis

Nucleic Acids and Protein Synthesis
Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.
1. Introduction DNA is a biological polymer composed of two molecular strands held together by hydrogen bonds. RNA DNA -Nucleic acids carry genetic information in cells DNA – deoxyribonucleic acids (2 deoxyribose) RNA – Ribonucleic acids (ribose) -DNA has two strands, twisted ladder (α helix), is antiparallel backbone of alternating sugar and phosphate units and rungs made of hydrogen-bonded pairs of heterocyclic amine bases Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

1. Introduction 23 pairs of chromosomes 30,000 to 35,000 genes One gene – one protein Chromosome 19 (to the right) Four Nitrogenous Bases Adenine Cytosine Thymine (Uracil in RNA) Guanine Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Nucleotides Mild degradations of Nucleic Acids yield monomeric units called Nucleotides. General formula for a nucleotide and the specific structure of one called adenylic acid: Complete hydrolysis of a nucleotide furnishes: 1. A heterocyclic base from either the purine or pyrimidine family. 2. A five-carbon monosaccharide that is either D-ribose or 2-deoxy-D-ribose. 3. A phosphate ion. AMP Adenosine Mono Phosphate Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Nucleosides Nucleosides are glycosylamines in which the amino component is a pyrimidine or a purine and in which the sugar component is either D-ribose or 2-deoxy-D-ribose (i.e., D-ribose minus the oxygen at the 2 position). Nucleosides are the important components of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid). Nucleosides 9 9 1 1 Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

2. Nucleotides and Nucleosides Nucleotide hydrolysis yields one of four heterocycles, one of two pentoses, and phosphate. Nucleoside hydrolysis yields heterocyclic base, and pentose. Uracil replaces Thymine in an RNA nucleoside Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

2. Nucleotides and Nucleosides Practice Problem 25.1 Write the structures of other tautomeric forms of adenine, guanine, cytosine, thymine, and uracil Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

3. Laboratory Synthesis of Nucleosides and Nucleotides -One technique uses reaction that assemble the nucleoside from suitably activated and protected ribose derivatives and heterocyclic base. -Another technique involves formation of the heterocyclic base on a protected ribosylamine derivative. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

3. Laboratory Synthesis of Nucleosides and Nucleotides The third technique involves the synthesis of a nucleosides with a substituent in the heterocyclic ring that can be replaced with other groups. A chlorinated heterocyclic nucleoside can be modified. R Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

3. Laboratory Synthesis of Nucleosides and Nucleotides Specific phosphorylation (selectively) of the 5’-OH can be achieved if the 2’- and 3’-OH groups of the nucleoside are protected by an isopropylidene group. - A nucleoside is converted to a nucleotide. 5’ 3’ 2’ Isopropylidene - Mild acid-catalyzed hydrolysis removes the acetonide group, and hydrogenolysis cleaves the benzyl phosphate bonds. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

(a)The isopropylidene group is part of a cyclic acetal and is thus susceptible to hydrolysis by mild acid. (b)It can be installed by treating the nucleoside with acetone and a trace of acid and by simultaneously removing the water that is produced. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

3. Laboratory Synthesis of Nucleosides and Nucleotides 3A. Medical Applications 6-Mercaptopurine is used to treat acute leukemia. Allopurinol is used to treat gout. Acyclovir is used to treat herpes virus. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Deoxyribonucleic acid
O-P-O-P-O-P-OCH2 1’ 2’ 3’ 4’ 5’ N o NH2 O - H OH DNA is a nucleotide polymer linked by a 3’ to 5’ phosphodiester bond 5’ phosphate H OH OCH2 1’ 2’ 3’ 4’ Nitrogenous base O - -P 5’ 3’ hydroxyl Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

4. Deoxyribonucleic Acid: DNA 4A. Primary Structure -The connecting links in proteins are amide groups; in nucleic acids they are phosphate ester linkages. -Phosphate esters link the 3’-OH of one ribose (or deoxyribose) with the 5’-OH of another. This makes the nucleic acid a long unbranched chain with -We would indicate the direction of the bases in Figure in the following way: -The base sequence along the chain of DNA that contains the encoded genetic information. -The sequence of bases can be determined using enzymatic methods and chromatography. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

varies from species to species Chargaff’s Rules: Total Mole Percentage (%G + %A) (%C + %T) %A/%T % G/%C This ratio is characteristic of the DNA of a given species, it is the same for DNA obtained from different tissues of the same animal and does not vary appreciably with the age or conditions of growth of individual organisms within the same species Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Prepared by Dr. Khalid Shadid
4. Deoxyribonucleic Acid: DNA Adenine Thymine (A-T) 2 H Bonds Cytosine Guanine (C-G) 3 H Bonds Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

A model for Secondary structure of DNA given by Watson and Crick in 1953 Watson and Crick proposed a double helix as a model for the secondary structure of DNA This work earned Crick, Watson, and Wilkins the Nobel Prize in Physiology or Medicine Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Why a helix? Why not a ladder?
A side view of base pairs shows they are perpendicular to the helix axis The heterocyclic bases have flat surfaces which are hydrophobic To exclude water from between the rings, we should bring the bases closer together One way to model them closer together is to “twist” the ladder into a helix Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

