BISC 307L 1st Edition Lecture 14 Current Lecture Flow of Molecules through metabolism o o Looks at the flow of molecules through metabolism as if it were plumbing o Top shows food molecules entering body as fats carbs and proteins o Bottom tubs are the pools in the blood plasma of the immediately available molecular components of these molecules glucose fatty acids amino acids Pools are what the body s cells use o Above the pools are the storage forms of these molecules o All cells have protein in them the ones with the most are skeletal musclethese can be broken down easiest to restore the amino acid pool o This breakdown does not disturb their function o Connecting storage pools with the immediately available pools are the actions that break these things down o Cells can take excess glucose and convert to fat type of lipogenesis o Carb store glycogen replenished by glycogenesis and broken down by glycogenolysis o Amino acids broken down by proteolysis and protein synthesis is how its replenished o Some lateral pipes Glucose can be synthesized by amino acids o Normal metabolism in those tissues area powered by fatty acids or glucose o Excess nutrients are put back in storage forms o Red lines are range of normal glucose o BRAIN Taps into glucose at a level lower than the red line which most tissues cant Importance of this ability the brain depends upon glucose more than any other tissue because it is highly metabolically active and cannot store any form of energy o All starts with you eating Control of Appetite and Satiety o o All starts with you eating In recent years there has been an explosion of research findings on the control of appetite Satiety not being hungry We must ensure that we have adequate fuel to power metabolism Control is complicated Before adipocyte is tumor necrosis factor retinol Control resides in hypothalamus The box In those nuclei there are neurons that are characterized by either 1 neuropeptide Y o Directly stimulates hunger and food intake 2 Melanocortin peptides o Decrease hunger o Family of POMC which is a precursor protein that is cleaned up into pieces that become neurotransmitters ACTH o Most important one is alpha MSH o Important in brain and digestive tract o Increases satiety 3 Agouti related protein o stimulates hunger like NP y o by antagonizing the affects of alpha MSH Regulated by fat cells Gut hormones at the bottom Ghrelin o Hunger stimulating hormone o Produced by stomach when empty o Stimulates neuropeptide Y and agouti related protein o Found that people who have recenlty lost weight even though stomach is filled ghrelin is still secreted CCK o Inhibit hunger o Stimulate aMSH o Inhibit NP Y o Full intestine after meal o Antagonistic with Ghrelin quickly PYY o Decrease hunger o Intestine not full of food but full of high calorie food fat o Inhibits NP Y o Stimulates aMSH o Antagonizes ghrelin but more long term of an effect not same time scale Top Adipocytes First to be discovered was leptin Satiety promoting hunger inhibiting hormone produced by adipocytes Stimulates aMSH and inhibits activity of other Dependent on fat content Also stimulates metabolic rate Get really fat if you are leptin deficient continue to accumulate fat without feedback inhibition of appetite Operates in the long time scale to regulate appetite Upper left Found in mice these hormones are also secreted by adipocytes 1 Tumor necrosis factor a stimulate insulin resistancereduce ability to respond to insulin o inflammatory cytokine o pro inflammatory effects 2 Retinol binding protein 4 same as 1 o retinol made in liver o transports retinol o also insulin resistance promoting hormone 3 Resistin same as 1 o was named resistin because closely correlated with the development of insulin resistance o pro inflammatory cytokine occurs in inflammatory response upstream of TNFa 4 Adiponectin o not involved in insulin resistance o stimulates the effect of insulin on muscle cells especially o anti diabetic affect o low in obese people o lean people secrete a lot of this Pancreatic Islets o o Where are the two most important hormones Pancreas Under the stomach Duodenum first part of small intestine Two hormones most important Largely antagonistic co released under most conditions 1 Glucagon post absorptive state raise blood glucose 2 Insulin major hormone of absorptive state lowers blood glucose 98 of pancreas is the exocrine pancreas which secretes alkaline secretion high in bicarbonate which neutralizes stomach juices also source of many digestive enzymes remaining 2 are the islets of langerhans that are scattered and secrete the hormones alpha and beta 1 Beta cell insulin amylin o islet amyloid polypeptide IAPP o co released with insulin o host of effects that collaborate with insulin to bring about the same overall effect o decrease gastric emptying o direct affect to increase satiety in brain o decreases digestive secretions gastric juice pancreatic enzymes and bile o inhibits glucagon secretion o slowing down digestion and absorption to lower blood glucose o amyloid can be bad form of misfolded protein and can catalyze crystallization of other cells and causes apoptosis this amylin peptide before its released it must be processed and folded in a less deadly way so amylin is not bad misfolded amylin may play a role in the development of type 2 diabetes with development of insulin resistance comes increased insulin secretion which also increases amylin secretion which causes more room for error in this important mechanism of fixing folds not processed forms amyloid plaques kills cells spreads to other cells resulting in full blown type two diabetes o 2 Alpha cell secrete glucagon outer cortex 3 Delta cells secrete somatostatin o 1 suppresses release of gastrointestinal hormones o 2 suppresses both insulin and glucagon release o 3 Slows gastric emptying decreases intestinal motility reduces blood flow to the intestine o 4 Inhibits the exocrine pancreas secretions o Seems to be shutting everything offsomatostatin suppresses body growth since digestion is necessary for growth o Opposite of growth hormone somatotropin o Also common neurotransmitter in brain and enteric nervous system has same effect in all those places o Suppresses release of GH from anterior pituitary 3