Metabolism I & II: Overview of Metab. & Glycolysis

Question 1

What is glycogenolysis? What promotes it?

Answer 1

the biochemical breakdown of glycogen to glucose; promoted by glucagon and epinephrine

Question 2

What is glycolysis? What promotes it?

Answer 2

the breakdown of glucose by enzymes to extract energy for cellular metabolism; promoted by insulin

Question 3

What is gluconeogenesis? What promotes it?

Answer 3

the generation of glucose from certain non-carbohydrate carbon substrates; promoted by glucagon and epinephrin

Question 4

What is glycogenesis? What promotes it?

Answer 4

the formation of glycogen from sugar (glucose molecules added to chains of glycogen for storage); promoted by insulin

Question 5

What is the reverse process of glycolysis?

Answer 5

gluconeogenesis

Question 6

What are the 3 ways to regulate enzyme activity?

Answer 6

1) Allosteric regulation (pos./neg.)
2) Covalent modification (phosphor./dephosphor.)
3) Induction/repression of enzyme synthesis by hormones (insulin/glucagon)

Question 7

ATP is always in the presence of which cofactor?

Answer 7

Mg2+ (a divalent metal cation)

Question 8

What are the 4 fates of Ac-CoA?

Answer 8

1. Primary fate: oxidation of acetyl groups in the CAC for energy production (this is a combustion rxn)
2. Formation of fatty acids (lipogenesis) that can then be esterified to form TAGs
3. Ketogenesis
4. Cholesterologenesis (cholesterol can then be synthesized into steroids)

Question 9

Where does the conversion of pyruvate to Ac-CoA take place?

Answer 9

mitochondrial matrix

Question 10

True or false: The consumption of calories from all components can lead to the formation of fat.

Answer 10

True- all components of metabolism can give rise to the synthesis/storage of fat by first converting into acetyl CoA.

Question 11

What is the fuel preference of the liver?

Answer 11

fatty acids, glucose, amino acids

Question 12

What is the fuel preference of adipose tissue?

Answer 12

fatty acids

Question 13

What is the fuel preference of skeletal muscle?

Answer 13

• at rest: fatty acids

- exertion: glucose

Question 14

What is the fuel preference of heart muscle?

Answer 14

fatty acids

Question 15

What is the fuel preference of the brain?

Answer 15

• fed state: glucose

- starvation: ketone bodies / glucose

Question 16

What are the major dietary carbohydrates?

Answer 16

amylose, sucrose, lactose, fructose, glucose

Question 17

What is the typical food source of the major dietary carbohydrates?

Answer 17

• amylose: potatoes, rice, corn, bread
• sucrose: table sugar, desserts
• lactose: milk, milk products
• fructose: fruit, honey
• glucose: fruit, honey, grapes

Question 18

What are the consequences of a lactose intolerant person consuming milk?

Answer 18

• dietary lactose is not sufficiently hydrolyzed or absorbed, so it remains in the intestine and causes osmosis of water into the intestine; intestinal bacteria metabolize the lactose to produce lactic acid and a mixture of hydrogen, CO2, and methane gas
• result: bloating, flatulence, diarrhea

Question 19

Compare the pathways of carbohydrate metabolism that are active in red blood cells, brain,
skeletal muscle, heart, adipocytes, and hepatocytes.
???

Answer 19

• RBCs: lack mitochondria, so rely entirely on glycolysis
• brain: absolute requirement for glucose (glycolysis); very small reserve of glycogen; products of glycolysis feed into CAC to produce energy
• muscle and heart: major stores of glycogen, which can be converted to products that feed into CAC (muscle cells can also reduce pyruvate to lactate)
• adipocytes: excess glucose converted to fat via lipogenesis
• hepatocytes: glycolysis, gluconeogenesis, glycogen synthesis, PP pathway

Question 20

Identify the glucose/monosaccharide transporters (GLUTs) that are responsible for Na+
dependent glucose transport.

Answer 20

SGLT1, SGLT2

Question 21

Which are the insulin-dependent glucose transporters?

Answer 21

we only talked about one of them, GLUT4 (in muscle, heart, and adipocytes)

Question 22

Which are the insulin-independent glucose transporters? Of those, which is the low affinity but high capacity transporter in the liver?

Answer 22

GLUT1, GLUT2, GLUT3
(GLUT2 is the low affinity, high capacity transporter that transports glucose out of the intestine, through the bloodstream, and into the liver)

Question 23

Which 3 glycolytic reactions are irreversible under physiological conditions? List the enzymes that catalyze each.

