metabolism in fed and starved states Flashcards
what is the metabolism
the feed-fast cycle
Human metabolism oscillates between fed and fasting
The switch determines metabolic changes in the molar ratio of insulin to glucagon in blood
what is a fed state
during meals and several hours after, high insulin and low glucagon (high I to G ratio)
what is a fasting state
6-12 hours after a meal
Low insulin and high glucagon (low ratio), lasts in excess of 12 hours is prolonged fasting or starvation
Changes in metabolism from absorptive to post-absorptive state
Absorptive products of digestion (proteins, TG, glycogen) stored, mobilised in post absorptive in body cells
absorptive turns glucoses to glycogen, triglyceride and AA, in post-absorptive its turned back to glucose in liver
Metabolism in fed state
Food intake stimulates insulin release, inhibits glucagon secretion
Affects metabolism in liver, muscle and adipose tissue
Utilisation in brain unchanged
Metabolism in the liver in fed state
High conc of nutrients lead to increase in I G ratio
High blood glucose means it enters the liver and is converted to glycogen and TGs
Glycerol from peripheral tissues is converted to TAGc
Excess AAs converted to pyruvate for TCA cycle for energy or converted to TAGs
metabolism in muscle in a fed state
Glucose enters via insulin-stimulated Glut 4 transport system and converted to glycogen or metabolised via glycolysis and TCA
Fatty acids enter both from diet via chylomicrons and from liver via VLDL. Oxidised via B-oxidation to acetyl CoA to product ATP for contraction
AAs incorporated into proteins
metabolism in adipose in a fed state
Glucose enters via insulin dependant Glut 4 transport system – converted via glycolysis and PDH into acetyl-CoA then FAS and TAGs FAs enter from VLDL and chylomicrons, converted to TAG Glycerol released from TGs returned to liver for reuse LPL activity (C and VLDL in and glycerol out) increased and HSL activity inhibited by insulin
metabolism in the brain in a fed state
Takes up glucose via glut 1 and 3 transporters and metabolises it oxidatively by glycolysis and TCA cycle to produce ATP
what happens in early fasting
Liver switches from glucose utilising to glucose producing
Decrease in glycogen synthesis and increase in glycogenolysis
Gluconeogenesis
what happens in the liver in early fasting
Plasma glucose falls so no longer enters liver via glut 2 (low affinity), liver changes from a user to exporter of glucose
Reduced ratio activates glycogenolysis and gluconeogenesis (from lactate and alanine) via cAMP production in response to glucagon
Protein in liver and other tissues broken down to AAs to fuel gluconeogenesis
Fatty acids from lipolysis used to produce energy via B oxidation, citrate and acetyl-CoA produced from oxidation of fatty acids activate gluconeogenesis and inhibit glycolysis
what happens in the muscle in early fasting
The fall in insulin reduces glucose entry, glycogenolysis doesn’t occur as no glucagon receptors in skeletal muscle so no activation
Muscle and other peripheral tissues switch to fatty acid oxidation as source of energy which inhibits glycolysis and glucose utilisation to preserve glucose
Proteins broken down to AAs and carbon skeletons can be used for energy or exported to liver in form of alanine
what happens in adipose tissue in early fasting
Glut 4
Mobilise TGs in response to reduced ratio and activate sympathetic NS by releasing NA
Some FAs are used directly within tissue to produce energy, remainder released into bloodstream to support glucose independent energy production in muscle and other tissues
Glycerol cannot be metabolised and us recycled to liver to support gluconeogenesis
what happens in the brain in early fasting
Continues to take up glucose – high affinity of glut 1 ad glut 3 and independence from insulin
Glucose continues to be metabolised as brain cannot switch to fatty acids as free fatty acids don’t cross blood brain barrier
what is a starved state
Chronic low insulin and high glucagon
Accompanied by decrease in conc of thyroid hormones to dec metabolic rate
