Integration of metabolism week 4 Flashcards
Organs work together to maintain ___ and ___ homeostasis which is dictated by ___ signals.
Organs work together to maintain glucose and caloric homeostasis which is dictated by hormone signals.
This is done so there is a constant availability of fuels in the blood.
T or F: RBCs store glucose as glycogen.
False. RBCs have NO fuel reserve; continuous supply of glucose is essential.
What GLUT transporter is used by RBCs? When is glucose transported into RBCs?
What pathways is glucose used for in RBCs?
GLUT1. Regulated by free [glucose]-not by any hormones. [glucose] almost 0 intracellularly bc hexokinase phosphorylates glucose-cells with GLUT1 and GLUT3 always take up glucose.
G6P can go to glycolysis for energy production (lactate produced-goes to liver-Cori cycle). G6P can also go to the PPP for NADPH production for reduction of glutathione which is important for the protection of RBC membranes from oxidants. Additionally, there is a 2,3 BPG shunt which regulates O2 binding to Hb.
What percentage of oxygen is used by the brain?
Explain the fuel reserve of the brain.
What GLUT transporters are used in the brain? When do they transport glucose?
What is a lot of the ATP used for in the brain?
What is the PPP used for in the brain?
Brain: has very high respiratory metabolism (20% of all O2 is used in the brain). Not enough oxygen to the brain: dizziness, fainting. There is NO significant fuel reserve; continuous supply of fuels is essential.
The brain has GLUT1 and GLUT3 transporters which are regulated by blood glucose concentration.
The main fuel is glucose which is completely oxidized to CO2. A lot of the ATP is used for Na+/K+ ATPase-nerve transmission.
The PPP runs for biosynthesis of NTs and other molecules: VLCFA synthesis for myelin sheath and membranes for example
What percentage of O2 is used by skeletal muscle at rest? At maximum exertion?
What GLUT transporter is used in skeletal muscle? Under what conditions does it transport glucose?
What fuels are used to generate energy by skeletal muscle in the following conditions?:
at rest
strenuous exertion
excessive activity or fasting
Skeletal muscle: can work under aerobic and anaerobic conditions. (30% O2 is used at rest, 90% at maximum exertion). High respiratory metabolism is needed since ATP is used for contraction and relaxation.
Skeletal muscle uses GLUT4 for glucose transport into cells which is stimulated by insulin.
At rest: contains phosphocreatin and 2% glycogen as energy stores. Uses fatty acids, glucose and ketone bodies for ATP production.
Strenuous exertion: phosphocreatine (for 4 sec), glycogen (at energy burst) and glucose is used; glycolysis can produce lactate, which goes to liver (Cori cycle)
During excessive activity or fasting: protein degradation is initiated. Amino acids are converted to pyruvate or AcCoA –> TCA. Ala goes to liver (Ala cycle) for the production of glucose.
Describe the levels of energy reserves in cardiac muscle.
What GLUT transporter is present in cardiac muscle? Under what conditions does it transport glucose?
What energy sources are utilized by cardiac muscle under the following conditions?:
normal conditions
starvation
Heart muscle: highly aerobic (half of its cytosol is mitochondria). It has very low levels of energy reserves (phosphocreatin, glycogen).
Cardiac muscle uses the GLUT4 transporter which is stimulated by insulin.
Normal conditions: it uses fatty acids as energy sources, which go to TCA to produce ATP.
During starvation: fatty acids (from adipose tissue), glucose (from liver), ketone bodies (from liver) are used for energy production.
What FA does adipose tissue store? About how long does the energy stored in adipose tissue last?
Describe the glucose levels in adipose tissue. What processes is glucose metabolism used for?
What GLUT transporter is present in adipose tissue? When does it transport glucose?
What is the purpose of the PPP in adipose tissue?
What is the source of the FA in adipose tissue?
Adipose tissue: triacylglycerol storage (65% of weight can be of stored fat), which counts for app. 3 month supply of energy (average turnover app. 2 days).
Glycolysis runs for ATP production.
Adipose tissue uses the GLUT4 transporter which is stimulated by insulin.
High glucose level: glucose forms AcCoA, which is used for fatty acid synthesis (glycerol-3-P also comes from glycolysis)
Hexose monophosphate shunt runs for NADPH synthesis, which is needed for FA synthesis.
Fatty acids are also transported from liver (either synthesized there or taken up from food sources) for storage.
