Overview of Energy Metabolism (Biochem Ch 11) Flashcards
Overview of Energy Metabolism
- hydrolysis and absorption
- conversion to Acetyl CoA and reduction of NAD and FAD
- TCA: Acetyl CoA to Co2, and reduction of NAD and FAD
- Oxidative Phosphorylation; ETC: NADH/FADH energy released. Produces ATP. Requires O2
- fuels are hydrolyzed in the GIT tract and absorbed
- fuels degraded in various pathways to common intermediate Acetyl CoA.
- most energy from fuels contained in chemical bonds of Acetyl CoA
- a smaller portion of energy is concerned in reducing FAD to FADH2 - TCA cycle oxidizes Acetyl CoA to CO2
- energy released in this process is converted by reducing NAD to NADH or FAD to FADH2 - Oxidative Phosphorylation releases energy in NADH and FADH2 via ETC and used to product ATP
- requires O2
Carbohydrates are converted to?
Carbohydrates –> Glucose –> Pyruvate –> Acetyl CoA –> TCA cycle
Protein is converted to?
Protein –> AA –> –> Acetyl CoA –> TCA
or
Protein –> AA –> –> Pyruvate –> Acetyl CoA –> TCA
Fat is converted to?
Fat –> Fatty Acids –> Acetyl Coa (via beta oxidation)
_____ is the final common product of sugar, protein, and fat metabolism
Acetyl CoA (which then goes into the TCA cycle)
___ is a polymer of glucose
glycogen
Half of the energy from metabolic fuels is captured as ATP, the rest is ____
Half of the energy from metabolic fuels is captured as ATP, the rest is given off as heat
- Insulin is an anabolic hormone that promotes _____
- it is opposed by:
- Insulin is an anabolic hormone that promotes fuel storage
- opposed by:
- glucagon
- epinephrine
- cortisol
- growth hormone
There is a limited amount of ATP in circulation. Most of the excess energy from the diet is stored as ____
- There is a limited amount of ATP in circulation. Most of the excess energy from the diet is stored as FATTY ACIDS and GLYCOGEN (a polymer of glucose)
- FA = a reduced polymer of acetyl CoA
- Glycogen = a polymer of glucose
Cholesterol is required for
- membrane structure
- proteins for muscle contraction
- polysaccharides for the ICM
The major function of glucagon is to
respond rapidly to decreased blood glucose levels by promoting:
- the synthesis and
- release of glucose into circulation
Anabolic and catabolic pathways are controlled at 3 important levels:
- allosteric inhibitors and activators of rate-limiting enzymes
- control fo gerne expression by insulin and glucagon
- phosphorylation (glucaon) and dephosphorylation (insulin) of rate-limiting enzymes
3 major tissues for insulin are:
- liver
- muscle
- adipose tissue
insulin promotes
- glycogen synthesis in the liver and muscle
- after the glycogen stores are filled, the liver converts excess glucose to fatty acids and triglycerides
- insulin promotes TG synthesis in adipose tissue and protein synthesis in muscle
- as well as glucose entry into both tissues
After a meal, most of the energy needs of the liver are met by _____
the oxidation of excess AA
Immediately after a meal….
blood glucose levels rise and stimulate the release of insulin
Tissues insensitive to insulin (aka are insulin independent)
- brain and RBC
brain and other nerves derive energy from
- oxidizing glucose to CO2 and water in both the well-fed and normal fasting states
- only in prolonged fasting does this situation change
- in a fast, the liver pumps as much glucose into the blood stream as possible for the brain and RBC
Under all conditions, RBC use _____ for all their energy needs
Under all conditions, RBC use glucose anaerobically for all their energy needs
_____ levels rise during an overnight fast
- Glucagon and epinephrine levels rise during an overnight fast
- these hormones exert their effects on skeletal muscle, adipose tissue, and liver
In response to fasting…
- glucagon and epinephrine levels rise
- in liver, glycogen degradation (glycogenolysis) and the release of glucose into the blood are stimulated
- hepatic gluconeogenesis is also stimulated by glucagon, but the response is slower than that of glycogenolysis
- the release of AA from skeletal muscle and FA from adipose tissue are both stimulated by:
- the decrease in insulin and
- by an increase in epinephrine - the AA and FA are taken up by the liver, where:
- the AA provide carbon skeletons and
- the oxidation of FA provides the ATP necessary for gluconeogenesis
Glucagon effects:
- phosphorylation of enzymes
- gene expression
- allosteric inhibition, activation
Why don’t RBC do the TCA cycle or ETC?
bc they don’t have mitochondria
where are FA made?