Free FAs major energy source
Produce ketone bodies as alternative fuel source
what happens in the liver in a starved state
No glucose enters liver and glycogen stores depleted after 24 hours
Plasma glucose dependant on gluconeogenesis from lactate, glycerol and alanine from fat and protein. Kidney also becomes important source of gluconeogenesis
Urea synthesis stimulated to cope with increasing amino groups entering liver
Glycogen synthesis and glycolysis inhibited
FAs enter the liver and provide energy to support gluconeogenesis and excess acetyl-CoA converted to KBs (acetoacetate and B-hydroxybutyrate). Not used by liver but released for oxidation by other tissues
what happens in muscle in a starved state
Little glucose entry – FAs as fuel
KBs taken up by muscle and other peripheral tissues and used as further source of fuel in heart and muscle to conserve glucose
KBs reduce proteolysis and decrease muscle wasting
FA oxidation supplies energy for contraction
what happens in adipose in a starved state
Glut 4
Uses FAs from TAG to supply all energetic needs of major tissues
Lipolysis greatly activated because of low ratio and blood levels of FAs rise 10 fold
Glycerol exported to liver to be converted to glucose
what happens in the brain in a starved state
Levels of KBs rise in plasma so can cross blood brain barrier and enter brain as source of energy sparing use of glucose but can’t completely replace glucose so continues to take some up and metabolise by glycolysis – net glucose synthesis during starvation essential
what is the glucose-fatty acid cycle
Mobilisation of fatty acids in response to glucagon or adrenaline increases FA oxidation to acetyl-CoA in peripheral tissues
Excess ACoA converted to citrate in TCA cycle which builds up in cytoplasm and inhibits PFK-1
Build-up of G6P inhibits hexokinase and prevents glucose phosphorylation
Increase in glucose prevents further glucose entry to conserve glucose
Glucose utilisation in various metabolic states
Fed state – glucose provided by diet
Fasted state – most glucose from breakdown of liver glycogen
Starved state – most glucose from gluconeogenesis, breakdown of fats and proteins for amino acids and glycerol as substrates
how is glycogenesis and glycogen synthesis controlled
hormonal
enzymes subject to allosteric control
enzymes also subject to hormonal control - glucagon, adrenaline, cortisol and insulin
Hormonal control mediated by changes in phosphorylation
source initiator and effect of glucagon
pancreatic a cells
hypoglycaemia
rapid activation of glycolysis and glycogen synthesis (release glycogen from liver)
source initiator and effect of adrenaline
adrenal medulla
hypoglycaemia, stress
rapid activation of glycolysis and glycogen synthesis (release glycogen from liver)
support muscle contraction
source initiator and effect of cortisol
adrenal cortex
stress
chronic activation of glycolysis and glycogen synthesis
source initiator and effect of insulin
pancreatic B cells
hyperglycaemia
inactivation of glycolysis and glycogen synthesis (increases in blood glucose to promote its oxidation, glycogen synthesis and TG synthesis)
Reciprocal regulation of phosphorylase and glycogen synthase by phosphorylation
Glucagon and adrenaline increase cAMP production and activate cAMP PK
This phosphorylates glycogen synthase, inactivates it
phosphorylates phosphorylase kinase to activate it, so it can phosphorylate glycogen
Phosphorylates phosphorylase to activate it so glycogen is degraded and simultaneously inhibit glycogen synthesis
Phos kinase can be activated allosterically by Ca2+ ions linking to contraction and glycogen breakdown to ensure adequate ATP
Insulin activates protein phosphatase-1 which removes phosphates
Switches off glycogen breakdown and switches on glycogen synthesis
Glycogen metabolism in liver and muscle
Glucagon stimulates glycogenolysis in liver, 2nd messenger cAMP
Adrenaline stimulates glycogenolysis in muscle and liver via B-adrenergic receptors (2nd messenger cAMP) and in liver via a1-adrenergic receptors (2nd messenger Ca2+)
Insulin stimulates glycogen synthesis in both tissues
