Chapter 4 Metabolism Anatomy & Physiology ivyanatomy.com

Cellular Metabolism Metabolism is the sum of all reactions in the body Anabolism Catabolism Synthesize larger molecules from smaller ones. Cells use energy Decomposes larger molecules into smaller ones. Releases energy for cellular use

Anabolic Reactions Dehydration Synthesis A water molecule is released to join molecules together. Most polymers are synthesized through dehydration synthesis. H2O + + Glucose molecules are joined by dehydration synthesis

Dehydration Synthesis Dehydration synthesis synthesizes polysaccharides, fats, proteins, and nucleic acids from their monomers. Several Monomers Polymer H2O +

Dehydration Synthesis Dehydration synthesis of a polysaccharide. H2O + glucose Amylose is a polysaccharide composed of several thousand glucose monosaccharides.

Dehydration Synthesis Dehydration synthesis of a triglyceride. + 1 glycerol + 3 fatty acid molecules triglyceride H2O

Dehydration Synthesis Dehydration synthesis of a polypeptide. amino acid + amino acid dipeptide + H2O

Dehydration Synthesis Dehydration synthesis of a polynucleotide. P O OH P O OH CH2 CH2 S B S B S CH2 B P O OH S CH2 B P O OH OH + H2O

Hydrolysis Water is consumed to break apart the molecules hydrolysis is the reverse of dehydration synthesis hydrolysis releases energy from chemical bonds H2O + +

Hydrolysis Hydrolysis is used to decompose polysaccharides, fats, proteins, and nucleic acids into their monomers. Polymer Several Monomers + H2O

Hydrolysis + H2O Hydrolysis of a polysaccharide. glucose Water is added to amylose, which decomposes into glucose molecules

Hydrolysis Hydrolysis of a triglyceride (fat). + H2O +

Hydrolysis + + H2O Hydrolysis of a dipeptide. amino acid + amino acid

Hydrolysis + S S S S B H2O B B B Hydrolysis of a dinucleotide. P O OH CH2 S B Nucleotide + Nucleotide S CH2 B P O OH S CH2 B P O OH S CH2 B P O OH H2O +

Dehydration Synthesis + Monomers linked by covalent bond Hydrolysis + Monomers linked by covalent bond

Activation energy Activation Energy – Amount of energy required to initiate a reaction

Activation energy A catalyst – increases the rate of the reaction without being consumed by the reaction Activation energy without catalyst Activation energy with a catalyst Catalysts lower the activation energy required to initiate a reaction Lower energy state

Enzymes Characteristics of enzymes Enzymes lower the activation energy of a reaction Most enzymes are proteins Enzymes catalyze reactions (they increase the rate of reactions, but are not consumed by the reaction) Enzymes are specific to one substrate*. Most enzymes end in ____ase. (lipase, protease, nuclease, ATPase, etc.) *A substrate is the target molecule of an enzyme

Proteins Enzymes catalyze reactions (increases rate), but are not consumed by the reaction (reusable). Substrates Product A B A B A B A B Active Site Active Site Active Site Active Site Enzyme Enzyme-Substrate Complex Enzyme is unchanged Synthesis reaction involving an enzyme

Enzymes The rate of an enzyme-catalyzed reaction is limited by: 1. The concentration of substrate 2. The concentration of enzyme 3. Enzyme efficiency Measures how efficiently the enzyme converts substrates into produces

Metabolic Pathways A metabolic pathway is a complex series of reactions leading to a product Metabolic Pathways are controlled by several enzymes

Metabolic Pathways Enzyme A = Rate-limiting Enzyme The product of each reaction becomes the substrate of next reaction. Each step requires its own enzyme The least efficient enzyme is the “Rate-Limiting Enzyme” Rate-limiting enzyme is usually first in sequence Substrate 1 2 Enzyme B Enzyme A 3 Enzyme C 4 Enzyme D Product Enzyme A = Rate-limiting Enzyme

Negative Feedback in Metabolic Pathway In some pathways the product inhibits the enzymes through negative feedback inhibition. Negative feedback regulates the amount of product being produced. Substrate 1 2 Enzyme B Enzyme A 3 Enzyme C 4 Enzyme D Product Rate-limiting

Enzymes Cofactor substance that increases the efficiency of an enzyme Cofactors include ions (zinc, iron, copper) and coenzymes Coenzymes are organic cofactors Coenzymes include Vitamins (Vitamin A, B, D) Reusable – required in small amounts

Enzymes Vitamins are essential organic molecules that humans cannot synthesize, so they must come from diet Many vitamins are coenzymes Vitamins can function repeatedly, so can be used in small amounts. Example: Coenzyme A

Energy Energy: is the capacity to change something, or ability to do work. Common forms of energy: Heat Radiant (light) Sound Chemical Mechanical Electrical

Energy Conservation of Energy: Energy can be converted from one form to another, but it cannot be created or destroyed.

