BIOCHEMISTRY MEDICAL

1. Protein Synthesis in Cell

2. Learning Objectives
• Importance of proteins
• Site of protein synthesis
• Steps of protein synthesis
• Regulation of protein synthesis
• Applied aspects
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3. Proteins: their importance
• Membrane proteins
• Structural proteins
• Enzymes
• Hormones
• Antigens
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4. 10/18/2015 Dept. of Physiology, MSRMC
Site of Protein Synthesis

5. Site of Protein Synthesis
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6. DNA
• DNA has two functions.
– self-renewing data repository that maintains a
constant source of genetic information for the
cell.
– serve as a template for the translation of
genetic information into proteins, which are
the functional units of the cell.
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7. Basic building blocks of DNA
• Phosphoric acid
• Sugar
• Nitrogenous base
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8. Genetic Code
• The gene consists of a segment of DNA that
is transcribed into RNA.
• The genetic code consists of successive
"triplets" of bases on the DNA.
• Each three successive bases is a code word.
• The successive triplets eventually control the
sequence of amino acids in a protein
molecule that is to be synthesized in the cell.
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9. Pathway from Genes to Proteins
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10. • Central dogma of molecular biology:
genetic information flows unidirectionally
from DNA to proteins.
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11. Steps of Protein Synthesis
• Transcription
• Translation
• Post translational modificaton
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12. Transcription
• Definition: Transcription is the synthesis
of RNA from a DNA template, mediated by
an enzyme called RNA polymerase.
• Site: Nucleus
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13. • Requirements:
– DNA template
– RNA polymerase
– Activated ribonucleotides
Transcription contd.
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14. Building blocks of RNA
• Phosphoric acid
• Sugar
• Nitrogenous base
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15. • The basic building blocks of RNA form
RNA nucleotides.
• RNA nucleotides are then activated by
RNA Polymerase.
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16. • RNA polymerase recognises the promoter
region in DNA and binds to it.
• Unwinding of a segment of DNA
• Attachment of activated ribonucleotides to
the DNA segment
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17. • Polymerase moves along the DNA strand
• Breakage of 2 phosphate radicals from
RNA nucleotides
• Covalent linkage of 3rd phosphate with
ribose
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18. • RNA polymerase reaches end of DNA
gene (chain terminating sequence)
• Breaking away of polymerase & RNA
chain
• Formation of RNA transcript
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19. • The code that is present in the DNA strand
is eventually transmitted in complementary
form to the RNA chain.
• The ribose nucleotide bases always
combine with the deoxyribose bases in a
fixed combination.
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20. DNA Base RNA Base
Guanine…………………………….……Cytosine
Cytosine ………………………..…….… Guanine
Adenine …………………………………… Uracil
Thymine ………………………………… Adenine
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22. • The RNA that is initially transcribed from a
gene is called the primary transcript.
• Most eukaryotic genes contain exons,
DNA sequences that are present in the
mature mRNA, alternating with introns,
which are not present in the mRNA.
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23. • Splicing
• Addition of 5’ methyl cap
• Cleavage of RNA transcript downstream
from polyadenylation signal
• Addition of poly A tail
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Processing of The Primary
Transcript

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25. Types of RNA
• mRNA
• tRNA
• rRNA
• miRNA
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26. mRNA
• mRNA molecules are long, single RNA
strands that are suspended in the
cytoplasm.
• They contain codons that are exactly
complementary to the code triplets of the
DNA genes.
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27. • Carrier for specific amino acids from
cytoplasm to mRNA
• Has sites for binding amino acid & mRNA
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tRNA

28. rRNA
• Functions in association with tRNA &
mRNA
• Present in ribosomes
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29. miRNA
• Non-coding RNA
• Regulate gene expression
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30. Translation
• Definition: Translation is the synthesis
of protein from RNA.
• Site: Ribosomes
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31. • Requirements:
– Amino acids
– mRNA
– tRNA
– ATP
Translation contd.
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32. • Begins at AUG
• Ends at UAG, UAA, UGA
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Translation contd.

33. • Amino acid + ATP
• Activated amino acid + AMP
• tRNA
• Amino acid tRNA complex
• Binds to mRNA
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34. • Peptide bonds formed between
successive amino acids
• Process stops at chain termination codon
• Release of polypeptide
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Translation contd.

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36. • It is common to have more than one
ribosome on a given mRNA chain at a
time.
• The mRNA chain plus its collection of
ribosomes is visible under the electron
microscope as an aggregation of
ribosomes called a polyribosome.
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37. 10/18/2015 Dept. of Physiology, MSRMC

38. Post-translational Modification
• Folding
• Hydroxylation
• Carboxylation
• Glycosylation
• Phosphorylation
• Cleavage of peptide bonds
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39. Regulation of Gene Expression
• Step 1: Chromatin remodeling
• Step 2: Initiation of transcription
• Step 3: Transcript elongation
• Step 4: Termination of transcription
• Step 5: RNA processing
• Step 6: Nucleocytoplasmic transport
• Step 7: Translation
• Step 8: mRNA degradation
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41. Applied physiology
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42. Mutation
• Definition: change in the DNA structure of
a gene
• Types:
– Point mutation (transition, transversion)
– Frame shift mutation(deletion, insertion)
• Mutations can lead to genetic diseases,
cancers.
• Some mutations may be silent.
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43. Genetic diseases
• Sickle cell anaemia
• Cystic fibrosis
• Phenylketonuria
• Huntington’s chorea
• Haemophilia
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44. • Gene therapy: methods to cure an
inherited disease by providing a patient
with correct copy of a defective gene.
• Gene therapy has been successful in
– Cystic fibrosis
– Severe combined immunodeficiency
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Gene therapy

45. Summary
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