FA are made in the liver and moved to the adipose tissue
What stimulates lipoprotein lipase?
insulin
the release of AA from skeletal muscle and FA from adipose tissue are both stimulated by ……
the release of AA from skeletal muscle and FA from adipose tissue are both stimulated by:
- the decrease in insulin and
- by an increase in epinephrine
Adipose cells get glycerol to make ___
Adipose cells get glycerol to make TG from glycolysis
Which GLUT Transporter is found in muscle?
- what stimulates it?
- GLUT4
- skeletal muscle is on our 4 limbs, where GLUT4 transporters are (on muscle)
- it is stimulated by insulin and exercise
In a fast, _______ are giving carbons to the liver to make glucose, so the brain and RBC can function properly
In a fast…muscle, RBC and fat are giving carbons to the liver to make glucose, so the brain and RBC can function properly
Which GLUT transporter is found in RBC?
- GLUT 1 and GLUT 3
- work via zero-order kinetics
Which tissues are insulin-dependent?
adipose, skeletal muscle, and liver are all insulin-dependent tissues
what are ketone bodies
- alternate energy source for muscle and acetyl CoA in brain
- seen after fasting for 1 week or during DKA
Which GLUT transporter is found in liver?
- Glut 2
- it works via first order kinetics
Carbohydrates have how many kcal/gm?
Carbohydrate = 4 kcal/gm
Preferred fuels in the well-fed and fasting states:
- Liver
- Well-fed: Glucose and AA
- Fasting: FA
Preferred fuels in the well-fed and fasting states:
- RBC
- Well-Fed: Glucose
- Fasting: Glucose
Protein has how many kcal/gm?
Protein = 4 kcal/gm
Preferred fuels in the well-fed and fasting states:
- Resting skeletal muscle
- Well-Fed: Glucose
- Fasting: FA (derived from FFA in the blood), Ketones
- skeletal muscle = body’s major consumer of fuel bc of its enormous bulk
Fat has how many kcal/gm?
- Fat = 9 kcal/gm
- fats are much more energy-rich than carbs, proteins or ketones
Levels of ___ and ___ are markedly elevated during starvation
- glucagon and epinephrine
- lipolysis is rapid, resultign in excess Acetyl-CoA that is used for ketone synthesis
- so levels of lipids and ketones are therefore also increased in the blood
Preferred fuels in the well-fed and fasting states:
- Cardiac Muscle
- Well-Fed: FA
- Fasting: FA, ketones
Alcohol has how many kcal/gm?
Alcohol = 7 kcal/gm
The 2 main roles of liver in fuel metabolism are:
- to maintain a constant level of blood glucose under a wide range of conditions
- to synthesize ketones when excess FA are being oxidized
Preferred fuels in the well-fed and fasting states:
- Adipose Tissue
- Well-Fed: Glucose
- Fasting: FA
How does the liver respond when it detects the elevated blood glucose levels in portal blood after a meal?
- the liver extracts excess glucose from portal blood and uses it to replenish its glycogen stores
- any glucose remaining in the liver is then converted to acetyl CoA and is used for FA synthesis
- the increase in insulin after a meal simulates both glycogen synthesis and FA synthesis in the liver
- the FA are converted to TG and released into the blood as VLDLs
- in the well-fed state the liver derives most of its energy from oxidation of excess AA
Preferred fuels in the well-fed and fasting states:
- Brain
- Well-Fed: Glucose
- Fasting: Glucose, (Ketones in prolonged fast)
- after several weeks of fasting, the brain derives approx 2/3 of its energy from ketones and 1/3 from glucose
- FA can’t cross the BBB, so they’re not used
- the shift from glucose to ketones as the major fuel diminishes the amount of protein that must be degraded to support gluconeogenesis
- there is no energy-storage form of protein bc each protein has a specific function in the cell
- so the shift from using glucose to ketones during starvation spares protein, which is essential for these other functions
The increase in glucagon during fasting promotes
- glycogen degradation
- gluconeogensis
- because the liver is responsible for releasing glucose into the blood during a fast (or between meals)
What is lipoprotein lipase?
- where is it found?
- what induces it?
- lipoprotein lipase is an enzyme found in the capillary bed of adipose tissue
- it hydrolyzes TG in lipoproteins (i.e. VLDL)
- it is induced by insulin
What provides the Carbon Skeletons for glucose synthesis during a fast?