What holds DNA together?
Sugar-phosphate backbone outside (1) minimizes electrostatic repulsion, (2) interacts with water Bases inside (3) hydrogen-bonded (4) plus base stacking by hydrophobic interactions Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Picture of E. coli DNA outside of the cell
Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

DNA Packaging Human DNA total length is ~2 meters Is packaged into a nucleus that is ~ 5 microns in diameter This represents a compression of more than 100,000 fold It is made possible by wrapping the DNA around protein spools called nucleosomes and then packing these into helical filaments Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

4. Deoxyribonucleic Acid: DNA Replication of DNA Replication is the process of making a new DNA molecule from an existing DNA molecule that is identical to the original molecule. This process takes place during INTERPHASE This process is necessary to produce another molecule exactly the same as itself to ensure that the genetic code is passed on to each new daughter cell formed during cell division. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

How does replication take place?
The process is catalysed by the enzyme DNA polymerase The double helix unwinds The weak hydrogen bonds holding the base pairs together break, allowing the two strands to part Each single chain of bases is exposed Free nucleotides in the cytoplasm become attached to their matching, exposed base partners The two daughter DNA molecules each twist to form a double helix which then winds itself around the histones (proteins), forming a chromosome. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

Prepared by Dr. Khalid Shadid
BASE PAIRING RULE A always pairs with T and G always pairs with C If one half of DNA has a base sequence of: T A C C T G A T G T C A A G What is the base sequence of the other half? Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

The Central Dogma of Molecular Genetics

RNA and Protein Synthesis
Types of RNA mRNA rRNA tRNA Different to DNA in that: Consists of a single strand Is much shorter Sugar is ribose, not deoxyribose Contains Uracil, not Thymine

RNA and Protein Synthesis
First process: takes place in the cell nucleus, and the second in the cytoplasm. The first is Transcription, a process in which the genetic messenger is transcribed on to a form of RNA, called Messenger RNA(mRNA). The second process involves two other forms of RNA, called Ribosomal RNA(rRNA) and Transfer RNA (tRNA). -Messenger mRNA carries coded instructions for protein synthesis -Transfer tRNA carries specific amino acids to ribosomes during protein assembly -Ribosomal rRNA part of ribosomes

5A. Messenger RNA Synthesis – Transcription
DNA – Template mRNA – product RNA Polymerase

5. RNA and Protein Synthesis
Transcription Transcription is catalyzed by the enzyme RNA polymerase The process occurs in three stages. 1. Initiation: Involves binding of RNA polymerase to a specific nucleotide sequence, the promoter, at the beginning of a gene. This interaction of RNA polymerase with specific promoter DNA sequences allows RNA polymerase to recognize the start point for transcription. It also determines which DNA strand will be transcribed. Unlike DNA replication, transcription produces a complementary copy of only one of the two strands of DNA. As it binds to the DNA, RNA polymerase separates the two strands of DNA so that it can “read” the base sequence of the DNA.

Transcription 2. Chain elongation: begins as the RNA polymerase “reads” the DNA template strand and catalyzes the polymerization of a complementary RNA copy. With each step, RNA polymerase transfers a complementary ribonucleotide to the end of the growing RNA chain and catalyzes the formation of a 3’–5’ phosphodiester bond between the 5’ phosphoryl group of the incoming ribonucleotide and the 3’ hydroxyl group of the last ribonucleotide of the growing RNA chain. 3. Termination: The RNA polymerase finds a termination sequence at the end of the gene and releases the newly formed RNA molecule.

Translation The genetic code in DNA is carried as a sequence of ‘code-words’ on the mRNA. Each codeword is made up of three bases called a codon and each codon codes for a single amino acid. Each amino acid, therefore, has a different code of three letters. The order of the codons in mRNA will therefore determine the sequence of the amino acids which, in turn, determines which protein is formed. A gene is made up of a group of codons that code for the synthesis of one protein. (Smallest protein = 50 amino acids)

Translation A tRNA picks up a specific amino acid from the cytoplasm and transfers it to a ribosome.( # 20 - tRNA) The anticodon bases link up to their complementary bases of the codon. THIS IS CALLED TRANSLATION. Catalysed by enzymes, the amino acids link together by means of peptide bonds and the tRNA molecule is released to carry more of its specific amino acids to the ribosome. In this way the amino acids are linked up to form a specific protein in an order corresponding to the sequence of codons in the mRNA, which, in turn, was coded by the DNA.

© 2014 by John Wiley & Sons, Inc. All rights reserved.
5. RNA and Protein Synthesis 5D. The Genetic Code DNA is transcribed to an antisense DNA. Antisense DNA is transcribed to mRNA. DNA code = mRNA code mRNA is translated to Amino Acids / Protein. © 2014 by John Wiley & Sons, Inc. All rights reserved.

Nucleic Acids and Protein Synthesis

Similar presentations

Presentation on theme: "Nucleic Acids and Protein Synthesis"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Nucleic Acids and Protein Synthesis

Similar presentations

Presentation on theme: "Nucleic Acids and Protein Synthesis"— Presentation transcript:

Similar presentations

About project

Feedback