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Anatomy and Physiology I Protein Synthesis and the Genetic Code Instructor: Mary Holman Proteins • Every cell contains large numbers of diverse proteins • The proteins determine the physical and chemical characteristics of cells • Much of cellular machinery is devoted to synthesizing proteins • Instructions for making proteins are contained primarily in the DNA in the nucleus of the cell Organic Compounds Proteins • More complex than carbohydrates and lipids • Have a larger range of functions : structural material, energy source, hormones, receptors, enzymes, antibodies • Contain N as well as C, H, and O and some contain S • Amino acids are the building blocks (monomers) of proteins • There are twenty (20) different amino acids • Amino acids bind together by forming peptide bonds General structure of an amino acid R Fig. 2.17a H N C C H H O OH The portion common to all amino acids is within the oval. It includes the amino group (—NH2) and the carboxyl group (—COOH). The "R" group, or the "rest of the molecule," is what makes each amino acid unique. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 2.17b H C H C C H H C C H H S H C H C H N C C H H O OH (b) Cysteine. Cysteine has an R group that contains sulfur. H H C H N C C H H O OH Phenylalanine. Phenylalanine has a complex R group. Improper metabolism of phenylalanine occurs in the disease phenylketonuria. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 2.18 H N H A Peptide Bond H O C C R R N C H H O C (H2O) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. OH Primary Structure of Proteins Fig. 2.19a Amino acids Polypeptide chain Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Secondary Structure Tertiary Structure R H C H H C H Pleated structure C Coiled structure N H O H O N C N C C R C HO R N R C H R C H C N Three-dimensional folding Quaternary Structure R C H H R H N C H O C H C H H R C C N O O N C H C N H O C Two or more folded chains may connect and fold together Ex: Hemoglobin molecule Nucleic Acids • Huge molecules that contain C, H, O, N and P • Building blocks (monomers ) are nucleotides • Nucleic acids are of two varieties • Deoxyribonucleic acid (DNA) • Ribonucleic acid (RNA) Fig. 2.20 Basic Structure of a Nucleotide P Base Sugar Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 2.22 Different sugar groups of DNA and RNA O HOCH2 C H OH H H C C O HOCH2 C C H H H H C C OH Ribose OH H Deoxyribose Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. C H Nitrogenous Bases • The two types of nitrogenous bases in nucleotides: • Purines - structure of two joined organic rings • Pyrimidines - have a single organic ring Nitrogenous bases of DNA The Five Nitrogenous Bases DNA App. D Pg. 937 RNA App. D pg 937 The Molecular Structure of DNA Fig. 4.19a (a) Hydrogen bonds P P CC Fig. 4.19a Guanine (G) P TT CC GG P G C P A P Cytosine (C) P P Adenine (A) P P Thymine (T) P P DNA P G G C A Nucleotide strand Nucleotide strand G C T C G A Segment Segment of DNA of DNA molecule molecule Fig. 4.19b The Double Helix Structure of DNA Fig. 4.19b Globular histone proteins Chromatin Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.19c DNA as condensed Chromosome during Mitosis Metaphase chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig 4.20 (partial) DNA Replication prior to Mitosis A T C G Fig. 4.20b G C C G C Original DNA molecule G C G A C T G A T G C C Region of replication G A G C C C G G G T Newly formed DNA molecules C G G Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 2.21 P B P B P B P B P B P B S RNA B B B B B B P S P S P S P S S P B B S S S P B P S S P B S S S P B S S P B P S DNA Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. S P Fig. 4.21 RNA Differences from DNA S A P S U P S G P S G P S C P S A P S U P S U P S G P S U P • RNA is single stranded • contains ribose instead of deoxyribose • contains uracil instead of thymine • there are different types of RNA - all with unique roles Steps in Relaying the Genetic Information Stored in DNA to Proteins to be Synthesized • Transcription - in nucleus mRNA copies the DNA sequence • mRNA enters cytoplasm and arrives at a ribosome • Translation - on ribosome in cytoplasm tRNA matches its anticodon to codons on mRNA and delivers the corresponding amino acid. • The polypeptide chain of a new protein is assembled on the ribosome Fig. 4.22 Transcription by RNA from DNA bases DNA mRNA S P A U P Direction of “reading” code S S P T A P S S P G C P S S P C G P S S P G C S Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P Fig. 4.23a T Nucleus T A G C T A G C G T A G C A A C T G C T G T A C G T A G C A G C T A C T A T G C A T G C T A DNA strands pulled apart 2 A G C A Transcription Cytoplasm DNA double helix T A T G G G C T C C G C A A C G G C A G G C T C C A T G A C G T U 2 mRNA leaves the nucleus Messenger and attaches to a ribosome RNA A G C G C G C C G U A C G C G C G C G A T A T C G G C G C C G A T G C G C C G U A C G C G A T U A G C A T C G C Nuclear pore 1 DNA information is copied, or transcribed, into mRNA following complementary base pairing T A G DNA strand Messenger RNA C G C Transcription (in nucleus) G C C G A T G C C G C U C G A G 1 Fig 4.23b 3 Translation Fig. 4.23b Translation begins as tRNA anticodons recognize complementary mRNA codons, thus bringing the correct amino acids into position on the growing polypeptide chain leaves 2 mRNA the nucleus Amino acids attached to tRNA 6 Polypeptide chain and attaches to a ribosome 5 At the end of the mRNA, the ribosome releases the new protein Cytoplasm 4 tRNA molecules can pick up another molecule of the same amino acid and be reused As the ribosome moves along the mRNA, more amino acids are added Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.24a 1 1 2 Growing The transfer RNA molecule polypeptide for the last amino acid added chain holds the growing polypeptide Anticodon chain and is attached to its complementary codon on mRNA.A U G G G C U 1 2 3 4 Next amino acid 5 6 Transfer RNA U G C C G U C C G C A A C G G C A G G C A A G C G U 3 4 5 Codons Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6 7 Messenger RNA Fig. 4.24b Peptide bond 1 2 A second tRNA binds 2 complementarily to the Growing polypeptide next codon, and in doing chain so brings the next amino Anticodon acid into position on the ribosome. A U G G G C U A peptide bond forms, linking the new amino acid to the growing polypeptide chain. 1 2 3 4 Next amino acid 5 6 Transfer RNA U G C C G U C C G C A A C G G C A G G C A A G C G U 3 4 5 Codons Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6 7 Messenger RNA Fig. 4.24c 1 2 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. 3 4 7 5 Next amino acid 6 Transfer RNA 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 Ribosome Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Messenger RNA Fig. 4.24d Alanine Glycine Methionine Alanine Glycine Serine 1 2 4 3 A new tRNA complementary to the next codon on mRNA brings the next amino acid to be added to the growing polypeptide chain. 4 5 6 7 Next amino acid 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 1 2 3 4 5 6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7 Messenger RNA Step 1 Amino acids represented mRNA A U Fig. 4.23c Codon 1 Methionine G G G Codon 2 Glycine Codon 3 Serine Codon 4 Alanine Codon 5 Threonine Codon 6 Alanine Codon 7 Glycine C U C C G C A A C G G C A G G C Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.25 A single base Mutation Direction of “reading” code DNA Code for Glutamic acid P T DNA Mutation P S P P S A S C P S (a) T S T P Code for valine C S (b) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig. 4.26 STARTING MATERIALS Enzyme #1 Resulting Conditions INTERMEDIATE #1 Consequences of mutations in enzymes in the synthesis of Heme Enzyme #2 ALA dehydratase deficiency INTERMEDIATE #2 Enzyme #3 acute intermittent porphyria INTERMEDIATE #3 Enzyme #4 congenital erythropoietic porphyria INTERMEDIATE #4 Enzyme #5 porphyria cutanea tarda INTERMEDIATE #5 Enzyme #6 coproporphyria INTERMEDIATE #6 Enzyme #7 porphyria variegata INTERMEDIATE #7 Enzyme #8 HEME erythropoietic protoporphyria