Appendix for Science

Appendix A: Organic Chemistry Common Name Organic Chemistry Common Names Formyl Group Formaldehyde Formic Acid Acetyl Group Acetaldehyde Acetic Acid Acetone Acetylacetone Benzyl Group Benzaldehyde Benzoic Acid Benzoin Styrene Acryl Group Acrolein Acrylic Acid Carboxyl Group Carboxylate Ion Carbonate Ion Carbonic Acid Acetophenone Appendix B: The Heart Oxygen Transpor The Heart and Oxygen Transport Anatomy of the Heart Blood Flow Through the Heart Electrical Conduction Through the Heart Hemoglobin Found in blood . It has four polypeptide chains (tetramer), each combined with an iron-containing heme group. Most oxygen transport takes place through the use of hemoglobin. A small amount of oxygen will still dissolve in the plasma and be transported on its own. Each RBC contains !"#$ % $ &'( hemoglobin molecules. Cooperative When an O2 binds to one of the four binding sites, it becomes more Binding: likely that the remaining sites will bind to O2. CO2 and H + Allosterically inhibits Hemoglobin. That means CO2 and H+ will Inhibition: trigger the heme group to release its O2. Binding of Oxygen to a Heme Prosthetic Group Without O2, the Fe atom sits below the plane. When O2 binds, the electrons in the Fe atom rearrange so it fits in the hole and becomes level with the plane; also pulls His up towards the plane. The process starts when CO2 enters the RBC where carbonic anhydrase resides (the enzyme for the bicarbonate buffer). The CO2 combines with H2O to make H2CO3 which dissociates into H + and HCO3-. The H+ allosterically inhibits hemoglobin, e.g. changes the shape of hemoglobin, so it can’t hold onto the O2. Since CO2 initiates this process, the result is O2 is released near lots of CO2, which is Found in muscle tissue , it stores and releases oxygen. It is a monomer and contains where respiration is happening and O2 is needed. only 1 heme group. Myoglobin is NOT pH sensitive. Myoglobin ¯pH Þ ¯heme affinity for O2, curve shifts RIGHT (Bohr shift). O2 Affinity: Myoglobin has a much HIGHER oxygen affinity than hemoglobin. This means it can bind more securely to the oxygen. 2,3-BPG Another allosteric regulator. It places itself in the center of the Inhibition: tetramer and causes a and b subunits to release their O2. Note, fetal Heme Group: Myoglobin has only 1 heme group. This is why it cannot exhibit cooperative binding and it has a hyperbolic curve. hemoglobin has a and g (gamma) subunits. g subunits do not respond to 2,3-BPG, so HbF ends up with more O2 than HbA. 2,32,3-BPG: 2,3-BPG has NO AFFECT on myoglobin. BPG causes a RIGHT shift on the dissociation curve, like CO2 and H+. &2,3-BPG means your body needs more oxygen. Hemoglobin and Myoglobin Dissociation Curves CO2 Transport: After delivering O2 to a muscle, the CO2 that triggered the release of O2 will remain in the hemoglobin. The RBC then travels back to the lung, bringing the CO2 with it. p50: Oxygen pressure when 50% of hemoglobin has an O2 bound. P50 is LOWER for HbF due to the high affinity HbF has for oxygen. Myoglobin, hyperbolic, NOT cooperative % O2 Saturation Fetal HbF has a higher affinity for O2 compared to adult hemoglobin (HbA). Hemoglobin: This is because its tetramer contains g subunits, which don’t respond to 2,3-BPG. HbF dissociation curve has a LEFT shift, as if 2,3-BPG levels are low. Hemoglobin, sigmoidal, cooperative Sickle Cell A disease that affects hemoglobin. Caused when Val replaces Glu. Anemia: Hemoglobin aggregates into insoluble fibers. Glu Þ Val Hypoxia: Oxygen deprivation. )*+ (torr) Appendix C: Brai The Brain Anterior Cingulate motivation Motor Sensory FRONTAL LOBE planning PARIETAL LOBE touch & movement FRONT BACK OCCIPITAL LOBE vision Dorsolateral Prefrontal Cortex executive & logic TEMPORAL LOBE language Olfactory Bulb smell Lateral Orbitofrontal appropriate social / emotional response