BISC 307L 2nd Edition Lecture 15 Current Lecture Metabolism and Metabolic Fuel There are two states of the body 1 you have just eaten and food is being absorbed This is the absorptive fed state when there is an excess of fuel flooding blood Also known as the anabolic state 2 Post absorptive fasted state You are not eating and catabolic reactions are predominating Flow of Molecules through Metabolism Food molecules enter the body as three major macromolecules fats carbs and protein The tubs immediately underneath them represent the immediately available pools in the blood plasma of free fatty acids glucose and amino acids The pools at the bottom are what the body cells use for their needs and just above them are the storage forms of these fuel molecules with fatty acids stored as fat glucose stored as glycogen and the amino acids stored in the body protein protein stores in the body are all the cells that have protein in them mainly skeletal muscle which can be broken down when necessary to restore the protein pool This doesn t greatly reduce their function even if you got rid of half of the protein in your skeletal muscle you would be weaker but still functional Connecting the storage pool with the immediately available pools are the systems of reactions processes that breaks one down into another Lipolysis breaks down fat to form free fatty acids Free fatty acids and excess glucose can also be esterified into new fats through lipogenesis Glycogen carbohydrate stores is replenished by glycogenesis from the glucose pool mostly down in the liver And glycogen is broken down by glycogenolysis to break glucose Amino acids are broken down by proteolysis which isn t shown Other lateral pipes exist for example gluconeogenesis glucose can be synthesized from amino acids If you take the amino group off amino acids they look like carbohydrates The liver can transmogrify those amino acids and convert them into glucose gluconeogenesis For normal metabolism in most tissues which is powered by glucose or fatty acids any excess nutrients are recycled back into their storage forms The red lines in the glucose pool represent the levels of normal plasma glucose The pipe coming out of the left can only take glucose out of the pool when glucose levels are above the lower pipeline level You can also see that the brain metabolism is privileged and it is at a lower pipeline level meaning it can continue drawing glucose even after levels have fallen down below the normal range This is because brain metabolism is so important it depends on glucose more than any other tissue CNS tissues are highly metabolically active and they do not store any form of energy there are no glycogen or fats or proteins up there for fuel Since it has such a high metabolic rate it is completely dependent on an adequate supply of glucose Control of Appetite and Satiety Satiety is the opposite of hunger This is one of the most important things we do ensure there is adequate fuel availability to power our entire metabolism Therefore the control of appetite is highly complicated Control resides in several nuclei of the hypothalamus the box is meant to represent the hypothalamic nuclei In those nuclei there are neurons that are characterized by their release of principal NT s of three types 1 Neuropeptide Y which directly stimulates hunger and eating 2 Melanocortin peptides which decrease hunger or stimulate satiety They release various melanocortin peptides What is melanocortin It is a family of peptides that are posttranslationally processed from POMC POMC is synthesized processed and cleaved The products are hormones or NT s one important one being ACTH the most important melanocortin peptide in the control of satiety is the alpha MSH or melanocyte stimulating hormone Alpha MSH released from these neurons increases satiety 3 agouti related protein which stimulates hunger Agouti is a signaling peptide that controls skin color in infants This has a homologous structure to that protein hence the name It antagonizes the effects of alpha MSH Whether you feel hungry or not is a balance between stimulatory and inhibitory influences These feeding and satiety centers in the hypothalamus are subject to complex regulation due to hormone mechanisms The hormones come from adipocyte fat cells which release the four things on the upper left and leptin The hormones at the bottom of the figure are the gut hormones or gastrointestinal hormones 1 Ghrelin a hunger stimulating hormone This is a circulating hormone that is produced by the stomach when it is empty It works by stimulating Neuropeptide Y and Agouti related protein secreting neurons in the hypothalamus But when you eat a meal ghrelin secretion drops significantly interesting fact people who are overweight have stomachs that have been habituated to being overfilled So even though their stomachs are filled they still secrete Ghrelin This may be part of the reason why people who lose weight especially rapidly have a hard time keeping it off The two hormones on the bottom right inhibit hunger They are both from the intestine and exert their effect by stimulating the neurons that decrease hunger melanocortin peptides and by inhibiting neuropeptide Y neurons which secrete NYY which stimulates hunger They are 2 CKK cholecystokinin which is secreted by the intestine after it is full after a meal The intestine also secretes the other hormone not necessarily when it is full of food but when it is full of food from a high calorie meal Secretion of 3 polypeptide YY is correlated with the caloric content of the meal and not volume whereas CCK is more related to volume An intestine full of high calorie foods like fat will cause PYY to activate and decrease hunger Ghrelin and the two hormones on the right are antagonistic but they work on different time scales Ghrelin and CCK are secreted in the same time span and exert their effects quickly so they are truly antagonistic However PYY creates a much more long term effect So PYY and CCK operate on different time scales PYY on hours 12 hours and CCK on minutes At the very top of our diagram we have adipocytes The first hormone in this whole figure that was discovered was leptin Leptin is a hunger inhibiting hormone released by adipocytes It stimulates satiety and decreases hunger by stimulating alpha MSH and inhibiting the activity of hunger promoting neurons Again a dashed line inhibit solid line stimulate Also leptin is produced by adipocytes relative