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Download Outline06 Metabolism - Napa Valley College
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Biology 219 – Human Physiology Clemens Cellular Metabolism - Part 1 Text: Ch 4 A. Cellular Respiration - metabolism of substrates to release energy to form ATP ATP Oxidation of glucose: glucose + 6 O2 → 6 CO2 + 6 H2O + energy heat 1. Glycolysis - partial breakdown of glucose to pyruvate: glucose → 2 pyruvate - occurs in the cytosol - multi-step pathway a. energy investment steps - add 2 high-energy phosphates from ATP b. cleavage step - splits 6C sugar into two 3C molecules c. energy capture steps - yield 2 NADH and 2 ATP Each NADH carries 2 high-energy electrons: NAD+ + 2 H → NADH + H+ oxidized reduced - pyruvate is the branch point between aerobic and anaerobic metabolism of glucose Aerobic metabolism - pyruvate goes to Transition Step and Citric Acid Cycle in the mitochondria - NADH donates electrons to the Electron Transport Chain yield: 2 ATP + 2 NADH per glucose product (intermediate): 2 pyruvate Anaerobic metabolism - pyruvate converted to lactate via the lactic acid pathway in the cytosol pyruvate + NADH → lactate + NAD+ - NADH is converted back to NAD+ needed to continue glycolysis yield: 2 ATP per glucose product: 2 lactate + 2 H+ 2a. Transition Step from Glycolysis to the Citric Acid Cycle: pyruvate (3C) + CoA + NAD+ → acetyl CoA (2C) + CO2 + NADH yield: 1 NADH (x 2) product: 1 CO2 (x 2) acetyl CoA is a key intermediate which transfers 2C units to the Citric Acid Cycle 2b. Citric Acid (Krebs) Cycle - complete oxidation of 2C units from acetyl CoA → 2 CO2 - occurs in the matrix of the mitochondria - multi-step sequence of redox reactions first step: acetyl CoA (2C) + oxaloacetate (4C) → citrate (6C) + CoA subsequent steps: citrate is converted back to oxaloacetate, - 2 C atoms are fully oxidized to form 2 CO2 molecules - high-energy electrons are transferred to NADH and FADH2 (reduced coenzymes) yield: 3 NADH + 1 FADH2 + 1 ATP (x 2) product: 2 CO2 (x 2) 3. Electron Transport Chain - electron carrier proteins are located in the inner membrane of the mitochondria 3 major protein complexes (I, III, IV) cytochromes - iron-containing proteins in the E.T.C. - NADH and FADH2 donate high-energy electrons to the E.T.C. - electrons move “downhill” through E.T.C., release energy for ATP production - oxygen (O2) is the final electron acceptor: ½ O2 + 2 e- + 2 H+ → H2O 4. ATP Synthesis Chemiosmotic Coupling mechanism: - E.T.C. complexes act as H+ pumps - H+ is pumped “uphill” from the matrix into the intermembrane space containing high [H+] - H+ moves back “downhill” through the ATP synthase in the inner membrane - ATP synthase phosphorylates ADP to ATP Complete oxidation of glucose: yield: ~ 30 ATP per glucose end products: 6 CO2 + 6 H2O Biology 219 – Human Physiology Cellular Metabolism - Part 2 Clemens Text: Ch. 4 and 22 B. Glycogen Metabolism 1. Glycogen synthesis (glycogenesis) glucose + ATP → glucose-6-P → glycogen - glycogen is stored mostly in liver and skeletal muscle cells - the hormone insulin stimulates glycogen synthesis when blood [glucose] is high 2. Glycogen breakdown (glycogenolysis) glycogen + Pi → glucose-6-P → glucose - in liver: glycogen → glucose → released into blood to maintain glucose homeostasis - the hormone glucagon stimulates glycogenolysis in liver when blood [glucose] is low - in skeletal muscle: glycogen → glucose-6-P → metabolized in active muscle cells C. Protein Metabolism 1. Proteolysis a. Protein catabolism - hydrolysis of polypeptides → amino acids b. Deamination - removal of the amino group amino acids → keto acids + NH3 (ammonia) keto acids enter the Citric Acid Cycle → CO2 + H2O + energy NH3 is converted to urea → excreted by the kidneys (transamination: -NH2 group is transferred to another amino acid) 2. Protein Synthesis (will cover later) 3. Tissue Utilization of Proteins - normal protein turnover in cells - protein metabolism increases during starvation, injury, heavy exercise, high-protein diet D. Fat Metabolism 1. Lipolysis - catabolism of fats and other lipids a. Hydrolysis of triglycerides triglyceride + H2O → fatty acids + glycerol b. Beta oxidation - stepwise oxidation of fatty acids - fatty acids are broken down into 2C units → acetyl CoA → Krebs Cycle → CO2 + H2O - high energy yield: >100 ATP per fatty acid > 2X more energy yield per gram than carbohydrates 2. Lipid Synthesis - fatty acids are synthesized from 2C units of acetyl CoA - fatty acids are combined with glycerol to form triglycerides and phospholipids 3. Tissue Utilization of Fatty Acids - triglycerides are stored mostly in adipose tissue - lipids are transported in the blood by lipoproteins: HDL, LDL - liver, heart, and resting skeletal muscle use mostly fatty acids for energy - fatty acids are broken down only by aerobic metabolism - excessive fat catabolism → formation of ketone bodies (→ metabolic acidosis) E. Gluconeogenesis = formation of glucose from non-carbohydrate sources: amino acids, glycerol, lactate - occurs mostly in the liver - important during fasting or glucose depletion (e.g., exercise, stress, low carbo diet) - stimulated by hormones cortisol and glucagon F. Interconversion of Substrates glucose → acetyl CoA → fatty acids (lipid synthesis) amino acids → keto acids → glucose (gluconeogenesis) glucose → keto acids → amino acids (transamination) (Note: fatty acids can not be converted into glucose or amino acids)