Hypothalamus the four F’s a basic emotions CEREBELLUM coordinate movement Entorhinal Complex memory Hippocampus memory BRAIN STEM body basics LIMBIC SYSTEM instincts & mood Cerebrum Cerebellum Higher brain function such as though and action. Cerebral Cortex: Layer of grey matter on the outside of the Cerebrum. Primary Cortex: Basic motor and sensory functions. Associative Cortex: Associates different types of information to do more complex processing and functions. Prefrontal Cortex: Located at the front of the brain, behind the forehead. It is part of the Cerebral Cortex. Associated with “cerebral” activities. Ex: If your instinct is to attack someone, your prefrontal cortex will think about it and tell you to walk away. Frontal Lobe: Reasoning, planning, speech production (Broca’s Area), movement, emotions, and problem solving. Temporal Lobe: Perception of auditory stimuli, memory, and language comprehension (Wernicke’s Area). Parietal Lobe: Movement, orientation, proprioception, recognition and perception of stimuli. Occipital Lobe: Visual processing. Hemispheres and Functions: Left: Language, logic, math and science, analytic thought, written, right-hand control. Right: Creativity, 3-D forms, imagination, intuition, art & music, left-hand control. Motor control. Regulation and coordination of movement, posture, and balance. The cerebellum does not initiate mvmt, it helps control and smooth out the mvmt. Movement The cerebellum receives a motor plan from the Cerebrum and Control: compares it to position sense information from Somatosensory Neurons. It then determines if corrections are necessary. If needed, the cerebellum will tell the cerebrum to adjust the mvmt. Speech Control: Cerebellum coordinates the mouth muscles that produce speech. Damage: Damage to the cerebellum produces disorders in fine movement, equilibrium, posture, and motor learning. The damage could also impair speech enunciation or eye movement. Limbic System Sits on top of the brain stem. Hypothalamus: “Below the thalamus”. Regulates the autonomic nervous system via the endocrine system. The four Fs. Amygdala: Aggression center. Fear and anxiety. Stimulation causes more fear & anxiety. Damage causes mellow mood, and less fear; hypersexualtiy, disinhibition. Kluver-Busy Syndrome is the destruction of the amygdala. Thalamus: Sensory relay station. Hemispheres and Emotion: Left: Positive emotions, more sociable, joyful, enthusiastic. Right: Negative emotions, socially isolated, fearful, avoidant, depressed. Hippocampus: Converts STM ® LTM. If damaged, new memories fail to form. Brain Stem Connects all parts of the nervous system together, including cranial nerves. Pons: Regulates waking and relaxing. Reticular Alertness and motivation. Controls autonomic functions such as Formation: circulation, respiration and digestion. Also plays a role in higher cognition functions. Medulla: Regulates the autonomic activity of the heart and lungs. Long Tracts: Collections of axons connecting the cerebrum to the spinal cord, passing through the brainstem. Upper motor neurons signaling down and somatosensory long tracts signaling up. Appendix D: Endocrine Organs and Hormone Endocrine Organs and Hormones Hypothalamus “Below the thalamus”. Regulates the autonomic nervous system via the endocrine system. The four F’s. GnRH: Gonadotropin-Releasing Hormone. Stimulates the release of FSH and LH. GHRH: Growth Hormone-Releasing Hormone. Stimulates the release of GH. TRH: Thyrotropin-Releasing Hormone. Stimulates the release of TSH . CRH: Corticotropin-Releasing Hormone. Stimulates pituitary synthesis of ACTH. PIF or A catecholamine. As a neurotransmitter, most rewards will increase Dopamine: the level of dopamine. ADH and Produced in the hypothalamus; released from the posterior pituitary. Oxytocin: Pancreas A large gland behind the stomach. It