How is energy extracted from food?
via oxidation with carbon dioxide and water as the product
What are the 4 stages of energy extraction?
1. metabolic fuels are hydrolyzed in the GI tract to glucose, amino acids, and fatty acids and absorbed
2. building blocks degraded by various pathways in tissues to common metabolic intermediate=acetyl CoA
--energy in chemical bonds of acetyl-CoA and reducing NAD to NADH and FAD to FADH2
3. citric acid cycle oxidizes acetyl-CoA to CO2
--energy released is conserved by reducing NAD to NADH and FAD to FADH2
4. oxidative phosphorylation: energy of NADH and FADH2 is released via ETC anx used by ATP synthase to make ATP
What is the difference between type I and type II diabetes?
type I: beta cells don't secrete enough insulin
type II: insulin receptor problem
--in obesity, there's not enough of the insulin receptor put on the membrane
When do glucose levels peak and reach normal after a meal?
reach max at 45 minutes
back to normal at 90 minutes
normal concentration of glucose = 5 mM
How do glucose levels go back to normal?
inuslin and insulin independent cells (brain and erythrocytes)
What is the general pathway of extracting energy from metabolic fuels?
How is energy stored in the cell?
1) ATP: circulating form of energy; formed in catabolic pathways by phosphorylation of ADP
2) excess energy from diet is stored as fatty acids--reduced polymer of acetyl-CoA-- and glycogen--polymer of glucose
3) proteins can also be mobilized for energy in prolonged fast
What is insulin and what are it's target tissues?
anabolic hormone that promotes fuel storage
opposed by glucagon and epinephrine, cortisol, and growth hormone
--liver, muscle and adipose tissue
What is glucagon and what are it's target tissues ?
responds rapidly to decreased blood glucose levels
--promotes synthesis and release of glucose into circulation
--target tissues= skeletal muscle, adipose tissue and liver
How are anabolic and catabolic pathways controlled?
1) allosteric inhibitors and activators of rate limiting enzymes
2) control of gene expression by insulin and glucagon
3) phsophorylation (glucagon) and dephosphorylation (insulin) of rate limiting enzymes
What happens during well-fed (absorptive) states?
immediately after a meal:
-blood glucose level rises and stimulates the release of insulin
-insulin promotes glycogen synthesis in liver and muscle
-after glycogen stores are full, liver converts excess glucose to fatty acids and triglycerides
-insulin promotes triglyceride syntehsis in adipose tissue and protein synthesis in muscle
--insulin promotes glucose entry into adipose tissue and muscle
--most energy needs of liver met by oxidative of excess amino acids
--brain and RBC are insenstiive to insulin; derive energy from oxidizing glucose to CO2 and water in well fed and normal fasting states
What energy do red blood cells utilize?
under all conditions, red blood cells use glucose anaerobically for all energy needs
What happens during postabsorptive states?
-glucagon and epinephrine levels rise during overnight fast
--in liver, glycogen degradation and release of glucose into blood are stimulated by glucagon
--hepatic gluconeogenesis is stimulated by glucagon; slower than glycogenolysis
--release of amino acids from skeletal muscle and fatty acids from adipose tissue stiulated by decrease in insulin and increase in epinephrine
--amino acids and faty acids are taken up by liver, where amino acids provide carbon skeletons and oxidation of fatty acids provide ATP necessary for gluconeogenesis
How is glucose transported?
polar so can't enter cell by itself so uses GLUT transporters
--GLUT1,3: low Km, zero order kinetics; enters at steady pace; red blood cell and brain
--GLUT2: high Km, 1st order kinetics; liver
--insulin turns on GLUT4 at hormone level (via PI3K) in muscle and fat cells--insulin increases Vmax of GLUT4
--AMP actvated kinase only turns on GLUT4 in muscle
--as ATP decreases in muscle, AMP tells GLUT4 to go to the membrane
How are triglycerides transported?
can't go through membrane becuase nonpolar
--so LPL is an enzyme in the adipose tissue membrane that breaks it down to fatty acid and glycerol
--insulin turns on LPL at gene level
How do you know if someone is starving?
increased levels of alanine in the bloodstream
What is glucose sparing?
keton bodies converted to acetyl-CoA and blood glucose breakdown because RBC can only use glucose as fuel
What is the difference between muscle and liver during postabsorptive states?
muscle breakdown glycogen for itself
liver breakdowns glycogen for other organs
What happens when glycogen stores run out during postabsorptive states?
liver turn ons gluconeogenesis
source of C=lactate/pyruvate
dominant=glucogenic AA--most protein in muscle; glycerol
What is the function of HSL during postabsorptive states?
converts fat t oglycerol
becuase only the liver can deal with glycerol
How many kcal/g are the major energy sources?