Answer 23

1) glucose –> glucose-6-phosphate (hexokinase/glucokinase)
2) fructose-6-phosphate –> fructose-1,6-bisphosphate (PFK-1)
3) phosphoenolpyruvate –> pyruvate (pyruvate kinase)

Question 24

Acute hypoglycemia causes neurological problems, coma, and death. Therefore, fating blood glucose levels must be maintained above______.

Answer 24

60 mg/100 mL

Question 25

Compare hexokinase vs. glucokinase.

Answer 25

Hexokinase: -in all cell types -constitutive enzyme (non-inducible, constant amount) -low Km for glucose Glucokinase: -in liver and pancreas -translocation b/t nucleus (inactive) and cytosol (active) -inducible enzyme (synthesis increased by insulin) -high Km for glucose (not saturated at physiological [glucose])

Question 26

What are the allosteric activators and inhibitors of hexokinase?

Answer 26

- activators: none, as it is a constitutive enzyme | - inhibitors: its product, G6P

Question 27

What are the allosteric activators and inhibitors of glucokinase?

Answer 27

- activators: glucose (promotes translocation into cytosol) and fructose (inhibits translocation into nucleus) - inhibitors: F6P (promotes translocation into nucleus)

Question 28

What are the allosteric activators and inhibitors of PFK-1?

Answer 28

- activators: AMP, ADP, F-2,6-BP | - inhibitors: ATP, citrate

Question 29

What are the allosteric activators and inhibitors of pyruvate kinase?

Answer 29

- activators: PEP, ADP, F-1,6-BP | - inhibitors: ATP, alanine

Question 30

Explain the differing effect of epinephrine on hepatic glycolysis vs. glycolysis in the heart and skeletal muscle.

Answer 30

epi inhibits hepatic glycolysis but stimulates heart and skeletal muscle glycolysis

Question 31

Glucagon and epinephrine cause the covalent modification (phosphorylation) of 2 key enzymes:

Answer 31

- inhibit PFK-2, leading to decreased F-2,6-BP, thus decreasing PFK-1 activity - inhibit pyruvate kinase

Question 32

Glucagon and epinephrine repress the synthesis of 3 glycolytic enzymes in the liver:

Answer 32

glucokinase, PFK-1, pyruvate kinase

Question 33

What is the pancreatic hormone that leads to inhibition of hepatic glycolysis?

Answer 33

glucagon, by repressing the synthesis of 3 glycolytic enzymes in the liver (glucokinase, PFK-1, and pyruvate kinase)

Question 34

Does insulin activate or inhibit glycolysis?

Answer 34

it activates glycolysis in order to utilize glucose and therefore lower its levels in the blood

Question 35

How does epinephrine inhibit hepatic glycolysis but activate cardiac glycolysis?

Answer 35

- inhibits hepatic glycolysis by inhibiting PFK-2, which decreases F-2,6,-BP, which decreases PFK-1 activity - activates cardiac glycolysis by inhibiting fructose-2,6-bisphosphatase activity (inhibition of phosphatase activity increases the amt. of F-2,6-BP, thereby activating PFK-2)

Question 36

Compare the conditions in which the favored end product of glycolysis is lactate with the conditions that promote formation of pyruvate and Ac-CoA.

Answer 36

anaerobic metabolism favors conversion of pyruvate to lactate (Nad+ replenished through reduction rnx leading to lactate or ethanol), while aerobic metabolism favors formation of pyruvate and Ac-CoA that feed into the CAC for energy.

Question 37

Predict the effects of ischemia, caused by a brain tumor, on lactate formation in the brain.

Answer 37

brain tissue in area of ischemia would switch over to anaerobic metabolism, causing a buildup of lactic acid in the brain

Question 38

What are the 3 ways to regenerate NAD+?

Answer 38

1) lactate dehydrogenase (cytosolic rxn) 2) malate-aspartate shuttle (cytosol and MT) 3) glycerol-phosphate shuttle (cytosol and MT)

Question 39

What are the allosteric inhibitors of PDH?

Answer 39

NADH and Ac-CoA (the end products of PDH rxn)

Question 40

Predict the effect of covalent modification/phosphorylation on PDH activity.

Answer 40

phosphorylation of PDH by a kinase activated by PDH end products inhibits the enzyme (PDH is inactive in a phosphorylated state and active in a dephosphorylated state)

Question 41

How is PDH affected by glucagon and epinephrine?

Answer 41

it is NOT regulated by glucagon and epinephrine

Question 42

Identify the 3 glycolytic rxns that are irreversible under physiological conditions, and list the enzymes that catalyze each.

Answer 42

1. glucose --> glucose-6-phosphate (hexokinase/glucokinase) 2. fructose-6-phosphate --> fructose-1,6-bisphosphate (PFK-1) 3. phosphoenolpyruvate --> pyruvate (pyruvate kinase)