Exam 3 December 9 Lecture

Question 1

What is glucagon?

Answer 1

1. a peptide hormone produced by alpha cells of the pancreas
2. a first messenger (hormone) so it can’t get into cells but it stimulates the production of a second messenger
3. released upon the drop in blood glucose levels → happens at night
4. raises the concentration of glucose and fat in the bloodstream → it promotes the hydrolysis of triacylglycerol and mobilizes fat as an energy source (fatty acid oxidation)
5. binds to a GPCR (glucagon receptor) which activates Gs (adenylate cyclase stimulator)

Question 2

What is the difference between glucagon and insulin?

Answer 2

they are complete opposites of one another and are produced by the cells in the pancreas → beta cells produce insulin and alpha cells produce glucagon

Question 3

What is cyclic AMP?

Answer 3

1. a second messenger so it can enter cells
2. produced from ATP by adenylate cyclase
3. hydrolyzed by phosphodiesterase
4. activates cAMP-dependent protein kinase (protein kinase A)
5. protein kinase A phosphorylates many proteins and can turn off certain pathways

Question 4

Is protein kinase A usually active or inactive?

Answer 4

normally inactive and is a tetramer → has 2 regulatory subunits and 2 inactive catalytic subunits

Question 5

What is 6-phosphofructto-2-kinase/fructose 2,6-bisphosphatase?

Answer 5

1. bifunctional enzyme with both kinase and phosphatase activity (has both domains) → like a janus enzyme (2 faced)
2. controls the concentration of fructose 2,6-bisphosphate, an allosteric effector, which activates 6-phosphofructo-1-kinase and suppresses fructose 1,6-bisphosphatase
3. fructose 2,6-bisphosphate increases glycolysis and suppresses gluconeogenesis

Question 6

What is the conversion to fructose 6-phosphate to fructose 1,6-bisphosphate an example of?

Answer 6

a futile cycle → if both cycles/domains are on, it will waste ATP so only 1 is on and the other is off in which switching is dictated by phosphorylation (ALSO AN IRREVERSIBLE STEP)

Question 7

If there is more of an allosteric regulator, what happens?

Answer 7

will increase glycolysis and make it go faster

Question 8

What are the 3 regulated enzymes of glycolysis?

Answer 8

1. glucokinase
2. 6-fructo-1-kinase
3. pyruvate kinase

Question 9

What happens when the 3 regulated enzymes of glycolysis is ON/OFF?

Answer 9

ON → glycolysis is ON and gluconeogenesis is OFF

OFF → glycolysis is OFF and gluconeogenesis is ON

Question 10

What is the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in the liver?

Answer 10

1. phosphorylation by protein kinase A switches the enzyme from a kinase to a phosphatase which decreases fructose 2,6-P2 level → glycolysis slows down and gluconeogenesis revs up
2. epinephrine also increases cAMP which shows the same effects in the liver as glucagon
3. upon the release of glucagon or epinephrine, the liver releases glucose to the bloodstream

Question 11

What happens in the liver?

Answer 11

glucagon OR epinephrine → cAMP levels increase → protein kinase A → fructose 2,6-bisphosphatase → fructose 2,6-P2 levels decrease → glycolysis slows down and gluconeogenesis increases

Question 12

What is the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in the heart?

Answer 12

1. the heart has an isoenzyme different from the liver enzyme
2. the heart can use glucose as an energy source
3. phosphorylation by protein kinase A switches the isoenzyme from a phosphatase to a kinase (which is switched in the liver since protein kinase A phosphorylates the enzyme and it becomes a phosphatase)
4. epinephrine increases fructose 2,6-bisphosphate which stimulates glycolysis → enhanced so more ATP is generated

Question 13

What does epinephrine do?

Answer 13

stimulates the heart and is a fight/flight hormone so that it pumps blood fast so that the heart beat increases and blood sugar levels increase as well

Question 14

What happens in the heart?

Answer 14

epinephrine → cAMP levels increase → protein kinase A → 6-phosphofructo-2-kinase → increased levels of fructose 2,6-P2 → glycolysis increases/is stimulated

Question 15

How is pyruvate kinase inactivated in the liver?

Answer 15

1. protein kinase A inactivates pyruvate kinase by phosphorylation → glycolysis is turned OFF
2. phosphoenolpyruvate (PEP) is not converted to pyruvate but used for gluconeogenesis
   (pyruvate kinase is the third irreversible step in glycolysis)

Question 16

How are gluconeogenic enzymes induced in the liver?

Answer 16

1. induction of enzymes results in long term effects on metabolism: glucagon → cAMP → protein kinase A
2. protein kinase A phosphorylates cAMP-response element binding protein (CREB) which is a transcription factor
3. activated CREB binds to cAMP-response element (CRE) which is a cis acting element within the regulatory region of genes responsive to cAMP
4. genes for PEP carboxykinase ( key enzyme for gluconeogenesis in which the first step catalyzed by it and is irreversible), fructose 1,6-bisphosphatase, glucose 6-phosphatase are responsive to cAMP
5. glucagon also represses the expression of glucokinase, 6-phosphofructo-1-kinase, and pyruvate kinase → gluconeogenesis is faster

Question 17

What is glucagon’s effect on gene expression?