secretes digestive enzymes into the duodenum. Embedded in the pancreas are the islets of Langerhans which secrete insulin and glucagon into the blood. Insulin: Peptide hormone secreted by b-islet cells. Its function is to help glucose enter the cells. "Glucose triggers insulin secretion. Inhibited by norepinephrine. Glucagon: Peptide hormone secreted by a-islet cells. Its function is to help glucose enter the blood stream. ¯Glucose triggers glucagon secretion. Somatostatin: Growth Hormone-Inhibiting Hormone. A peptide hormone (GHIH) secreted by d-islet (delta) cells. Inhibits GH and also leads to ¯insulin and ¯glucagon. Gonads A gland that produces gametes (sex cells) and sex hormones. In males, the gonads are testicles, in females they are ovaries. Testosterone: Produced by the testes in men and ovaries in women with a small amount produced by the Adrenal Cortex. In males, it is the primary sex hormone and an anabolic steroid. Estrogen: Produced by the ovaries. It is the primary female sex hormone and leads to the development of secondary sexual characteristics. Estrogen also regulates the menstrual cycle. ¯milk production. Anterior Pituitary Anterior lobe of the pituitary gland. It regulates several physiological processes including stress, growth, reproduction, and lactation. FSH: Follicle-Stimulating Hormone. A gonadotropin. In males it promotes spermatogenesis. In females it stimulates growth of ovarian follicles. LH: Luteinizing Hormone. A gonadotropin that induces ovulation. ACTH: Adrenocorticotropic Hormone. Stimulates the production and release of cortisol. TSH: Thyroid-Stimulating Hormone. Stimulates the Thyroid to produce Thyroxine (T4) and Triiodothyronine (T3), which stimulates metabolism. Prolactin: Stimulates milk production. Endorphins: ¯Pain Growth Also known as somatotropin. Stimulates growth and cell Hormone: reproduction. Posterior Pituitary Posterior lobe of the pituitary gland. ADH: Antidiuretic Hormone. A peptide hormone synthesized in the (Vasopressin) hypothalamus and released by the posterior pituitary. It regulates the tonicity of body fluids. ADH is released in response to hypertonicity and causes the kidneys to reabsorb H2O. Results in concentrated urine and reduced urine volume. Can also "BP. Oxytocin: A peptide hormone synthesized in the hypothalamus and released by the posterior pituitary. During childbirth, it increases uterine contractions and is released in response to cervix stretching. Also increases milk production and certain bonding behaviors. Thyroid Gland In the neck and below the Adam’s Apple. Secretes thyroid hormones that regulate metabolism. Also helps regulate calcium homeostasis. T4 & T3: Thyroxine (T4) and Triiodothyronine (T3). T4 is a precursor to T3. Regulates metabolism. Created from Iodine and Tyrosine. Calcitonin: Builds bone "Ca2+ in bone "Ca2+ excretion from kidneys ¯Ca2+ in blood ¯Ca2+ absorption in gut Progesterone: Produced by the ovaries. Prepares the endometrium for potential pregnancy following ovulation. ¯milk production Parathyroid Glands Pineal Gland A collection of 4 parathyroid glands located on the back of the thyroid. Primary function is to maintain the body’s Ca2+ and K+ levels so that the nervous and muscular systems can function properly. Located in the epithalamus, tucked into a groove between the two thalamus halves. Melatonin: Regulates sleep / wakefulness and controls the circadian rhythm. Adrenal Cortex Sits along the perimeter of the adrenal gland (top of kidney). Mediates stress response. Glucocorticoids: Cortisol is released during stress. "Glucose in blood through gluconeogenesis ¯Immune system ¯Protein synthesis Cortisone is similar to Cortisol. ¯Immune response so ¯inflammation and ¯allergic response Mineralcorticoids: Aldosterone causes "Na+ in blood which "BP. It is regulated by K+ and angiotensin II which