Human Anatomy & Physiology II Metabolism PDF

Human Anatomy & Physiology II (PSIO202) Metabolism  Objectives 1. Understand what metabolism is, and how to measure it. 2. Understand the role of ATP in energy storage within cells. 3. Describe the major steps and organs involved in carbohydrate, lipid and pr...

Human Anatomy & Physiology II (PSIO202) Metabolism  Objectives 1. Understand what metabolism is, and how to measure it. 2. Understand the role of ATP in energy storage within cells. 3. Describe the major steps and organs involved in carbohydrate, lipid and protein metabolism. *For carbohydrates, note which steps require oxygen. *Understand the role of the liver in storage and metabolism of nutrients. 4. Compare the absorptive and post‐absorptive states in terms of nutrient use and transport. 5. Describe the role of the endocrine system in nutrient metabolism. (e.g. effects of insulin, glucagon, epinephrine, cortisol, hGH).  Metabolism = “the chemical processes that occur within an organism to maintain life” “converting food into energy” “the life-sustaining chemical reactions in organisms” C6H12O6 + 6O2 —> 6CO2 + 6H2O + ENERGY => => / How is metabolic rate measured? Heat ATP calories " consumption CO2 & production , , heat production "indirect calorimetry" or "respirometry" Direct Calorimetry Indirect Calorimetry (AKA Respirometry) Zollinger et al 2011 http://www.southdenvermedicine.com/portals/2229/ Skins/IH-SDI/images/VO2_Max_Testing.png Specific latent heat for H2O= 334 J/g  The Respiratory Quotient (RQ) Metabolic water (g) Per gram of food 0.56 1.07 0.4 - 0.5 rate of CO2 production RQ = rate of O2 consumption Varies with food type (Carbohydrates, Protein, Fat)  Catabolism and Anabolism Catabolic reactions break down complex organic compounds, providing energy Anabolic reactions synthesize complex molecules from small molecules, requiring energy Exchange of energy requires use of ATP (adenosine triphosphate) molecules http://chemwiki.ucdavis.edu/Physical_Chemistry/Thermodynamics/Case_Stu dies/Case_Study%3A_Thermodynamics_of_ATP  ATP’s Central Role in Metabolism D curbom Each cell has about 1 billion ATP molecules (equals ~2 sec of max contraction for skeletal muscle); rapid ADP‐ATP turnover. Over half of the energy released from ATP is lost as heat.  Energy Transfer Energy is found in the bonds between atoms. Oxidation is a decrease in the energy content of a molecule: electrons are lost, plus H+. Reduction is the increase in the energy content of a molecule: electrons gained, plus H+. Oxidation‐reduction reactions are always coupled within the body. – sometimes an intermediate molecule is involved in the electron transfer: coenzyme (NAD + and FADH) *NADH and FADH2….  4 Steps of Glucose Catabolism: 1. Glycolysis 2. Formation of Acetyl Coenzyme A 3. Krebs Cycle 4. Electron Transport Chain (ETC) Overview of Glucose Catabolism 1 Glucose + 6 O2 –> 6 CO2 + 6 H2O + energy (used to generate 36‐38 ATP)  glucose ATP] 62 ↓+ Glycolysis He 31 Pyruva - Co2 ↓ - NADH 2 artyl coA Jacety formation Oxygen ↓ EAT NADH chain" electron transport " Oxidative Phosphorylation The Electron Transport Chain = a series of integral membrane protein complexes in the inner mitochondrial membrane. The ETC is capable of oxidation/reduction (donating/receiving electrons). The small amounts of energy released w/each transfer is used to make an H+ gradient. The H+ gradient is used to form ATP; this process is called chemiosmosis. Summary of (aerobic) Cellular Respiration In the presence of O2, glucose is completely broken down (i.e., oxidized) into: CO2, H2O, & high‐energy electrons. High energy electrons are used by the ETC to pump H+ ions, which are used to make ATP (via chemiosmosis). CO2, H2O, & ATP move out of the mitochondria into the cytoplasm.  The Manifold Functions of the Liver * Metabolism & storage of carbohydrates, proteins & lipids Detoxifies blood by removing or altering drugs & hormones (thyroid & estrogen) Removes bilirubin (waste product of red blood cell breakdown) Releases bile salts to help digestion by emulsification of lipids Stores fat‐soluble vitamins (A, D3, E, K) Stores iron, copper and vitamin B12 Phagocytosis of worn out blood cells and bacteria Plays a role in vitamin D activation Digestive function of liver in green Metabolic functions of liver in blue  Overview of Glucose Metabolism Glycolysis (break down of glucose) – Glucose to pyruvate/lactate Glycogenolysis (break down of glycogen) – Glycogen to glucose Glycogenesis (formation of glycogen) – Glucose to glycogen Gluconeogenesis (formation of new glucose) – Other substrates to glucose glycogen Gaine Glycogenesis vs. Glycogenolysis Glycolysis vs. Gluconeogenesis  Transport of Lipids by Lipoproteins Most lipids are nonpolar and must be combined with protein to be transported in blood Lipoproteins are spheres containing hundreds of molecules Lipoproteins are categorized by function & density. 