Lactate, glycerol, and AA provide Carbon skeletons for glucose synthesis during a fast
the increase in insulin after a meal simulates both ____ and ____ in the liver
the increase in insulin after a meal simulates both glycogen synthesis and FA synthesis in the liver
What is the benefit of the brain’s ability to adapt to using ketones for fuel in prolonged starvation?
- after several weeks of fasting, the brain derives approx 2/3 of its energy from ketones and 1/3 from glucose
- the shift from glucose to ketones as the major fuel diminishes the amount of protein that must be degraded to support gluconeogenesis
- there is no energy -storage form of protein bc each protein has a specific function in the cell
- so the shift from using glucose to ketones during starvation spares protein, which is essential for these other functions
in the well-fed state the liver derives most of its energy from:
in the well-fed state the liver derives most of its energy from oxidation of excess AA
What happens in Adipose tissue after a meal?
- the elevated insulin stimulates glucose uptake by adipose tissue
- insulin also stimulates FA release from VLDL and chylomicron TG (TG is aka triacylglycerol)
- lipoprotein lipase, an enzyme found in the capillary bed of adipose tissue that hydrolyzes TG in lipoproteins, is induced by insulin
- the FA that are released from lipoproteins are taken up by adipose tissue and re-esterified to TG for storage
- the glycerol phosphate required for TG synthesis comes from glucose metabolized in the adipocyte.
- insulin is also very effective in suppressing the release of FA from adipose tissue
During the fasting state, the decrease in insulin and increase in epinephrine have what effect on adipose tissue?
During the fasting state, the decrease in insulin and increase in epinephrine activate hormone-sensitive lipase in fat cells, allowing FA to be released into circulation
Describe the major fuels of resting skeletal muscle
- major fuels of resting SKM are glucose and FA
- skeletal muscle = body’s major consumer of fuel bc of its enormous bulk
- After a meal, (Insulin present): skeletal muscle takes up glucose to replenish glycogen stores and AA that are used for protein synthesis
- both excess glucose and AA can also be oxidized for energy
- in the fasting state, resting muscle uses FA derived from FFA in the blood; ketones may be used in prolonged fasting
Fast twitch muscle fibers
- have high capacity for anaerobic glycolysis
- but are quick to fatigue
- primarily involved in short-term, high intensity exercise
Short bursts of high-intensity exercise are supported by
anaerobic glycolysis drawing on stored muscle glycogen
Cardiac muscle energy sources:
- fetal energy source
- post natal energy source
- During fetal life cardiac muscle primarily uses glucose as an energy source
- but in the postnatal period there is a major switch to beta oxidation of FA
- Thus, in humans, FA serve as the major fuel source for cardiac myocytes
- can also use ketone bodies during periods of prolonged fasting
- So, cardiac myocytes energy use most closely parallels the skeletal muscle during periods of extended exercise
during moderately high, continuous exercise…
- oxidation of glucose and FA are both important
- but after 1-3 hours of continuous exercise at this level, muscle glycogen stores are depleted and the intensity of exercise declines to a rate that can be supported by:
- oxidation of FA
slow-twitch muscle fibers
- in arm and leg muscles
- are well vascularized an primarily oxidative
- used during prolonged, low-to moderate intensity exercise and resist fatigue
- slow-twitch fibers and the # of their mitochondria increase dramatically in trained endurance athletes
How does the cardiac muscle’s energy usage change in someone with cardiac hypertrophy?
in a failing heart, glucose oxidation increases and beta oxidation fails.
Although the brain represents 2% of the total body weight:
- it obtains ___ % of the Cardiac output
- uses __ % o the total O2
- and consumes ___% of the total glucose
The brain gets:
- 15% of the Cardiac output (CO)
- uses 20% of the total O2
- and consumes 25% of the total glucose
What GLUT transporter is found on the brain
GLUT 1 and GLUT 3
What changes occur in the brain during hypoglycemic conditions (less than 70 mg/dl)
- centers in the hypothalamus sense a fall in blood glucose levels
- and the release of glucagon and epinephrine is triggered
- FA cannot cross the BBB and are therefore not used at all
- btw meals, the brain relies on blood glucose supplied by either:
- hepatic glycogenolysis or gluconeogenesis
- only in prolonged fasts does the brain gain the capacity to use ketones for energy, and even its only 2/3 of fuel; 1/3 is glucose
Insulin increases glucose transport in only which tissues?
- adipose and muscle
- the major site of glucose uptake is muscle, which decreases hyperglycemia
normal blood glucose concentration
- 4-6 mM
- aka 72-110 mg/dL
- hypoglycemia: < 70
