Transcript The Biochemical Basis of life

The Biochemical
Basis of Life
(Two Lectures)
By
Prof. Dr. Zainalabideen A Abdulla,
DTM&H., MRCPI, Ph.D., FRCPath. (U.K.)
Second Lecture
IV. Nucleic Acids
Function
- DNA and RNA
- Contain: C, H, O, N, and P
- DNA: • “Hereditary Molecule”: Genes & genetic code
• Major portion of chromosomes
- RNA: Flow of information from DNA to cell
Structure of nucleic acids
DNA and RNA Nucleotides
• Building blocks of nucleic acid polymers
(repeated monomers)
• Three subunits:
1. Nitrogen-containing (nitrogenous) base
A (Adenine), G (Guanine), C (Cytosine)
T (Thymine; DNA), U (Uracil; RNA)
cont./…
cont./…DNA and RNA Nucleotides
2. Pentose (5-carbon sugar)
- Deoxyribose: For DNA
- Ribose: For RNA
3. Phosphate group
• A & G: Purines (2 rings)
• C, T, U = Pyrimidines (1 ring)
Types of RNA
1. Messenger RNA (mRNA)
2. Ribosomal RNA (rRNA)
3. Transfer RNA (tRNA)
Polymers: Formed from >100,000 monomers by
joining the nucleotides via covalent bonds via rRNA
(between their sugar and phosphate groups)
- The bonding force of the double stranded polymer
Double α-helix (right-handed staircase)
DNA replication
- DNA replication: DNA in chromosomes duplicate
- Separation of DNA strands
- Building of complementary strands by the addition of
the correct DNA nucleotides
- Replication fork: Point where DNA replication starts
- Daughter cells: Same number of chromosomes,
same genes and same DNA amount
cont./…DNA replication
- DNA polymerase (DNA-dependent DNA
polymerase): The enzyme required for replication
- Other enzymes:
• DNA helicase/Topoisomerase: Separation
• Primase: Synthesizes short RNA primer
• DNA ligase: Connect fragments of new DNA
Gene expression
- Gene: A particular segment of a DNA molecule or
chromosome
- Gene contains: “Recipe” or “blueprint” to make a
“gene product”; may be >1
- Genetic code: “A”, “G”, “C”, “T”:
• Spell the code
• Instruction for production of:
- Particular protein
- rRNA, tRNA
The Central Dogma (Francis Crick, 1957):
DNA
mRNA
Protein
(flow of genetic information within the cell)
- “One gene - one protein hypothesis”
- Gene in action: “Expressed”:
• Continuously: Constitutive genes
• On need: Inducible genes
- Dogma = means “Basic”, “fundamental”
Transcription
Need to produce a particular protein
DNA of a particular gene activated
(unwind temporarily)
Expose bases
Attract bases of free RNA nucleotides
(mRNA assembled along one DNA strand= DNA Template)
mRNA released to cytoplasm to direct protein synthesis
cont./… Transcription
- RNA polymerase (DNA-dependent RNA polymerase):
Primary enzyme of transcription
- “Traffic signals”: Nucleotide sequences of DNA
template (start & stop points for each gene) guiding
RNA polymerase start and stop
- Transcription in Eukaryotes: In the Nucleus
travel
to cytoplasm/to ribosomes (“protein assembly line”;
composed of protein + rRNA; attached to rough ER)
• Prokaryotes: In cytoplasm
Translation (Protein synthesis)
- mRNA base sequence: Interpreted (read) in groups of
3 bases (codons); amino-acid
insertion, start and stop points
- Amino acids activated by attaching to proper tRNA via
amino acyl-tRNA synthetase
carried to ribosomes
- tRNA contains anticodon (three base sequence)
complementary to codon of mRNA (e.g. tRNA: UUU =
mRNA AAA). This process is Translation= protein
synthesis
mRNA and tRNA
- mRNA constantly produced in the nucleus
- Both are short-lived, but re-used
- tRNA: Made in nucleolus
- Ribosomes lasts longer than mRNA
- tRNA attaches mRNA while sliding over ribosome
- tRNA bring the correct amino acids
polypeptides
formed
take the shape
determine function
cont./…mRNA and tRNA
- If one base is incorrect (mutation): Sequence/shape
differ/ function altered; disease results, Examples:
• Sickle cell anemia
• Cystic fibrosis
• Albinism
- Similarly: Non-pathogenic bacteria mutate to be
pathogenic or vice versa
- Genetic engineering and gene therapy are used for
preparation of medicine/vaccines and repair of genetic
damages respectively
Francis Crick
&
James Watson