is derived from angiotensin I. Androgens: Converted to Testosterone and Estrogen in the gonads. PTH: Parathyroid Hormone. Bone breakdown . ¯Ca2+ in bone ¯Ca2+ excretion from kidneys "Ca2+ in blood "Ca2+ absorption in gut Activates Vitamin D (Calcitriol) Adrenal Medulla Sits on top of the kidney. Adrenal Medulla is located at the center of the adrenal gland, surrounded by the adrenal cortex. It converts tyrosine into catecholamines. Epinephrine: "HR and "BP. Primarily a hormone. Also an anti-histamine. Norepinephrine: "HR and "BP. A hormone and a neurotransmitter; inhibits insulin. Dopamine: The adrenal medulla secretes a small amount of dopamine. Appendix E: Lab Technique Lab Techniques Gel Electrophoresis Gel electrophoresis Separates macromolecules (proteins, DNA, or RNA). For proteins and small molecules the gel is polyacrylamide. For larger molecules (>500 bp), the gel is agarose. Negatively charged molecules travel toward the anode at the bottom. Large molecules will move SLOWER. Coomassie Blue stain can be used for visualization. ! NEGATIVE cathode Native-PAGE: A polyacrylamide gel electrophoresis method for proteins using NON-DENATURING conditions. Proteins keep their native charge and structure so they are separated based on charge and size. SDS-PAGE: A polyacrylamide gel electrophoresis method for proteins using DENATURING conditions. Sodium Dodecyl Sulfate denatures the proteins and gives the proteins a uniform charge. This allows them to be separated solely on mass, thus, you can estimate the protein’s molecular mass. Reducing SDS- Exactly the same as SDS-PAGE, but with the addition of a PAGE: reducing agent, b-mercaptoethanol, which will reduce the disulfide bridges and result in a completely denatured protein. Isoelectric A gel electrophoresis method that separates proteins on the Focusing: basis of their relative contents of acidic and basic residues. The gel has a pH gradient and the proteins will migrate through the gel until they reach the pH that matches their isoelectric point. At the pI, the protein has a neutral charge, so it will no longer be attracted to the anode and it will stop migrating. Southern Blotting: Detection of a specific DNA sequence in a sample. S D Northern Blotting: Detection of a specific RNA sequence in a sample. N R Western Blotting: Detection of a specific PROTEIN in a sample. W P Chromatography # POSITIVE anode Sanger DNA Sequencing Chain termination method. Uses dideoxy nucleotides. The ddNTP lacks a hydroxyl group on the 3’ carbon of the sugar ring. With the 3’ hydroxyl group missing, no more nucleotides can be added to the chain. The chain ends with the ddNTP, which is marked with a particular color of dye depending on the base that it carries. After mixing all components, it is virtually guaranteed that a ddNTP has incorporated at every single position of the target DNA strand. The strands are run through gel electrophoresis to separate them based on length. The colored dye is read and is used to establish the DNA sequence. Polymerase Chain Reaction Used to make many copies of a specific DNA region in vitro. The key ingredients of PCR are Taq polymerase , primers, template DNA, and nucleotides (DNA building blocks). The ingredients are assembled in a tube, along with cofactors needed by the enzyme, and are put through repeated cycles of heating and cooling that allow DNA to be synthesized. Separates two or more molecules from a mixture. Primer: Must have high GC content and either a G or C at each end. Example: 5’-GCATAGAAGCATTCCGC-3’ Stationary Phase: Typically polar. Polar molecules elute slower. Mobile Phase: Typically nonpolar. Nonpolar molecules elute faster. Liquid Chromatography: Silica is used as the stationary phase while toluene or another nonpolar liquid is used as the mobile phase. Taq Polymerase: The DNA polymerase typically used in PCR. Named after the heat-tolerant bacterium from which it is isolated (Thermos aquaticus). Very heat-stable and most active around 70¡C. Steps: 1. 