PGY452 552 Human Physiology Endocrinology Endocrine Principles V 5 Quick overview of whole body metabolism A Food to energy B 3 basic foods 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 Key point 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 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 7 Age Voluntary movement Energy intake Sex Lean muscle mass Endocrine physiology Genetics Average person 70 kg 150 pounds Movement genetics are the major source of variability of energy out 5 Whole body metabolism balance between anabolism catabolism Anabolism Catabolism Large molecules Produces energy Requires energy input 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 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 Proteins 25 of energy stores Mobilizable 4 kcal g Other major roles From Dietary fats Anabolism from glucose 60 70 of energy stores Lipid droplets At 9 kcal g that s 100 000 kcal 9 Carbohydrate metabolism Glucose transporter Glycogenesis glucose g 6 P glycogen Glycolysis Glycogen Glucose 6Phosphate ATP catabolic Nonesterified fatty acid synthesis anabolic Glucose NEFA Glycolysis 6 carbon ATP Citrate ATP 3 carbon Pyruvate Citric acid cycle Acetyl CoA O2 Electron transport system 10 Glucose is produced in the LIVER by gluconeogenesis NOT reverse glycolysis TAG oxidation Gluconeogenesis ATP 4 Electron transport system ATP Pyruvate Amino acids O2 3 Citric acid cycle CAcT CoA NEFA 1 2 O Ketone Bodies 5 11 Glucose is produced in the liver by gluconeogenesis 1 Gluconeogenesis requires energy This energy must come from nonesterified 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 converstion 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 Lipids requires specialize transport Glucose is soluble Lipids Liver VLDL Hydrophobic Need carrier proteins Apolipoproteins Stored as TAGs GI TAGs Adipose NEFAs glycerol Chylomicrons TAGs Albumin 13 Lipid metabolism oxidation was just covered Hormonesensitive lipase Lipid Droplet 1 4 Glycolysis 3 Pyruvate 2 LPL HSL 5 NEFA Glycerol Citric acid cycle Acetyl CoA Lipoprotein lipase Citrate 14 Lipid metabolism This slide leaves out oxidation 1 As covered previously de novo synthesis of NEFA occurs from glucose by way of glycolysis and the citric acid cycle 2 Chylomicrons or VLDL containing triacylglycerol 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 lipogenesis 5 Mobilization of lipid droplet TAG requires hormone sensitive lipase Most tissues that release lipids do so as NEFA This is lipolysis 15 Tissue metabolism is specialized Givers Users Brain CNS 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 Lipid Droplet Lipid Droplet ATP Lipid Droplet VLDL CM Liver Adipose 17 Fed State Metabolism Storage Rules In the fed state there are plenty of glucose fats from chylomicrons CM available Liver storage conversion Glucose Glycogen 20 Extra Glucose NEFA TAGs TAGs VLDL Adipose Adipose major energy reserve Chylomicrons TAGs storage VLDL from liver TAGs storage Extra Glucose not much TAGs storage Muscle major energy user 70 of glucose Glucose ATP Energy Glucose Glycogen Brain Glucose available so it is happy Fasting metabolism Glucose mobilization Lipid Droplet ATP oxidation Muscle Lipid Droplet Lipid Droplet ATP oxidation Liver Adipose 19 Fasting Metabolism Usage Rules Liver storage conversion Brain 1 Glycogen Glucose Brain It takes up the same amount as before FFAs for ATP amino acids Glucose FFAs ketones muscle Adipose major energy reserve TGs FFAs Liver Muscle major energy user Glycogen Glucose ATP Ketones NEFAs ATP 20 The difference glucose storage use FED Uptake 40 g Used 39 g Stored glycogen FASTING GNG Used 1g 0g 130 g 70 g 60 g 0g 0g 130 g ATP 300 g 70 g 0g 100 g max 50 g 180 g Assume glycogen depleted ATP 130 g 400 g max 10 g 10 g Lipid Droplet 0g 0g 0g 21