Starvation: fatty acids are released to blood
Explain the metabolic pathways that function in the liver.
What pathways run during fasting?
What GLUT transporter is present in the liver?
Liver: the major metabolic processing center
Glucose and amino acids enter through the portal vein.
Glycogen is synthesized from glucose; stored; later released to the blood-GLUT2 transporter which is bi-directional.
Pentose phosphate pathway runs to produce NADPH for biosynthetic reactions.
Detoxification center for the body. (Xenobiotics are modified by the CYP system; insoluble byproducts, e.g. heme, modified by glucuronic acid)
Glycolysis runs to produce energy through TCA and oxidative phosphorylation; AcCoA can be used for fatty acid synthesis (FAs are delivered to adipose tissue packaged in VLDL); and for cholesterol and bile salt synthesis.
A lot of proteins are synthesized here (all blood proteins except for immunoglobulins).
During fasting:
Glycogenolysis turns on to supply blood sugar.
Gluconeogenesis runs, from lactate (through Cori-cycle), from amino acids (Ala cycle; from muscle proteins) and from glycerol (from adipose tissue).
Urea cycle runs for the disposal of nitrogen.
Ketogenesis runs from fatty acids (from adipose tissue) and from amino acids (from muscle).
What is communication btwn tissues mediated by?
In what ways can enzymes be regulated?
Tissues function in concert with fuel metabolism. They may provide substrates to one another and/or process compounds produced by other organs.
Communication between tissues is mediated by:
- the nervous system,
-the availability of circulating substrates - variation in the levels of plasma hormones.
Regulation mechanisms for key enzymes of metabolic pathways:
1. Substrate supply, product accumulation
2. Negative and positive allosteric effectors for enzymes
3. Covalent modifications of enzymes
4. Induction-repression of enzyme synthesis
Effects of hormones (through 3 and 4)
What tissues do the following hormones act on? Explain the effects of the actions of insulin, glucagon, and epinephrine on their target tissues.
insulin
glucagon
epinephrine
glucorticoids
Insulin: liver, muscle, adipose tissue
Glucagon: liver, adipose tissue
Epinephrine: liver, muscle, adipose tissue
Glucocorticoids: liver, muscle, adipose tissue
Insulin: stimulates the storage of fuels and the synthesis of proteins
Promotes glucose entry to muscle and adipose tissue
Stimulates glycogen synthesis in both liver and muscle
Accelerates glycolysis in liver (which increases FA synthesis)
Suppresses gluconeogenesis in liver
Suppresses glycogenolysis in liver and muscle
Promotes synthesis and storage of TGs in adipose tissue
Suppresses the degradation of TGs in adipose tissue
Promotes the uptake of branched-chain AAs and protein synthesis in muscle (and in most cells)
Glucagon: increases the release of fuel molecules
Stimulates glycogen breakdown and inhibits its synthesis in liver
Stimulates gluconeogenesis and inhibits glycolysis in liver
Stimulates lipolysis in adipose tissue
Stimulates FA oxidation in liver and the production of ketone bodies
Inhibits FA synthesis
Epinephrine: Effect is greater on muscle than on liver
Similar to glucagon
Increases the release of glucose by liver and inhibits the utilization of glucose by muscle (glucose uptake)
Stimulates glycogenolysis and lipolysis
(Also increases blood pressure and the output of the heart)
see figures on pgs 268 and 271 of course notes for summary
What molecules stimulate insulin secretion?
What molecules stimulate glucagon secretion?
What effects do epinephrine and norepinephrine have on insulin and glucagon secretion?
Under what conditions are E and NE secreted? What organs/systems play a role in this?
Circulating substrate levels in blood- involvement of pancreas
High glucose and amino acid levels from food stimulate insulin secretion.
Low glucose (and partially high amino acid) levels stimulate glucagon secretion.
Stress, trauma or severe exercise (also cold and low blood glucose) –with the involvement of hypothalamus, pituitary, adrenal medulla and the autonomic nervous system (see figure and Physiology)
Epinephrine, produced by the adrenal medulla, and norepinephrine, stimulate the release of glucagon. Thus, during stressful situations, elevated epinephrine levels can override the effect of circulating substrates.
Explain the following types of hypoglycemia. State when/why they occur and how they can be treated (if applicable):
insulin-induced hypoglycemia
postpraindial hypoglycemia
fasting hypoglycemia
alchohol induced hypoglycemia
Remember that hypoglycemia is NEVER normal!