Energy Examples of transferring energy: Automobile energy converts chemical energy into mechanical and heat energy Lightbulb converts electrical energy into radiant (light) energy and heat energy Tree converts radiant (light) energy from the sun into chemical energy.

ATP Molecules ATP P ATP (Adenosine Triphosphate) carries energy in a form the cell can use currency of energy in a cell. adenine ribose P Adenosine Triphosphate ATP

Hydrolysis of ATP Cells obtain energy by hydrolyzing the third phosphate of ATP, releasing energy stored in the chemical bond.

ATP Cells have a limited supply of ATP, so they must continually regenerate ATP supplies through cell respiration. ATP is similar to cash. Cells have a limited supply and when it’s gone, it’s gone.

ATP = Energy currency for cells Cellular Respiration Cell Respiration: transfers the energy from food molecules into a form the cells can use (ATP). Energy from foods such as glucose is used to make ATP for the cell. 36 – 38 ATPs Initial fuel or energy source ATP = Energy currency for cells Reaction depicting the aerobic respiration of 1 glucose molecule into energy for 36 – 38 ATPs

Cell respiration replenishes ATP supplies. Energy invested from respiration Cell respiration replenishes ATP supplies. + Energy released for metabolism Normal cell activities deplete ATP supplies.

Overview of Cell Respiration Oxidation – transfer of electrons to a final electron acceptor, such as oxygen. Oxidation releases energy from glucose + + Glucose (C6H12O6) 6 O2 6 CO2 6 H2O + +

Release of Chemical Energy Oxidation of glucose releases energy that is use to produce new ATP C6H12O6 (Glucose) 6 CO2 + 6 O2 6 H2O Energy + + Energy is transferred to ATP: 40% is captured to produce ATP 60% is released as heat

Overview of Cell Respiration oxygen present (aerobic respiration) 2. Citric Acid Cycle 3. Electron Transport Chain 1. Glycolysis Glucose (C6H12O6) Lactic Acid oxygen not present (anaerobic respiration)

Electron Carriers (NADH & FADH2) + + + + NAD+ NAD 2 FAD 2 FAD + H H H (each hydrogen has an electron) H -e H -e -e H + NAD+ + NAD + 2 H -e H2 -e -e + FAD + 2 FAD

Electron Carriers (NADH & FADH2) Electron Transport Chain NADH is worth 3 ATP FADH2 is worth 2 ATP To extract ATP from NADH and FADH2, the electron carriers must first be transferred to the ETC

Glycolysis Occurs in cytosol Anaerobic (no oxygen required) Yields 2 ATP per glucose

Glycolysis 1. Phosphorylation 2. Cleavage 3. Oxidation (next slide) ATP Glucose (C6H12O6) ATP 1. Phosphorylation ADP ADP C P 2. Cleavage C P C P 2ADP 2ADP 2 ATP 2ATP NAD+ NAD+ NADH NADH 3. Oxidation (next slide) C C pyruvate pyruvate

Glycolysis 1. Phosphorylation 2. Cleavage 3. Oxidation No Oxygen ATP ATP 1. Phosphorylation ADP ADP C P 2. Cleavage C P C P 2ADP 2ADP 2 ATP 2ATP NAD+ NAD+ NADH NADH 3. Oxidation C C pyruvate pyruvate No Oxygen Oxygen Available Lactic Acid anaerobic respiration aerobic respiration 2. CAC 3. ETC

Anaerobic Respiration H -e -e H -e -e C NAD+ + C NAD Pyruvate Lactic Acid

Anaerobic Respiration Oxygen debt is the amount of O2 required to convert the lactic acid back to glucose after exercise. O oxygen H -e -e C C Lactic Acid Glucose (C6H12O6)

