BSCI440 Exam 5 Chapter 22 and 23 Textbook Notes Singer Chapter 22 Metabolism and Energy Balance Metabolism The fate of an absorbed biomolecule depends on whether it is a carbohydrate protein or fat Nutrient pools are nutrients that are available for immediate use located in the plasma Plasma glucose concentration is the most closely regulated of the 3 nutrient pools because glucose is the only fuel the brain can metabolize except in starvation Metabolism gives priority to the brain Excess glucose goes into storage as glycogen glycogenesis Additional excess glucose is converted to fat lipogenesis If plasma glucose concentrations decrease the body converts glycogen to glucose glycogenolysis amino acids can be converted into glucose gluconeogenesis If homeostasis fails and plasma glucose exceeds a critical level as occurs in diabetes mellitus excess glucose is excreted in the urine renal threshold for glucose reabsorption is exceeded Low density lipoprotein LDL C bad cholesterol elevated concentrations of plasma LDL C are associated with atherosclerosis High density lipoprotein HDL C good cholesterol involved in cholesterol transport out of the plasma Homeostatic Control of Metabolism The endocrine system has primary responsibility for metabolic regulation depending on the ratio of insulin to glucagon two hormones secreted by endocrine cells of the pancreas Islets of Langerhans in the pancreas contain 1 Beta cells produce insulin 2 Alpha cells produce glucagon In the fed state when the body is absorbing nutrients insulin dominates and increases glucose oxidation glycogen synthesis fat synthesis and protein synthesis In the fasted state metabolic regulation prevents low plasma glucose concentrations hypoglycemia glucagon dominates and increases glycogenolysis gluconeogenesis and ketogenesis Insulin fed state anabolic hormone A major stimulus for insulin release is elevated plasma glucose concentrations Glucose absorbed from small intestines reaches pancreatic beta cells where it is taken up by GLUT2 transporters ATP production increases and K channels close cells depolarize voltage gated Ca2 channels open and Ca2 entry initiates exocytosis of insulin GLP 1 GIP CCK and gastrin all amplify insulin secretion Parasympathetic activity to the GI tract and pancreas increases during and following a meal input to beta cells stimulates insulin secretion Sympathetic activity inhibits insulin secretion in times of stress epinephrine and norepinephrine inhibit insulin secretion and switch metabolism to gluconeogenesis to provide extra fuel for the nervous system and skeletal muscles The primary target tissues for insulin are the liver adipose tissue and skeletal muscles Insulin increases glucose transport into most but not all insulin sensitive cells Insulin binds to receptor and activates it vesicles move to cell membrane and insert GLUT4 transporters cells take up glucose from interstitial fluid by facilitated diffusion Glucagon fasted state secreted by pancreatic alpha cells antagonistic to insulin glucagon acts when glucose concentrations are low in order to prevent hypoglycemia the liver is the primary target tissue for glucagon stimulates glycogenolysis and gluconeogenesis to increase glucose output Diabetes Mellitus Diabetes is characterized by abnormally elevated plasma glucose concentrations hyperglycemia resulting from inadequate insulin secretion abnormal target cell responsiveness or both Chronic hyperglycemia cause the complications of diabetes damage to blood vessels eyes kidneys and nervous system The severe type of diabetes is Type I diabetes mellitus a condition of insulin deficiency resulting from beta cell destruction autoimmune disease juvenile onset diabetes Type 2 diabetes mellitus is insulin resistant diabetes because usually patients have normal insulin levels A fasting plasma glucose concentration between 100 and 125 mg dL indicates pre diabetes and a fasting value greater than 125 is diagnostic for diabetes Type I Diabetes Type I diabetics are prone to ketoacidosis Since TI diabetics are insulin deficient the only treatment is insulin injections Following a meal nutrient absorption by the intestines is normal because this process is insulin independent but nutrient uptake from the blood and cellular metabolism in many tissues are insulin dependent and therefore severely diminished in the absence of insulin Lacking nutrients to metabolize cells go into fasted state metabolism Protein metabolism muscles break down proteins to make ATP amino acids converted to pyruvate and lactate and go to the liver Fat metabolism fat stores are broken down and fatty acids enter the blood for transport to liver where they are oxidized excess fatty acids are converted to ketones metabolic acids which can be used by the brain and muscles for ATP synthesis Glucose metabolism glucose remains in the blood hyperglycemia liver initiates glycogenolysis and gluconeogenesis to produce additional glucose from glycogen amino acids and glycerol and dumps into blood high osmolarity triggers ADH vasopressin secretion and thirst in an effort to conserve water Brain metabolism absence of insulin means absence of intracellular glucose makes the satiety center perceive it as starvation and allows the feeding center to increase food intake polyphagia Osmotic diuresis and polyuria hyperglycemia causes plasma glucose concentrations to exceed renal threshold for glucose glucose reabsorption in the proximal tubule becomes saturated as a result some filtered glucose is not reabsorbed and is excreted in urine glucosuria less water is reabsorbed and produces larger volume of urine polyuria Dehydration caused by osmotic diuresis loss of water leads to decreased blood volume and blood pressure this triggers secretion of vasopressin thirst an polydipsia and cardiovascular compensations Metabolic acidosis sources are anaerobic metabolism and ketone body production by liver causes increased ventilation acidification of urine and hyperkalemia Type II Diabetes Insulin resistance demonstrated by the delayed response to an ingested glucose load seen in the 2 hour oral glucose tolerance test Hyperglycemic also The liver does not have to turn to ketone production ketosis is uncommon in type II diabetics Complications include atherosclerosis neurological changes renal failure and blindness from diabetic retinopathy Treatments include changes in diet and exercise skeletal muscles do not require insulin for glucose uptake drugs