Flow of Molecules through metabolismLooks at the flow of molecules through metabolism as if it were plumbingTop shows food molecules entering body as fats carbs and proteinsBottom 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 useAbove the pools are the storage forms of these moleculesAll cells have protein in them- the ones with the most are skeletal muscle- these can be broken down easiest to restore the amino acid poolThis breakdown does not disturb their functionConnecting storage pools with the immediately available pools are the actions that break these things downCells can take excess glucose and convert to fat- type of lipogenesisCarb store- glycogen replenished by glycogenesis and broken down by glycogenolysisAmino acids broken down by proteolysis and protein synthesis is how its replenishedSome lateral pipes-Glucose can be synthesized by amino acidsNormal metabolism in those tissues area powered by fatty acids or glucoseExcess nutrients are put back in storage formsRed lines are range of normal glucoseBRAINTaps into glucose at a level lower than the red line which most tissues cantImportance 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 energyAll starts with you eatingControl of Appetite and SatietyAll starts with you eatingIn recent years there has been an explosion of research findings on the control of appetiteSatiety: not being hungryWe must ensure that we have adequate fuel to power metabolismControl is complicatedBefore adipocyte is tumor necrosis factor, retinolControl resides in hypothalamus- The boxIn those nuclei there are neurons that are characterized by either1. neuropeptide YDirectly stimulates hunger and food intake2. Melanocortin peptidesDecrease hungerFamily of POMC which is a precursor protein that is cleaned up into pieces that become neurotransmitters (ACTH)Most important one is alpha MSHImportant in brain and digestive tractIncreases satiety3. Agouti related proteinstimulates hunger like NP yby antagonizing the affects of alpha MSHRegulated by fat cellsGut hormones at the bottomGhrelinHunger stimulating hormoneProduced by stomach when emptyStimulates neuropeptide Y and agouti related proteinFound that people who have recenlty lost weight, even though stomach is filled ghrelin is still secretedCCKInhibit hungerStimulate aMSHInhibit NP YFull intestine- after mealAntagonistic with Ghrelin- quicklyPYYDecrease hungerIntestine not full of food but full of high calorie food (fat)Inhibits NP YStimulates aMSHAntagonizes ghrelin but more long term of an effect- not same time scaleTop: AdipocytesFirst to be discovered was leptinSatiety promoting hunger inhibiting hormone produced by adipocytesStimulates aMSH and inhibits activity of otherDependent on fat contentAlso stimulates metabolic rateGet really fat if you are leptin deficient- continue to accumulate fat without feedback inhibition of appetiteOperates in the long time scale to regulate appetiteUpper left:Found in mice these hormones are also secreted by adipocytes1. Tumor necrosis factor a (stimulate insulin resistance- reduce ability to respond to insulin)-inflammatory cytokinepro-inflammatory effects2. Retinol binding protein 4 (same as 1)retinol made in livertransports retinolalso insulin resistance promoting hormone3. Resistin (same as 1)was named resistin because closely correlated with the development of insulin resistancepro inflammatory cytokine- occurs in inflammatory response- upstream of TNFa4. Adiponectinnot involved in insulin resistancestimulates the effect of insulin on muscle cells especiallyanti-diabetic affectlow in obese peoplelean people secrete a lot of thisPancreatic IsletsWhere are the two most important hormones?PancreasUnder the stomachDuodenum first part of small intestineTwo hormones most important: Largely antagonistic, co-released under most conditions1. Glucagonpost absorptive stateraise blood glucose2. Insulinmajor hormone of absorptive statelowers blood glucose98% of pancreas is the exocrine pancreas which secretes alkaline secretion high in bicarbonate which neutralizes stomach juicesalso source of many digestive enzymesremaining 2% are the islets of langerhans that are scattered and secrete the hormones (alpha and beta)1. Beta cellinsulinamylinislet amyloid polypeptide (IAPP)co-released with insulinhost of effects that collaborate with insulin to bring about the same overall effectdecrease gastric emptyingdirect affect to increase satiety in braindecreases digestive secretions-gastric juice pancreatic enzymes and bileinhibits glucagon secretionslowing down digestion and absorption to lower blood glucoseamyloid can be badform of misfolded protein and can catalyze crystallization of other cells and causes apoptosisthis amylin peptide before its released it must be processed and folded in a less deadly way so amylin is not badmisfolded amylin may play a role in the development of type 2 diabeteswith 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 diabetes2. Alpha cellsecrete glucagonouter cortex3. Delta cellssecrete somatostatin1. suppresses release of gastrointestinal hormones2. suppresses both insulin and glucagon release3. Slows gastric emptying, decreases intestinal motility, reduces blood flow to the intestine4. Inhibits the exocrine pancreas secretionsSeems to be shutting everything off- somatostatin suppresses body growth since digestion is necessary for growthOpposite of growth hormone (somatotropin)Also common neurotransmitter in brain and enteric nervous system- has same effect in all those placesSuppresses release of GH from anterior pituitary 3BISC 307L 1st Edition Lecture 14 Current Lecture- Flow of Molecules through metabolismoo Looks at the flow of molecules through metabolism as if it were plumbing o Top shows food molecules entering body as fats carbs and proteinso 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 useo Above the pools are the