Answer 17

glucagon regulates gene expression → is slow and takes time so the effect is delayed and takes awhile

Question 18

How is glycogen breakdown stimulated in the liver?

Answer 18

1. glucagon and epinephrine stimulate glycogen breakdown in the liver
2. by phosphorylation, protein kinase A activates glycogen phosphorylase and inactivates glycogen synthase → activated glycogen phosphorylase breaks down glycogen to glucose-1-phosphate (can be converted to glucose) → 1 glucose is released at a time
3. because protein kinase a also suppresses glycolysis in the liver, glucose is readily released to the bloodstream (by the liver)

Question 19

What happens if protein kinase A does not inactivate glycogen synthase?

Answer 19

the futile cycle will occur

Question 20

What is insulin?

Answer 20

1. a peptide hormone produced by beta cells in the pancreas
2. released upon the rise in blood glucose levels
3. reduces the concentration of glucose in the bloodstream
4. binds to a receptor tyrosine kinase (insulin receptor) → phosphorylates lots of enzymes/proteins → increase transport of glucose/glucose transporters
5. promotes glucose uptake, glycogen synthesis, glycolysis, and fatty acid synthesis

Question 21

What is the effect of insulin on promoting fatty acid synthesis?

Answer 21

can cause weight gain since insulin can make you fat → need a low carb diet

Question 22

What is the mechanism of insulin?

Answer 22

1. opposes the actions of glucagon and epinephrine
2. activates cAMP phospdieterase which lowers cAMP levels
3. activates phosphoprotein phosphatase which reverses the actions of protein kinase A
4. dephosphorylation converts fructose 2,6-bisphosphatase to 6-phosphofructo-2-kinase
5. dephosphorylation activates pyruvate kinase → glycolysis is faster

Question 23

What does insulin do?

Answer 23

insulin → phosphoprotein phosphatase → 6-phosphofructo-2-kinase → fructose 2,6-P2 increases → glycolysis increases

Question 24

How does glucagon promote fatty acid oxidation?

Answer 24

1. increases in triacylglycerol breakdown by phosphorylation of hormone-sensitive lipase
2. suppresses acetyl CoA carboxylase by phosphorylation

Question 25

How does insulin promote fatty acid synthesis (have plenty of energy and need to synthesize fat for the future)?

Answer 25

1. increases the levels of key enzymes including fatty acid synthase and acetyl CoA carboxylase 2. activates acetyl CoA carboxylase by dephosphorylating the enzyme 3. activates pentose phosphate pathways by increasing the key enzymes

Question 26

What does acetyl CoA carboxylase do?

Answer 26

converts acetyl CoA to malonyl CoA (building block for fatty acid synthesis and is the commitment step of fatty acid synthesis) → how fast we generate malonyl CoA determines how fast we synthesize our fat

Question 27

What does protein kinase A do?

Answer 27

is active when we're hungry so we don't need to make fat (need to break down fat) → we don't have to eat for a month and we can be fine

Question 28

What is the Warburg effect?

Answer 28

1. discovered by Otto Warburg in the 1950s 2. when oxygen is plentiful, cancer cells convert glucose to lactate → generate little ATP 3. rapidly growing cancer cells use glucose 200 times more than normal cells → PET scan can detect cancer by radiolabeled isotype glucose since cancer cells will accumulate glucose so the cancer cells will shine like stars on the PET scan

Question 29

What is the relationship between cancer cells and glucose?

Answer 29

cancer cells use glucose insufficiently → Warburg believed that inefficiency of glucose caused cancer → WRONG

Question 30

Why is anaerobic glycolysis not efficient and what is its effect?

Answer 30

with no oxygen, little ATP is produced which is why lactic acid hurts since there is not enough oxygen

Question 31

What is the basis of cells utilizing glucose and the effect oxygen has on it?

Answer 31

cells utilize glucose to convert pyruvate which goes to the mitochondria to be converted to acetyl CoA to go to the TCA cycle to eventually become CO2 → 1 glucose can generate 36 ATP (efficient) → but to use acetyl CoA we need O2 so without it, we can't do it → how much ATP we generate in our muscle is limited to how fast we can supply oxygen → breathe heavily to supply oxygen when winded → when O2 is not present, glycolysis stops at lactate since we can't run the TCA cycle

Question 32

What are the molecules in the gluco world useful for?

Answer 32

is more useful for growth → can be used to make ribose, amino acids, and other building blocks

Question 33

What are the molecules in the keto world useful for?

Answer 33

can make fatty acids or ketone bodies once the molecules enter the keto world → basically useless

Question 34

Why is it that cancer cells keep the carbons in the gluco world?

Answer 34

cancer cells need to grow quickly and need lots of building blocks → they slow down the breach so they keep all carbons in the gluco world and minimize passage to the keto world → how cancer cells ensure their growth