Cellular Metabolism Chapter 4 Copyright  The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Genetic Code Specification of the correct sequence of amino acids in a polypeptide chain Each amino acid is represented by a triplet code of DNA bases The base sequence of a gene then determines the amino acid sequence in a polypeptide Since DNA stays in the nucleus, and proteins are made in the cytoplasm, DNA’s code must be copied and carried to the cytoplasm. RNA molecules accomplish this transfer of the genetic code.

RNA Molecules Single strand of nucleotides Each nucleotide contains: ribose, phosphate, base (A, G, C, and Uracil instead of Thymine) Shorter than DNA Different types: mRNA (carries code from DNA to ribosome), tRNA (brings amino acids to ribosome), rRNA (a component of ribosomes)

Protein Synthesis Protein Synthesis involves 2 steps, each requiring RNA and enzymes Transcription occurs in the nucleus and is the process of copying DNA information into an RNA sequence Translation occurs at the ribosomes in the cytoplasm as the code is transferred to a growing chain of amino acids

Animation: Stages of Transcription Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer.

Transcription of Messenger RNA (mRNA) Occurs in nucleus A section of DNA opens up (just where the gene coding for the particular protein is) mRNA nucleotides pair up with the DNA bases on one side---uracil is used instead of thymine mRNA moves away and DNA closes up Controlled by RNA polymerase Post-Transcription Once the mRNA has gone through splicing, capping, and tailing it goes through nuclear pore and attaches to a ribosome in the cytoplasm. DNA RNA S P A U P S S P T A P S S P Direction of “reading” code G C P S S P C G P S S P G C P S

Animation: How Translation Works Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer.

Translation Occurs in cytoplasm Ribosome attaches to mRNA Each tRNA molecule has an attachment point for a specific amino acid Each tRNA also has a region of 3 bases called an anticodon which is attracted to complementary mRNA codons Once a ribosome finds the start codon (AUG) it moves down the mRNA strand, tRNA’s bringing their amino acids are attracted to the mRNA codons and a peptide bond is formed and the tRNA is released Process continues until a stop codon (UAA, UAG, UGA) is reached and then the polypeptide is released

Post -Translation Modifications to create a mature protein with the proper conformation and function Phosphorylation – addition of phosphate groups Cleavage – removal of certain amino acids Glycosylation- the addition of carbohydrate chains on amino acids Lipidation – the attachment of lipid molecules on amino acids (especially for proteins destined for cell membranes) Formation of disulfide bridges from cysteine residues

Translation

Protein Synthesis Cytoplasm 3 Translation begins as tRNA anticodons recognize complementary mRNA codons, thus bringing the correct amino acids into position on the growing polypeptide chain DNA double helix Amino acids attached to tRNA Nucleus T A T A 6 tRNA molecules can pick up another molecule of the same amino acid and be reused G C G C 2 mRNA leaves the nucleus and attaches to a ribosome A T A T Polypeptide chain Messenger RNA G C DNA strands pulled apart A T A T T U A C G G G C T A G G C G G C C C G 5 At the end of the mRNA, the ribosome releases the new protein C G T U A T A C C G G C C C G A T G C G C C G A A T G C A A T Nuclear pore 4 As the ribosome moves along the mRNA, more amino acids are added Amino acids represented A T C C G C G G G C T A G G C 1 DNA information is copied, or transcribed, into mRNA following complementary base pairing A C C G U Codon 1 Methionine A A T C G G G C G T A G G C G C C G G Codon 2 Glycine G C A T T U A C C C G C C G U G C A A T C Codon 3 Serine A T T U A C C G G G C Messenger RNA DNA strand G T A A A T C C G C Codon 4 Alanine G C A C G G C A T A C G C Codon 5 Threonine G C A T G Transcription (in nucleus) G C Translation (in cytoplasm) G G C C Codon 6 Alanine C G A U A G C G G Codon 7 Glycine C

Protein Synthesis 1 2 1 The transfer RNA molecule for the last amino acid added holds the growing polypeptide chain and is attached to its complementary codon on mRNA. Growing polypeptide chain 3 4 Next amino acid 5 6 Transfer RNA Anticodon U G C C G U A U G G G C U C C G C A A C G G C A G G C A A G C G U 1 2 3 4 5 6 7 Codons 1 Peptide bond 2 2 A second tRNA binds complementarily to the next codon, and in doing so brings the next amino acid into position on the ribosome. A peptide bond forms, linking the new amino acid to the growing polypeptide chain. Growing polypeptide chain 3 4 Next amino acid 5 6 Transfer RNA Anticodon U G C C G U A U G G G C U C C G C A A C G G C A G G C A A G C G U Messenger RNA 1 2 3 4 5 6 7 Codons 1 2 Next amino acid 3 The tRNA molecule that brought the last amino acid to the ribosome is released to the cytoplasm, and will be used again. The ribosome moves to a new position at the next codon on mRNA. A 3 4 5 7 6 Transfer RNA U G C C C G C G U A U G G G C U C C G C A A C G G C A G G C A A G C G U Messenger RNA 1 2 3 4 5 6 7 Ribosome 1 2 4 A new tRNA complementary to the next codon on mRNA brings the next amino acid to be added to the growing polypeptide chain. 3 4 5 Next amino acid 6 7 Transfer RNA C G U C C G A U G G G C U C C G C A A C G G C A G G C A A G C G U Messenger RNA 1 2 3 4 5 6 7

Animation: Protein Synthesis Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer.

Changes in Genetic Information Only about 1/10th of one percent of the human genome differs from person to person Nature of Mutations Mutations – change in genetic information Result when: Extra bases are added or deleted Bases are changed Code for glutamic acid Mutation Code for valine P P T T S S Direction of “reading” code P P T A S S May or may not change the protein P P C C S S (a) (b)

Protection Against Mutation Repair enzymes correct the mutations Inborn Errors of Metabolism Occurs from inheriting a mutation that then alters an enzyme This creates a block in an otherwise normal biochemical pathway