Electron Transport Chain Citric Acid Cycle & Electron Transport Chain

Glycolysis 1. Phosphorylation 2. Cleavage 3. Oxidation pyruvate ATP Glucose (C6H12O6) ATP 1. Phosphorylation ADP ADP C P 2. Cleavage C P C P 2ADP 2ADP 2 ATP 2ATP NAD+ NAD+ NADH NADH 3. Oxidation C C pyruvate pyruvate

Glycolysis 1. Phosphorylation 2. Cleavage 3. Oxidation No Oxygen ATP ATP 1. Phosphorylation ADP ADP C P 2. Cleavage C P C P 2ADP 2ADP 2 ATP 2ATP NAD+ NAD+ NADH NADH 3. Oxidation C C pyruvate pyruvate No Oxygen Oxygen Available Lactic Acid anaerobic respiration aerobic respiration 2. CAC 3. ETC

mitochondria Mitochondria are the powerhouse of cell. Most ATP are synthesized within mitochondria

Priming Pyruvic Acid for the Citric Acid Cycle Before pyruvic acid can enter the CAC it must first be converted into acetyl CoA C pyruvate 1 molecule of CO2 is released NAD+ NADH For each pyruvic acid, this reaction produces 1 CO2 molecule 1 NADH molecule 1 Acetyl CoA C acetic acid Coenzyme A Acetyl CoA is the substrate for the citric acid cycle. C acetyl CoA

Citric Acid Cycle The citric acid cycle occurs in the matrix of the mitochondrion.

+ Citric Acid Cycle acetyl CoA Co-Enzyme A is released oxaloacetic acid C C C citric acid 3 NAD+ Citric Acid Cycle 3 NADH C C FADH2 2CO2 FAD ATP ADP + P

Products of the citric acid cycle: 1 ATP 3 NADH 1 FADH2 2 CO2

Each Glucose = 2 turns of the CAC pyruvate pyruvate C C acetyl CoA acetyl CoA CAC CAC

electron transport chain (ETC) The ETC is located on the inner membrane of mitochondria An enzyme called ATP synthase forms ATP by attaching a phosphate to ADP ATP synthase is powered by the transfer of e- along a chain protein complexes that form the ETC. ETC

electron transport chain (ETC) The ETC produces 32-34 ATP per glucose Oxygen removes electrons from the final complex protein, so it is the final e- acceptor

Carbohydrate Metabolism Carbohydrate molecules from foods can: Enter catabolic pathways for energy production Enter anabolic pathways for energy storage React to form some of the amino acids Excess glucose can be converted into and stored as: Glycogen: Most cells, but liver and muscle cells store the most Fat to store in adipose tissue

catabolism of proteins, fats, & carbohydrates Carbohydrates, Lipids & Proteins can be broken down and used for ATP synthesis Most organic molecules enter the citric acid cycle as acetyl coA

DNA Replication & Protein Synthesis Chapter 4.6 DNA Replication & Protein Synthesis

Definitions Gene: portion of DNA that encodes one protein Genome: complete set of genetic instructions for an organism Human genome = 20,000 genes on 23 pairs of chromosomes Genetic (triplet) code: 3 letter DNA sequence that encodes for 1 amino acid

Genetic codes (triplets)

Properties of DNA DNA is a double-stranded helix Chromatin is located within the nucleus

DNA is wrapped around histone proteins Properties of DNA DNA is wrapped around histone proteins

Deoxyribonucleic Acid (DNA) Properties of DNA Hydrogen bonds Deoxyribonucleic Acid (DNA) Anti-parallel configuration The sugar in DNA is deoxyribose Sugar-phosphate backbone 4 Nitrogenous Bases

Properties of DNA DNA contains 4 nitrogenous bases Adenine (A) Thymine (T) Guanine (G) Cytosine (C) Adenine & Guanine are Purines: 2 rings Thymine & Cytosine are Pyrimidines: 1 ring

Complimentary Base Pairs A purine pairs with a pyrimidine 2 hydrogen bonds 3 hydrogen bonds

Complimentary strand: Example of complimentary base pairs. Original DNA strand: C A C C T G G G T G G A C C Complimentary strand:

DNA Replication S Phase The Cell Replicates its DNA

DNA Replication DNA replication is catalyzed by the enzyme DNA Polymerase

DNA Replication

Replication Fork

Replication Fork

DNA Replication new strand (green) DNA replication is Semi-Conservative – One strand of the replicated DNA is new, the other is the original molecule. original strand (teal)

