Presentation on theme: "Feed-Fast Cycle."— Presentation transcript:

1?Feed-Fast Cycle

2?CONNECTION OF PATHWAYS
ATP is the universal currency of energyATP is generated by oxidation of glucose, fatty acids, and amino acids ; common intermediate -> acetyl CoA ; electron carrier -> NADH and FADH2NADPH is major electron donor in reductive biosynthesisBiomolecules are constructed from a small set of building blocksSynthesis and degradation pathways almost always separated -> Compartmentation !!!

3?METABOLIC PROFILE OF ORGANS

4?THE LIVER AS CENTRAL PLAYER
Blood from intestine travels via hepatic portal to liver 1stLiver ideally placed to regulate fuel passage elsewhereLiver:Blood glucose levels are regulated very tightly to between 3 mM to 10 mM. Levels below 4.0 mM can compromise brain function.When levels are high, glucose is filtered out of the blood by kidneys in conjunction with loss of electrolytes and water.Liver is involved in interconversion of all types of fuels, carbs, aa’s, and FA’s.Products of digestion pass immediately to the liver where the liver uses what it requires then distributes or stores the rest depending upon signals received via soluble factors in the blood and circulating fuel levels. The liver immediately converts to glycogen nearly 1/3 of all of the glucose that passes through it immediately after a meal. Half of the remainder is converted to glycogen by muscle cells. The excess is used by other tissues.The liver also supplies fuel from its own reserves when readily available supplies are exhausted from the blood and/or other tissues.For instance, once blood glucose levels begin to drop, glucose is mobilized from glycogen in the liver. At the same time, hormones limit the use of newly available glucose to tissues that require glucose for energy such as kidney, medulla, retina, RBC’s, and parts of the brain. This is partially effected through control of blood flow. Most other tissues can obtain energy from FA oxidation and will do so. These fatty acids are mobilized from adipose tissue or immediate cellular stores.The liver can also interconvert fuels such as proteins to carbohydrates, etc.Hepatic Artery

5?KEY JUNCTIONS BETWEEN PATHWAYS

6?FIVE PHASES OF GLUCOSE HOMEOSTASIS
Absorptive Phase:Most blood (80%) arriving at liver does so through the portal vein which draws from capillary beds directly off of the intestine. The other 20% arrives from the heart directly via the hepatic artery (oxygenation).Much of the glucose is absorbed by the liver although a considerable amount reaches peripheral tissues. Muscle, and brain tissue are also well adapted to glucose uptake.About 1/3 goes to liver, 1/3 to muscle, and 1/3 to brain and remaining glucose dependent tissues (on average). Conversion to glycogen by muscle and liver can further increase the capacity of these tissues to absorb glucose should blood levels exceed immediate needs.When supply outstrips absorption capacity (rare), glucose is excreted in the urine.Hormonal Regulation of Glucose UptakeFood presence within the intestinal lumen stimulates release of hormones such as cholecystokinin and gastric inhibitory peptide that, in turn, induce pancreas b-cells to secrete insulin.The b-cells are even further stimulated to secrete insulin once higher blood glucose levels and subsequent catabolism within these cells directly stimulates the b-cells to release additional insulin. Notably,within the b-cells, glucose must be metabolized to induce insulin release; release is not signaled via receptors.Absorptive, post-absorptive, and early starvation occur sequentially over ~2 days.Intermediate, and prolonged starvation are over 38 subsequent days and beyond

7?POSTABSORPTIVE STATEINSULIN SECRETION –STIMULATED BY GLUCOSE UPTAKE

8?POSTABSORPTIVE STATE -> AFTER A MEAL

10?METABOLIC PROFILE OF ADIPOSITE TISSUE
Triacylglycerols are stored in tissue-> enormous reservoir of metabolic fuel-> needs glucose to synthesis TAG;-> glucose level determines if fatty acids are released into blood

11?METABOLIC PROFILE OF MUSCLES
Major fuels are glucose, fatty acids, and ketone bodies-> has a large storage of glycogen-> glucose is preferred fuel for burst ofactivity-> production of lactate (anaerobe)

12?METABOLIC PROFILE OF BRAIN
Glucose is fuel for human brain-> ketone bodies can replace glucose

14?MOBILIZATION AT STARVATION
Also at not treated diabetes

16?EARLY FASTING STATEBlood-glucose level drops after several hours after the meal- > decrease in insulin secretion-> rise in glucagon secretion Low blood-glucose level-> stimulates glucagon secretion of α-cells of the pancreasGlucagon:-> signals starved state-> mobilizes glycogen stores (break down)-> inhibits glycogen synthesis-> main target organ is liver-> inhibits fatty acid synthesis-> stimulates gluconeogenesis in liver-> large amount of glucose in liver released to blood stream-> maintain blood-glucose levelMuscle + Liver use fatty acids as fuel when blood-glucose level drops

17?EARLY FASTING STATE -> DURING THE NIGHT

18?LIVER FUNCTION IN THE FASTING STATE

19?PROLONGED STARVATION FIRST PRIORITY
-> provide sufficient glucose to brain and other tissues that are dependent on itSECOND PRIORITY-> preserve protein-> shift from utilization of glucose to utilization of fatty acids + ketone bodies-> mobilization of TAG in adipose tissues + gluconeogenesis by liver-> muscle shift from glucose to fatty acids as fuelAFTER 3 DAYS OF STARVATION-> liver forms large amounts of ketone bodies-> brain and heart start to use ketone bodies as fuelAFTER SEVERAL WEEKS OF STARVATION-> ketone bodies major fuel of brainAFTER DEPLETION OF TAG STORES-> proteins degradation accelerates-> death due to loss of heart, liver, and kidney function

20?PROLONGED STARVATION

21?PFKFruc.Bisphos.-?+

22?Summary:GlucoseHomeostasisDuringFasting