Ketone bodies, carbohydrates, protein=4 kcal/gm
fat= 9 kcal/gm
alcohol = 7 kcal/gm
How much of the energy sources should you have each day?
200 kcal diet
58% carbohydrate (1,218 kcal; 305 g)
12% protein (252 kcal; 63 g)
30% fat (630 kcal; 70 g)
What happens during a prolonged fast (starvation)?
glucagon and epinephrine elevated
--lipolysis: rapid, results in excess acetyl-CoA that is used for ketone synthesis
--thus, levels of lipids and ketones increased in blood
--muscle uses fatty acids as major fuel
--brain adapts to using ketones for some of its energy needs (2/3)
--which diminishes amount of protein that needs to be degraded to support gluconeogenesis
--no energy storage form for protein (becuase each protein has specific function)
--RBC (and renal medullary cells): have few, if any, mitochondria so depend on glucose for energy
What are the preferred fuels in well fed and fasting states in the organs?
What is the role of the liver in energy metabolism?
maintain a constant level of blood glucose and to synthesize ketones when excess fatty acids are being oxidized
AFTER A MEAL: liver extracts excess glucose and uses it to replenish glycogen stores; remaining is converted to acetyl CoA and used for fatty acid syntehsis
INSULIN: stimulates glycogen syntehsis and fatty acid synthesis in the liver after a meal
fatty acids converted to triglycerides and released into blood as VLDL
WELL FED: most of energy is derived from oxidation of excess amino acids
BETWEEN MEALS; PROLONGED FAST: liver releases glucose
increase in glucagon: promotes glycogen degradation and gluconeogensis
lactate, glycerol, and amino acids provide carbon skeleton for glucose synthesis
What is the role of adipose tisuse in energy metabolism?
AFTER A MEAL: elevated insulin sitmulates glucose uptake by adipose tissue
insulin stimulates fatty acid release from VLDL and chylomicron triglycerides
lipoprotien lipase: enzyme in capillary bed is induced by insulin
fatty acids released from lipoportiens are taken up by adipose tissue and re-esterified to tiglyceride for storage
glycerol phosphate required for triglyceride syntehsis comes from glucose metabolized in adipocytes
insulin: suppress released of fatty acids from adipocytes
FASTING STATE: decrease in insulin; increase in epinephrine activates hormone sensitive lipase in fat cells--fatty acids released into circulation
What is the role of resting skeletal muscle in energy metabolism?
major fuelds: glucose and fatty acids
major consumer of fuel
AFTER MEAL: insulin causes skeletal muscle to take up glucose to replenish glycogen stores and amino acids are used for protein syntehsis
--excess glucose and amino acids acna be oxidized for energy
FASTING STATE: resting muscle uses fatty acids derived from free fatty acids in blood
--ketones may be used if fasting state is prolonged
What is the role of active skeletal muscle in energy metabolism?
stores of glycogen and some trilycerides
blood glucose and free fatty acids can also be used
FAST TWITCH: high capacity for anaerobic glycolysis; quick to fatigue
SLOW TWITCH: well vascularized and primarily oxidative
short bursts of high intesnsity exercise are supported by anaerobic glycosis drawing on stored muscle glycogen
moderately high, continuous exercise, oxidation of glucose and fatty acids are important
after 1-3 hours of continuous exercise: muscle glycogen stores depleted and intesnity of exercise decline to rate that can be suported by oxidation of fatty acids
What is the role of cardiac muscle in energy metabolism?
fetal life cardiac muscle: glucose as energy source
postnatal period: beta oxidation of fatty acids
--ketones present during prolonged fasting are also used
--failing heart: glucose oxidation increases and beta-oxidation falls
What is the role of brain in energy metabolism?
glucose is primary fuel
glucose uptake into brain via GLUT1 and 3 transproters
glycogen levels in brain are minor; normal function depends on continuous glucose supply from bloodstream
hypoglycemic donition: hyptehalamus sense fall in blood glucose level and release of glucagon and epinephrine are triggered
--fatyt acids can't cross BBB so not used
BETWEEN MEALS: brain relies on blood glucose supplied by hepatic glycogenolysis or gluconeogenesis
PROLONGED FAST: brain gains capacity to use ketones for energy