DNA Replication The two DNA molecules separate during mitosis

Transcription & Translation Chapter 4.7 Transcription & Translation

RNA synthesis from DNA template Transcription RNA synthesis from DNA template

Properties of RNA single-stranded nucleic acid sugar = ribose Uracil (U) replaces Thymine (T) complimentary base pairs A – U G – C

RNA vs. DNA

There are several kinds of RNA Messenger RNA (mRNA): Conveys genetic information from DNA to the ribosomes Transfer RNA (tRNA): Transfers amino acids to the ribosomes during translation. Ribosomal RNA (rRNA): Provides structure and enzyme activity for ribosomes

Transcription Synthesis of a mRNA transcript from DNA template Transcription is catalyzed by RNA Polymerase Only 1 of the DNA strands is transcribed mRNA undergoes further processing & leaves the nucleus

Properties of mRNA Codon: 3 letter mRNA sequence that encodes for 1 amino acid. start codon: Initiates protein synthesis (AUG = start codon) stop codon: terminates translation (doesn’t code for an amino acid)

Properties of mRNA

Translation tRNA Amino acid 1 transfer RNA (tRNA) transports amino acid to mRNA anticodon on tRNA aligns with codon on mRNA

Translation Ribosomes Translation occurs on Ribosomes in cytoplasm 1 Amino acid Ribosomes Translation occurs on Ribosomes in cytoplasm anticodon codon codon mRNA

Translation

U A C 1 tRNA 3 2 A P A U G mRNA

3 2 U A C 1 A P A U G mRNA

3 3 peptide bond 1 2 A P U A C A U G mRNA

5 4 peptide bond 1 2 U A C 3 A P A U G mRNA

5 4 peptide bond 1 2 3 A P A U G mRNA

5 peptide bond 1 2 3 4 A P A U G mRNA

7 6 peptide bond 1 2 3 4 5 A P A U G mRNA

7 8 peptide bond 1 2 3 4 5 6 A P A U G mRNA

8 Polypeptide chain STOP CODON U G A A P mRNA

Once translation is complete chaperone proteins fold the protein into its configuration post-translational modification enzymes may further modify proteins after translation phosphorylation – adding a phosphate to the protein glycosylation – adding a sugar to the protein End of Chapter 4

Attribution Protein By Emw (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/1/10/Protein_NP_PDB_1m73.png Triglyceride By Wolfgang Schaefer (author) [Public domain], via Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/b/be/Fat_triglyceride_shorthand_formula.PNG "Amylose 3Dprojection.corrected" by glycoform - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Amylose_3Dprojection.corrected.png#/media/File:Amylose_3Dprojection.corrected.png "Beta-D-Glucose" by Yikrazuul - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Beta-D-Glucose.svg#/media/File:Beta-D-Glucose.svg "Isomers of oleic acid" by Edgar181 - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Isomers_of_oleic_acid.png#/media/File:Isomers_of_oleic_acid.png By Fir0002 [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/3/36/Large_bonfire.jpg "Molecular-collisions" by Sadi_Carnot - http://en.wikipedia.org/wiki/Image:Molecular-collisions.jpg. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Molecular-collisions.jpg#/media/File:Molecular-collisions.jpg Metabolic Pathways https://upload.wikimedia.org/wikipedia/commons/thumb/5/5d/Metabolism_pathways_(partly_labeled).svg/2000px-Metabolism_pathways_(partly_labeled).svg.png Genetic Code By Madprime (Own work) [CC0, GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/3/37/Genetic_code.svg G-C Base Paring By Jypx3 (Own work) [Public domain], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/2/21/GC_base_pair_jypx3.png A-T Base Paring By Jypx3 (Own work) [Public domain], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/6/67/AT_base_pair_jypx3.png Citation: Sha, K. and Boyer, L. A. The chromatin signature of pluripotent cells (May 31, 2009), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.45.1. http://www.stembook.org/node/585 https://upload.wikimedia.org/wikipedia/en/8/80/Sha-Boyer-Fig1-CCBy3.0.jpg By No machine readable author provided. Masur assumed (based on copyright claims). [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC BY 2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/0/0a/Replication_fork.svg DNA Replication Split Horizontal I, Madprime [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/3/33/DNA_replication_split_horizontal.svg By OpenStax College [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/1/11/0328_Transcription-translation_Summary.jpg By OpenStax College [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/f/f2/0324_DNA_Translation_and_Codons.jpg By Yikrazuul (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/a/ae/The_tRNA_cloverleaf_general.svg