- Insulin-induced hypoglycemia – occurs in diabetic patients receiving insulin treatment. Can be treated by oral administration of carbohydrates or injection of glucagon.
- Postprandial hypoglycemia – transient hypoglycemia induced by exaggerated insulin release after meal. Treatment is consumption of frequent small rather than large meals.
- Fasting hypoglycemia – reduced gluconeogenesis by liver, especially in cases of hepatocellular damage or adrenal insufficiency, or overproduction of insulin resulting from pancreatic beta-cell tumor (remember special case is G6-phosphatase deficiency when neither glycogen nor gluconeogenesis can supply glucose from liver-von Gierkes dz).
- Alcohol induced hypoglycemia – overproduction of NADH by alcohol dehydrogenase halts hepatic gluconeogenesis. Especially serious when hepatic glycogen stores are depleted (after exercise or in fasting). It also results in lactic acidosis.
About how long is the well-fed state?
After a meal, what are the relative levels (high, low) of insulin, glucagon, epinephrine, and glucocorticoids?
What processes are running during this time? What processes are not running?
What processes run during this time in the liver, muscle, and adipose tissue specifically?
What is the main energy source during this time period?
Liver
- glycogenesis
- glycolysis
- lipogenesis (VLDL
- HMPS
Muscle
- glycogenesis
- glycolysis
Adipose
- glycolysis (glycerol-3-P)
- lipogenesis (and storage from VLDLs and chylomicrons)
- HMPS
Main energy source: glucose from food
processes occurring during well fed state
About how long is the between meals state?
During this time period? what are the relative levels (high, low) of insulin, glucagon, and epinephrine?
What processes are running during this time? What processes are not running?
What processes run during this time in the liver, muscle, and adipose tissue specifically?
What is the main energy source during the in btwn meals state?
Liver
- glycogenolysis
- gluconeogenesis
- Cori and Alanine cycles
Muscle
- glycogenolysis
- glycolysis
- Cori and Alanine cycles
Adipose
- no significant processes
Main energy source: glucose from glycogen and gluconeogenesis (blood glucose)
processes occurring btwn meals
About how long is the early fasting state?
What processes are running during this time? What processes are not running?
What processes run during this time in the liver, muscle, and adipose tissue specifically?
What is the main energy source during the early fasting state? Which tissues utilize which sources of energy?
attached is slide 25 of notes
About how long is the intermediate fasting state?
What processes are running during this time? What processes are not running?
What processes run during this time in the liver, muscle, and adipose tissue specifically?
What is the main energy source during the intermediate fasting state? Which tissues utilize which sources of energy?
Liver
- gluconeogenesis
- FA B-oxidation
- Urea cycle
- Cori and Alanine cycles
- Ketogenesis
Muscle
- Cori and Alanine cycles
- proteolysis
- FA oxidation
- ketone body utilization
Adipose
- lipolysis
Main energy source:
storage fat – liver, muscle, kidney, heart
ketone bodies – muscle, heart, kidney, brain
glucose – brain (decreased level), RBC, WBC, adrenal medulla, retina
processes occurring during the intermediate fasting state
Note: gut enzymes begin to stop working bc not eating. from aa breakdown, glutamine goes to the gut to provide energy for enterocytes.
About how long is the starvation (advanced fasting) state?
What processes are running during this time? What processes are not running?
What processes run during this time in the liver, muscle, and adipose tissue specifically?
What is the main energy source during the starvation state? Which tissues utilize which sources of energy?
During the early re-fed state after fasting, what is the source of fuel supply?
Explain fat and glucose metabolism during this stage.
Fuel is supplied by food.
Fat is metabolized normally, but normal glucose metabolism is re-established slowly.–>(Because time is needed to recover enzymes for glycolysis and fatty acid synthesis after long-time suppression)
Liver stays in gluconeogenic mode for a few hours.
After few hours: liver glycolysis starts. Glycogen is synthesized directly from glucose supplied by food.
glucose (food)–> lactate (other tissues)–> glucose production (gluconeogenesis in liver) –> glycogen (in liver). aa from food also go to the liver for glycogen production.
switch in liver metabolism
see reverse
List the main fuel molecules and sources of fuels that maintain glucose homeostasis during the following phases:
I. well fed
II. between meals
III. starvation (<20 hours)
IV. starvation (<24 days)
V. prolonged starvation