2. 3. High-Performance Liquid HPLC is a type of liquid chromatography that uses high Chromatography: pressure to pass the solvent phase through a more finelyground stationary phase which increases the interactions between the moelcuels and the stationary phase. This gives HPLC higher resolving power. Denaturation (96¡C) Annealing (55 - 65¡C) Extension (72¡C) Cycle is repeated until you have enough DNA Gas Chromatography: Vaporizes the liquid before separation. Molecules are separated based on polarity and boiling point. The stationary phase is a thin layer of material applied to the inside of the column. Typically the polarity of the stationary phase matches that of the solute. The mobile phase is an inert gas. Gel-Filtration Separates molecules by size rather than polarity. Smaller Chromatography: molecules enter the porous gel beads allowing them to (Size-exclusion) elute later. Larger molecules will elute faster because they do not fit in the pores and will not be slowed down. Ion Exchange Separates proteins by their net charge. The column is Chromatography: filled with charged beads, either POS or NEG. Cation Exchange: NEG beads used, NEG proteins elute 1st. Anion Exchange: POS beads used, POS proteins elute 1st. Affinity Chromatography: Separates proteins based on their affinity for a specific ligand. Beads are bound to a specific ligand and proteins with a high affinity for that ligand will bind to the beads. Proteins with a low affinity for the ligand will elute first. Thin-Layer Sheet coated in polar silica gel. Molecules are spotted on Chromatography: the bottom of the sheet. Sheet is placed in a nonpolar liquid. Mobile phase travels up the plate using capillary action. Nonpolar molecules have the highest Rf value. Thin-Layer Chromatography Solvent front Nonpolar Polar '()*+,-.")/0*"102.' Retention $ & " % '()*+,-.")032.,*"%40,*"102.' Factor: Appendix F: DNA and RN DNA and RNA DNA Structure DNA A polymer made up of monomers called nucleotides. Long strands Structure: form a double helix which runs antiparallel. Charge: DNA is negatively charged due to its phosphate backbone. Nucleotides: Each nucleotide has three parts: ¥ 5-carbon sugar, (DNA uses deoxyribose) ¥ Nitrogen-rich base ¥ Phosphate Group ¥ Note: A nucleoside lacks the phosphate group Example of a Nucleotide: Guanosine diphosphate (GDP) Nucleotide Pairs: ¥ Adenine – Thymine 2 H-bonds ¥ Guanine – Cytosine 3 H-bonds, stronger ¥ Note: RNA has U instead of T Structural DNA backbone is held together via phosphodiester bonds that Bonds: form between the sugar and the phosphate groups. Hydrogen bonds hold the nucleotide bases together inside the double helix. Pyrimidines 1 ring: A pyrimidine ring Purines 2 rings: A pyrimidine ring fused to an imidazole ring Nitrogenous Bases Cytosine (DNA only) Pairing: Thymine Uracil Adenine Guanine (RNA only) purine + pyrimidine = uniform width purine + purine = too wide pyrimidine + pyrimidine = too narrow DNA Double DNA double helix has a diameter of 20 angstroms. Helix Width: RNA: Also a polymer of nucleotides, but differs from DNA in three major respects: 1. RNA is usually single stranded . 2. The sugar in RNA is ribose, which is more reactive than deoxyribose. 