4 major classes: – chylomicrons – VLDLs HDL = high density (of protein) lipoprotein – LDLs – HDLs LDL = low density (of protein) lipoprotein VLDL = very low density (of protein) lipoprotein  Fate of Lipids Oxidized to produce ATP Excess stored in adipose tissue or liver Synthesize structural or other important molecules – phospholipids of plasma membranes – lipoproteins that transport cholesterol – thromboplastin* for blood clotting – myelin sheaths to speed up nerve conduction – cholesterol used to synthesize bile salts & steroid hormones thromboplastin = phospholipids + tissue factor (both needed to activate extrinsic blood clotting pathway)  TG Lipogenic feypoglusin Gluconeogenis Glucose FA + Glycra lipogenisis Overview of Lipid Metabolism Promo Refere bodies Lipolysis: triglycerides are broken down into glycerol and fatty acids w/in liver or adipose cells in the presence of epinephrine, norepinephrine, cortisol Beta oxidation: fatty acids are broken down to produce acetyl co‐A Lipogenesis: triglycerides are synthesized from amino acids or glucose w/in liver or adipose cells in the presence of insulin; fatty acids and glycerol are synthesized from acetyl coA (FA) and glucose (glycerol).  Lipolysis Fatty acids undergo beta oxidation in mitochondria to produce acetyl CoA and lots of ATP Ketogenesis occurs in liver cells; ketone bodies are used by heart muscle & kidney cortex for ATP production  Lipogenesis Fuel sources for lipogenesis include: ‐ amino acids, glycolysis metabolites, and ketone bodies for fatty acid production from acetyl‐CoA ‐ glycolysis metabolites for glycerol production  Fate of Proteins Proteins are broken down into amino acids, which are transported to the liver Amino acids may be – deaminated to enter Krebs Cycle – donate amino group to form new amino acids (transamination) – used to synthesize new proteins throughout the body Excess amino acids may be converted into glucose or triglycerides (no storage) Absorption of amino acids into body cells is stimulated by insulin‐like growth factors (IGFs) & insulin  Metabolic Functions of the Liver – Part 1 Carbohydrate Metabolism Lipid Metabolism Turn amino acids into glucose ‐ Synthesize cholesterol gluconeogenesis Synthesize lipoproteins, (e.g. HDL and LDL) which Turn triglycerides into glucose ‐ are used to transport fatty gluconeogenesis acids and cholesterol in the Turn excess glucose into glycogen bloodstream & store in the liver ‐ glycogenesis Store some fat ‐ lipogenesis Turn glycogen back into glucose Break down some fatty as needed ‐ glycogenolysis acids – beta oxidation seris oxidation =Acetyl-CoA lipeosis Metabolic Functions of the Liver – Part 2 Protein Metabolism Deamination: removal of an amine group from an aa carbon skeleton used to make ATP resulting toxic ammonia (NH3) converted into urea, which is excreted by the kidney Transamination: transfer of an amine group converts one amino acid into another synthesizes plasma proteins utilized in the clotting mechanism and immune system  absorptive state = the time after a meal when nutrients enter the blood and need to be stored Absorptive State  Metabolism during Absorptive State The absorptive state represents the time after a meal when nutrients enter the blood and need to be stored. The hepatic portal system is used for absorption of glucose and amino acids. The liver is able to act on these first. Lacteals are used for absorption of dietary fats which are transported as lipoproteins through the lymphatic system before reaching general circulation.  Absorptive State Summary Storage of excess fuels occurs in hepatocytes, adipocytes, skeletal muscle Most glucose entering liver cells is converted to glycogen (10%) or triglycerides (40%) Dietary lipids are stored in adipose tissue Amino acids are deaminated to enter Krebs cycle, or are converted to glucose or fatty acids Amino acids not taken up by hepatocytes are used by other cells for synthesis of proteins post absorptive state = the time after a meal when absorption of all nutrients is complete (usually ~4 hrs) Postabsorptive State Metabolism During Postabsorptive State 4 hours after a meal when absorption of all nutrients is complete (similar to starvation) Maintaining normal blood glucose level (70 to 110 mg/dL of blood) is major challenge  goal is to put glucose back into the blood or use alternative fuel sources  Postabsorptive State Summary Glucose (enters blood from the liver) – glycogenolysis – gluconeogenesis glycerol from adipose tissue amino acids and lactic acid from muscle Alternative fuel sources: – fatty acids fed into Krebs as acetyl CoA for most cells* – oxidation of ketone bodies by heart & kidney *Most body cells switch to utilizing fatty acids; brain still prefers glucose.