31 - Integration of Metabolism Flashcards
PFK activity is stimulated/inhibited by?
Stimulated AMP or ADP
Inhibited ATP and citrate
PFK is also regulated by F-2,6-bisP, which is governed by epinephrine and glucagon levels through cAMP.
How do the following tissues respond to cAMP?
Liver
Heart
Skeletal muscle
F-2,6-bisP allosterically stimulates PFK (and therefore glucose breakdown/glycolysis)
Liver
- Decrease in F-2,6-bisP
Heart
- Increase in F-2,6-bisP
Skeletal muscle
- F-2,6-bisP does not respond to cAMP
What does gluconeogenesis need to bypass irreversible steps of glycolysis?
F-1,6-bisPase and G-6-Pase
Reciprocal regulation of gluconeogenesis and glycolysis determines rate and direction.
How is glycogen synthesized and mobilized?
- Glycogen is stored mostly in liver and muscle
- Mobilization to G-6-P is catalysed by glycogen phosphorylase and the
reverse reaction by glycogen synthase - Reciprocal regulation by phosphorylation/dephosphorylation cycles of the phosphorylase and synthase that are stimulated by insulin, glucagon
and epinephrine through cAMP - Glucagon:insulin ratio determines whether glycogen is synthesized or
degraded
How are fatty acids synthesized and oxidized (mobilized)?
Synthesis is regulated by ___?
What inhibits synthesis?
- Level of beta-oxidation is determined by fatty acid concentration
- Fatty acids are mobilized by tissue TG lipases, usually stimulated by
epinephrine/glucagon and phosphorylation status via cAMP - Synthesis is regulated by ACC and level of citrate, insulin-dependent
dephosphorylation - Inhibition of synthesis by palmitoyl-CoA
- Glucagon:insulin ratio determines the direction
What happens when the citric acid cycle uses acetyl-CoA without pyruvate?
Consumption of cycle intermediates
Enzymes of cycle are regulated by substrate availability, NADH and ATP levels.
What happens when the citric acid cycle uses acetyl-CoA without pyruvate?
Consumption of cycle intermediates
Enzymes of cycle are regulated by substrate availability, NADH and ATP levels.
What does amino acid synthesis and degradation do for TCA cycle, glycolysis and gluconeogenesis?
Provides aKG for citric acid cycle, glycolysis and gluconeogenesis.
Some common amino acids are only able to produce ketones, not glucose.
Why does the brain consume so much oxygen?
To maintain membrane potential via Na/K ATPase
GLucose is the normal fuel, but ketone bodies are used if prolonged fasting occurs.
No storage of glycogen.
TG hydrolyzes stored TG in response to?
- Glucagon
- Epinephrine
Inhibited by insulin
What are the four possible fates of G-6-P in the liver?
Depends on metabolic requirements.
(i) converted to glucose when blood glucose levels are low
(ii) converted to glycogen when blood glucose is adequate
(iii) oxidized to acetyl-CoA (used for energy or lipid biosynthesis) (iv) converted to NADPH for biosynthetic processes
What are the three possible fates of fatty acids in the liver?
(i) can be converted to ketones for use as metabolic fuel
(ii) used to synthesize TG when demand for energy is low
(transported to and stored in adipose tissue)
(iii) compartmentalization of fatty acids prevents futile cycling
(malonyl CoA prevents uptake of FA into mitochondria)
What are the main sources of energy for the liver?
Fatty acids and amino acids
NOT glucose or ketones
What are the main sources of energy for the liver?
Fatty acids and amino acids
NOT glucose or ketones
How can muscle protein be broken down for energy?
Amino acids released from muscle proteins can be converted to pyruvate then alanine and transported back to the liver for gluconeogenesis in the alanine-glucose cycle.
How can muscle protein be broken down for energy?
Amino acids released from muscle proteins can be converted to pyruvate then alanine and transported back to the liver for gluconeogenesis in the alanine-glucose cycle.
Muscle responds to ___ to regulate glycogen synthesis and breakdown
epinephrine but not glucagon (no receptors)
What does increase in cAMP in heart tissue do?
Stimulates glycogen breakdown and glycolysis for glucose consumption. This is in contrast to the liver, in which glucagon acts via cAMP to regulate blood glucose levels.
What happens if glycolysis runs out of oxygen supply?
Glycolysis will be anaerobic and generate lactate.
The cori cycle converts lactate to glucose in the liver.
What type of fuel do heart muscles rely on?
Heart muscle relies entirely on aerobic metabolism, and uses fatty acids primarily but can use any fuel source if required
Absence of the hypothalamus will lead to obesity how?
The lipostate will be gone.
Leptin produced by adipocytes suppresses appetite by acting on hypothalamic receptors.
Leptin deficiency can cause obesity in humans, but is rare. Rather target tissues have developed leptin resistance.
What does leptin do?
Stimulates fatty acid oxidation and inhibits the accumulation of TG in non-adipose tissues by inactivating ACC.
This reduces malonyl-CoA and increases FA transport into mitochondria.
Insulin also seems to be a component of the lipostat mechanism as it also acts in the hypothalamus to decrease food intake.
What is ghrelin?
peptide secreted by empty stomach to stimulate appetite.
Injection leads to increase in adipose tissue in rodents. In humans, plasma levels are low in the fed state and increase in the fasted state.
What is adaptive thermogenesis?
Occurs in response to cold temperature and involves the increased expression of “uncoupling proteins” which discharges the H+ gradient in the mitochondrion such that energy if dissipated as heat
Especially important in brown adipose tissue
What is adaptive thermogenesis?
Occurs in response to cold temperature and involves the increased expression of “uncoupling proteins” which discharges the H+ gradient in the mitochondrion such that energy if dissipated as heat
Especially important in brown adipose tissue
Why can fatty acids not be used to synthesize glucose?
Because the pyruvate or oxaloacetate required for gluconeogenesis cannot be synthesized from acetyl-CoA
Oxaloacetate IS made from acetyl-CoA, but is consumed as fast as it is synthesized in the TCA cycle
What happens to glucose synthesis during starvation?
What is survival dependent on?
How is starvation similar to diabetes mellitus?
During starvation, glucose is synthesized in the liver from glycerol (from TG breakdown) and a-ketoacids (from amino acids of muscle proteins).
After several days, ability to metabolize acetyl-CoA is almost zero
Instead the acetyl-CoA is converted to ketones muscle breakdown will stop
Survival during prolonged starvation is dependent on the size of the fat storage pool
diabetes mellitus = starvation due to inability of cells to access available glucose