3. The nitrogenous base is Uracil (U), not thymine (T). mRNA: Messenger. Encodes AA sequence. tRNA: Transfer. Brings AA to ribosomes during translation. rRNA: Ribosomal. Form ribosomes. snRNA: Small nuclear. Form spliceosomes that remove introns. Levels of DNA Packaging ¥ ¥ ¥ ¥ Strands of DNA wrap around a histone protein forming nucleosomes Nucleosomes coil together forming chromatin Chromatin loops and coils together forming supercoils Supercoils bunch together forming chromosomes DNA vs. RNA Proofreading: DNA replication has proofreading while RNA transcription does not. This makes DNA replication more accurate than RNA transcription. Stability: RNA is less stable than DNA because it contains the sugar ribose compared to DNA’s deoxyribose. As a result, mRNA degrades rapidly in the cytoplasm. DNA Double Helix Histones at the core of Nucleosomes Chromatin Supercoiled DNA Chromosome Appendix G: DNA Replicatio DNA Replication DNA-Polymerase (Pola) DNA-Ligase RNA Primase RNA Primer Lagging Strand Okazaki Fragment Leading Strand Topoisomerase DNA-Polymerase (Pold) Helicase Single Strand Binding Proteins Topoisomerase: Unwinds the DNA double helix. Helicase: Breaks the hydrogen bonds between the nitrogenous bases in order to separate the DNA strands. Single Strand (SSB). Binds to ssDNA and prevents annealing of ssDNA into Binding Protein: double-stranded DNA. DNA Primase: Catalyzes the synthesis of the RNA primer. RNA Primers: Short RNA nucleotide sequences that are complementary to the ssDNA. They allow DNA replication to start. DNA Polymerase: Adds nucleotides to the growing strand. It reads the template 3’ ® 5’ and synthesize the new strand 5’ ® 3’. DNA Polymerase also removes the RNA primer at the end of the strand. There are many varieties of DNA polymerase. Eukaryotes use Pol a, b, d, e etc. Prokaryotes use Pol I, II, III, IV, V. Okazaki Short, newly synthesized DNA fragments that are formed on Fragment: the lagging template strand during DNA replication. DNA Ligase: Joins DNA strands together by catalyzing the formation of phosphodiester bonds. Appendix H: The Central Dogm The Central Dogma DNA RNA Transcription Protein Translation 1. RNA is transcribed from a DNA template. 2. In eukaryotes, the RNA transcript (pre- mRNA) is spliced and modified to produce mRNA, which moves from the nucleus to the cytoplasm. 4. Each amino acid attaches to its proper tRNA with the help of a specific enzyme and ATP. 3. The mRNA leaves the nucleus and attaches to a ribosome. 5. A succession of tRNAs add their amino acids to the polypeptide chain as the mRNA is moved through the ribosome one codon at a time. When completed, the polypeptide is released from the ribosome. DNA 5’ ATGGGGCTCAGCGAC 3’ Sense strand 3’ TACCCCGAGTCGCTG 5’ Antisense strand Transcription mRNA 5’ AUGGGGCUCAGCGAC 3’ mRNA with codons UACCCCGAGUCGCUG tRNA with anti-codons Met Gly Leu Ser Asp Peptide Translation Protein Appendix I: Amino Acid Amino Acids Hydrophobic Polar Neutral Glycine, Gly, G Serine, Ser, S Lysine, Lys, K Aspartic Acid, Asp, D Alanine, Ala, A Threonine, Thr, T Arginine, Arg, R Glutamic Acid, Glu, E Valine, Val, V Tyrosine, Tyr, Y Histidine, His, H Leucine, Leu, L Cysteine, Cys, C Isoleucine, Ile, I Asparagine, Asn, N Methionine, Met, M Glutamine, Gln, Q Basic, , Hydrophilic Acidic, Proline, Pro, P Phenylalanine, Phe, F Tryptophan, Trp, W Indole Group (Tryptophan) Imidazole Group (Histidine) Guanidinium Group (Arginine) Appendix J: Enzyme Inhibitio Enzyme Inhibition Vmax: The maximum rate of the reaction Km: The amount of substrate needed for the enzyme to work half as fast as it is capable of. !Km = ¯enzyme-substrate affinity ¯Km = ! enzyme-substrate affinity Competitive Inhibition Uncompetitive Inhibition Noncompetitive Inhibition Vmax no change !KM ¯Vmax ¯KM ¯Vmax KM no change An uncompetitive inhibitor binds only to the enzyme–substrate complex. A noncompetitive inhibitor binds at the allosteric site, away from the active site. It does NOT prevent the substrate from binding to the active site. A competitive inhibitor binds at the active site and thus prevents the substrate from binding. Lineweaver-Burk Plots Lineweaver-Burk Plots ¥ A double-reciprocal plot of ! " vs. ! [$] -. slope = , " ./0 ¥ Left side of the graph is theoretical because you can’t have negative substrate or velocity higher than Vmax ¥ Vmax and Km can be more precisly calculated using Lineweaver-Burk because you are extrapolating out theoretical values. ¥ Michaelis-Menton curves show observed values only, not theoretical values. This makes calculations using Michaelis-Menton less accurate than Lineweaver-Burk. ¥ Lineweaver-Burk allows the different types of inhibition to be visualized more clearly. Michaelis-Menten Curves Vmax, Vmax V = reaction rate Competitive Inhibitor: Vmax no change, !KM ! 