PGY452 552 Endocrine physiology 5 Quick overview of whole body metabolism A Food to energy B 3 sources of energyIN in 4 organs C Metabolic pathways D Integration of metabolism Why bother with metabolism Specialized roles of tissues Time H H H H H H Hormone H Response Metabolic control is the major function of the endocrine system Common view of metabolism Not relevant to complex organisms Does not account for Input H H H H Response 2 I don t care if you know metabolism Emphasize The names of the pathways Substrates start products Each pathway s role in physiology Anabolic vs catabolic Characteristic of fed or fasted state Tissue specificity This will allow us to focus on endocrine control 3 Most energy in is stored Short term storage carbohydrates Proteins Fats FOOD Membrane transport Signal transduction Detoxification degradation Short long term storage fats Metabolism Synthetic reactions Energy in Carbohydrates Energy out Thermogenesis Involuntary movement Voluntary movement Excess 4 Average energy out 2300 kcal day Basel metabolic rate BMR Minimum expenditure for normal biochemistry 1400 kcal day 1 kcal min Variability in Eout 1 2 3 4 5 6 Age Sex Energy intake Lean muscle mass Genetics physiology Voluntary movement Average person 70 kg 150 pounds Major source of variability 5 Whole body metabolism balance between anabolism catabolism Anabolism Catabolism Large molecules Energy Energy mobilizaton mobilizaton Energy Energy storage storage Large molecules Small molecules Small molecules Fed state Fasting state absorptive post absorptive 6 Molecules of energy storage and utilization Catabolism Anabolism Storage Usage Proteins Glycogen Triacylglycerols Amino acids Glucos e Nonesterified fatty acids ENERGY ATP 7 The difference between anabolism and catabolism is confusing Easy way to tell for our purposes INSULIN ANABOLISM We will get to that next 8 Molecules of anabolism Glycogen Highest metabolic priority Stores short lived 4 kcal g 1500 kcal total Triacylglycerols TAGs fats Dietary fats Anabolism from glucose Proteins 25 of energy stores Mobilizable 4 kcal g Other major roles From 60 70 of energy stores Lipid droplets At 9 kcal g that s 100 000 kcal 9 Carbohydrate metabolism Glucose transporter Glycogen Glucose 6Phosphate Glycogenesis glucose g 6 P glycogen Glycogenolysis glycogen g 6 p glucose Glycolysis ATP catabolic no endocrine control Nonesterified fatty acid synthesis anabolic endocrine control Glucose NEFA Glycolysis 6 carbon ATP Citrate ATP 3 carbon Citric acid cycle Pyruvate Acetyl CoA O2 Electron transport system 10 Lipid metabolism lipolysis lipogenesis Lipogenesis glucose or cytoplasmic acetyl CoA NEFA TAG Lipolysis TAG NEFA Lipid Droplet 2 TAG LPL Lipoprotein lipase 5 4 1 Glycolysis 3 Ac CoA Pyruvate NEFA Glycerol Citric acid cycle Citrate Acetyl CoA 11 Lipid metabolism 1 As covered previously de novo synthesis of NEFA occurs from glucose by way of glycolysis and the citric acid cycle This is lipogenesis a stricter definition would only include the cytoplasmic acetyl CoA to NEFA but that doesn t help with the physiology of the process so I m not going to make the distinction 2 Lipoproteins called Chylomicrons or VLDL covered on slide carry triacylglycerol TAG in the ECF The TAG are de esterified by lipoprotein lipase LPL to diacylglycerol not shown then to non esterified fatty acids NEFA 3 moles 1 mole glycerol per mole TAG 3 Depending on metabolic state glycerol can be converted to pyruvate in the 3 carbon phase of glycolysis or glycolysis can produce the glycerol necessary for TAG synthesis 4 In the cell NEFA and glycerol are condensed to form TAG which are stored in lipid droplets Cells to not store TAG directly it must first be converted to NEFA This is also part of lipogenesis 5 Mobilization of lipid droplet TAG occurs through lipolysis Most tissues that release lipids do so as NEFA 12 Glucose is produced in the LIVER by gluconeogenesis Requires ENERGY Requires ENERGY and CARBON atoms Gluconeogenesis oxidation ATP 4 CAcT Electron transport system ATP NEFA 1 2 Pyruvate Amino acids CoA Citric acid cycle NH3 NH3 O2 3 Ketone Bodies O Ac CoA 5 13 Glucose is produced in the liver by gluconeogenesis 1 Gluconeogenesis requires energy This energy must come from non esterified fatty acids 2 The NEFAs are imported into the mitochondria acylated and conjugated with CoA by the carnitine acylcarnitine transferase complex The fatty acylated CoA molecule is then oxidized two carbons at a time providing substrate for the citric acid cycle resulting in generation of ATP This process is called oxidaton of NEFA 3 Carbon atoms to make pyruvate are provided by amino acids Some amino acids are directly converted to pyruvate others must be converted in the citric acid cycle 4 Gluconeogenesis is the conversion of pyruvate to glucose 6 phosphate with input of ATP from oxidation of NEFA 5 Lack of coenzyme A can leave oxidation incomplete causing a build up of ketone bodies More specifically acetone acetoacetic acid and hydroxybutyric acid 14 Lipid transport storage Hydrophobic Stored as triglycerides in lipid droplets inside cells Need carrier proteins in blood Chylomicrons FED Very low density lipoproteins FED Albumin FASTED GI Liver NEFA TA G VLDL Blood TA G NEFA Albumin Chylomicrons NEFA TA G TA G Muscle TA G Adipose 15 Tissue metabolism is specialized Users Brain CNS Givers Requires glucose Highest priority Skeletal muscle Biggest glucose user up to 75 OF THE TOTAL Uses fats at rest Stores for own use Liver Stores makes glucose Supplies CNS Glucose to fats for storage Adipose Fat storage site Comes from excess Lipids Glucose 16 Fed state metabolism Storage rules Muscle TAG NEFA ATP NEFA Pyruvate Liver Ac CoA Ac CoA Pyruvate TA G os oxph VLDL LPL CM NEFA Adipose TA G 17 Fed State Metabolism Storage Rules In the fed state there are plenty of glucose fats from chylomicrons CM available Liver storage conversion o Glucose Glycogen 20 o Extra Glucose NEFA TAGs o TAGs VLDL Adipose Adipose major energy reserve o Chylomicrons TAGs storage o VLDL from liver TAGs storage o Extra Glucose not much TAGs storage Muscle major energy user 70 of glucose The usage pattern is a bit complex Some skeletal muscle fibers use mostly glucose for ATP production others are more dependent on oxidation for ATP and still others use both In those fibers reliant on oxidation glucose is preferentially converted to TAG Fibers that rely of glucose for ATP production will preferentially make glycogen This will be