1 Uncompetitive Inhibitor: ¯Vmax, ¯KM Vmax Vmax 1 max Vmax ! 1 ! 1 Vmax Noncompetitive Inhibitor: ¯Vmax, KM no change Vmax Km Km Km Km [S] = substrate concentration Appendix K: Metabolism Overview Metabolism Overview Proteins amino acids Carbohydrates glucose, fructose, galactose Fats and Lipids fatty acid, glycerol Glycogenesis Nitrogen Pool Glycogen Glucose 6-Phosphate b-oxidation Glycogenolysis Glycolysis Gluconeogenesis Tissue Protein Fatty Acid Synthesis Lactic Acid Pyruvate PDC Acetyl-CoA NH3 CO2 Oxaloacetate O2 ADP Urea Cycle ADP ADP 2H + Citric Acid Cycle Electron Transport Chain 2eATP Fumarate Urea CO2 ATP ATP H 2O Appendix L: Glycolysi Glucose has 6 carbons Glycolysis Occurs in cytoplasm STEPS Pyruvate has 3 carbons. Glycolysis produces two Pyruvates Glucose Hexokinase ATP Induced fit Regulated by G 6-P feedback ADP 1 Glucose 6-phosphate 2 Phosphoglucose isomerase Fructose 6-phosphate Phosphofructokinase (PFK) ATP Committed step Regulated by ATP/AMP ratio and Citrate 3 ADP Fructose 1,6-bisphosphate Aldolase Dihydroxyacetone phosphate Triose phosphate isomerase 5 4 Glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate dehydrogenase Pi, NAD+ NADH 6 1,3-Bisphosphoglycerate Phosphoglycerate kinase ADP ATP 7 3-Phosphoglycerate 8 Phosphoglycerate mutase 2-Phosphoglycerate Note: PEP is high energy because the phosphoryl group traps PEP in its enol form. When the phosphoryl group is donated to ADP, making ATP, the enol converts to a more stable ketone (pyruvate), which releases a lot of energy. H2O Phosphoenolpyruvate (PEP) Pyruvate Kinase Reactants 1 Glucose 2 ATP 4 ADP 2 NAD+ 2 Pi Products 2 Pyruvate 2 ADP 4 ATP (2 net gain) 2 NADH 2 H+ 2 H 2O 9 Enolase ADP Regulated by covalent modification. Phosphorylated = inactive !Alanine = inactive ATP 10 The Fate of Pyruvate Pyruvate Cori Cycle Citric Acid Cycle Appendix M: Gluconeogenesi Gluconeogenesis Takes place mainly in the liver and, to a lesser extent, in the kidneys Glucose Pi Glucose 6-phosphatase Found only in liver. H 2O Glucose 6-phosphate Phosphoglucose isomerase Fructose 6-phosphate Pi Fructose 1,6-bisphosphatase H 2O Control point of gluconeogenesis Activated by ATP, inhibited by AMP and fructose 2,6-bisphosphate. Fructose 1,6-bisphosphate Aldolase Dihydroxyacetone phosphate Triose phosphate isomerase Glyceraldehyde 3-phosphate Pi, NAD+ Glyceraldehyde 3-phosphate NADH dehydrogenase 1,3-Bisphosphoglycerate ADP Phosphoglycerate kinase ATP 3-Phosphoglycerate Phosphoglycerate mutase 2-Phosphoglycerate Enolase H 2O GDP, CO 2 Phosphoenolpyruvate (PEP) GTP The combination of Pyruvate Carboxylase and PEPCK is used to circumvent the action of Pyruvate Kinase. Phosphoenolpyruvate Carboxykinase (PEPCK) Activated by glucagon and cortisol. Oxaloacetate Pyruvate ADP + Pi ATP, HCO3 Pyruvate Carboxylase Activated by Acetyl-CoA. Begins in mitochondria and uses malate as intermediate to exit the mitochondria. Appendix N: Citric Acid Cycl Citric Acid Cycle Eukaryotes: CAC occurs in mitochondrial matrix Pyruvate Dehydrogenase Complex Prokaryotes: CAC occurs in cytoplasm Step 1 Step 3 (Rate limiting step) Step 4 Reactants Products 1 Acetyl CoA 3 NAD+ 1 FAD 1 ADP 1 Pi 3 H 2O 2 CO2 3 NADH 1 FADH2 1 ATP 3 H+ Step Regulatory Enzyme 1 Citrate Synthase 3 Isocitrate dehydrogenase (Rate limiting enzyme) 4 a-Ketoglutarate dehydrogenase complex Inhibitors / Activators Inhibitors: ATP, NADH, Citrate, Succinyl-CoA Activator: ADP Inhibitors: ATP and NADH Activators: ADP and NAD+ Inhibitors: Succinyl-CoA, NADH, ATP Activator: ADP Appendix O: Oxidative Phosphorylatio Oxidative Phosphorylation (ETC and Chemiosmosis) Eukaryotes: ETC occurs in mitochondria Prokaryotes: ETC occurs in the cell membrane Total Energy Produced from One Glucose Glycolysis: Pyruvate Dehydrogenase Complex: Citric Acid Cycle: 2 NADH and 2 ATP 1 pyruvate makes 1 NADH. Glucose forms 2 pyruvates, so PDC generates a total of 2 NADH per molecule of glucose. One Acetyl-CoA leads to 3 NADH, 1 FADH2, and 1 GTP. Glycolysis forms two pyruvates, so two AcetylCoA molecules exit the PDH complex. A total of 6 NADH, 2 FADH2 , and 2 GTP per molecule of glucose. 2 NADH + 2 ATP = 7 ATP 2 NADH = 5 ATP 6 NADH + 2 FADH2 + 2 GTP = 20 ATP 1 Glucose = 32 ATP Each NADH Þ 2.5 ATP; 10 NADH form 25 ATP Each FADH2 Þ 1.5 ATP; 2 FADH2 form 3 ATP Appendix P: More Metabolic Pathway Fatty Acid Synthesis b -Oxidation Occurs in the cell’s cytoplasm Occurs in the mitochondrial matrix Fatty Acid Acyl-CoA FAD Reduce Oxidation FADH2 NADPH H 2O H 2O Dehydration Hydration NAD+ Reduce Oxidation NADH NADPH Initiation of Fatty Acid Synthesis 1. Fatty acid synthesis begins with the transfer of Acetyl-CoA from the mitochondria to the cytosol. 2. Activation of Acetyl-CoA through the synthesis of Malonyl-CoA. Enzyme is Acetyl-CoA Carboxylase (regulatory enzyme for fatty acid synthesis). 3. Malonyl-CoA elongation using ACR DR. CoA, CO2 CoA-SH Condense Acetyl-CoA attaches to Acyl Carrier Protein (ACP) Thiolysis Acetyl-CoA + (Acyl-CoA 2 carbons less) Attach b -Oxidation Energy Products Malonyl-CoA Example: C16 Fatty Acid (C2) Acetyl-CoA = 8 # Rounds of b -Oxidation = 7 NADH: 7 FADH2: 7 Urea Cycle Pentose Phosphate Pathway Occurs in the cytosol and mitochondrial matrix of liver. and its link to glycolysis. Occurs in cytosol. Fatty acid synthesis 2 NADP+ Citric Acid Cycle 2 NADPH Glutathione reduction Glucose H2O CO2 Fumarate Arginine Urea Ornithine Carbamoyl Phosphate + CO2 + NH4+ Argininosuccinate Citrulline Aspartate Other reactions, such as detoxification Glucose 6-phosphate Ribulose 5-phosphate Fructose 6-phosphate Xylulose 5-phosphate Glyceraldehyde 3-phosphate Ribose 5-phosphate Nucleotide biosynthesis Oxaloacetate Mitochondrial Matrix Citric Acid Cycle Pyruvate Glycolysis Pentose Phosphate Pathway Appendix Q: Essential Equation Kinematics Thermochemistry Waves Electricity & Magnetism AB $ AC D E'FG Fn $ r Z f A $ l'Ÿ R$ ABH $ ACH s D I'E'FJ n $ ' H 't'u'v K FJ $ AC 'FG D' H 'E'LFGMH v $' f $ Zh'FT Light r $ W'xy 6'OP RN $ ' Q FxQS: $ ' Fx|Q8; Z' FxQpXN\ AV $ TC 'U+('Lq M RBQ[N\[8: $ µ 'R:8Q6X] Gay-Lussac: R^ $ Charles: _'`a 'b P cP R^ $ W'd •a •P f $ 'R'g'0,U'L qM i j $' ‚ bP } ~ $m € h $' K K K ba Ë $' K Z €Pª«¬-® K ‡ˆ‰Š R $ Zm'J Œ $' K n $ H 'm'J H W$ n $ W'd'o 68] y P €«¬«¯«-® u $' M •• ƒ„ $ ' Z•–d'‡„” Š c ŒK 'TK $ ŒH 'TH Inclined Plane p' $ —'Œ'˜'v R[:N][:p $ W'd U+(Lq M FvB $ —'mB 'W Rq $ W'd 0,ULq M FvY $ —'mY 'W RBQ[N $ µ 'W'd 0,ULq M ™ˆ $ b•Žš 68]›œ›•ž eÊ ¼ ¨ l $' l $' H'´ € ¶'´ € $' F• ¨ K r '´ ¼ TQ67 $ ' ÇQ67 $ ' •Ì•Í ÎH ±Ì•Í ÎH ² ''Lt $ 4? I? µ M Resistors in Series u\8\ $ uK D uH D Ï '''Lt $ 4? 1? µ M ŸYpX\ $ 'ç“K Z ŸH ç b•Ž ‘ $ Œ' 3'L’',“'„” ) _'`a 'bP à eÊ ¼ g b' $ 4& -,† °± ³ ƒ„ $ ƒ…X D -,† ‡‹ˆŠ $ Â'T lNp]] $ lNX\£ Z lX: Sound Solutions K c n¡ÈÉ $ 'H 'Ë'FTH K $ ' D' ¨ ¨© œ o'Ÿ $ u'L $m ¿'Áa 'ÁP r $ Ë'FT K $m • l¡ÈÉ $ ¨ $ ' ¨© œ ± $ R'A'0,U'LqM kl $' H 'W'AH n$Z • ~ Avogadro: t $ e'R U+(LqM T $ Ç'u Ÿ $ ' 'e H Boyle: h'T $ m RX'8:'Y $ ZRY'8:'X h $' Œ h'T $ t'u'v R $ W'E l c R $ —'Æ'Å U+(LqM $ o'Ÿ ¤ 3 0 ¥ I2&' 3 4&2&II' 3 ' 4&Hs Gas Constant: ˜ $ Ñ214/' Ò ˜ $ &2&Ñ&I4' y'X\6 68]'Ó Planck’s Constant: ¤ $ >2>I>' 3 ' 4&?&&&'@ Newton: Õ $ ' ¿^'6 7P Joule: § $ ' ¿^'6P $ Õ') 7P Pascal: Ö¾ $ ' qP 6 Volt: Ohm: Ò × Ú ˆ Amp: Farad: × 7pN × Ú Watt:' Ò 7pN $ Ø'Ù