T19 - Integrated Metabolism

Question 1

What are the three principles of metabolism?

Answer 1

brain needs glucose

early humans never know when their next meal would come

human body avoids futile cycling

Question 2

What is the hierarchy of energy?

Answer 2

glucose > glycogen > TGs > protein

Question 3

What cellular processes take place in the cytoplasm? (3)

Answer 3

glycolysis

PPP

fatty acid synthesis

Question 4

What cellular processes take place in the inner mitochondrial membrane?

Answer 4

oxidative phosphorylation

Question 5

What cellular processes take place in the mitochondrial matrix? (3)

Answer 5

TCA cycle

beta oxidation

ketone body synthesis

Question 6

What is the only organ/tissue that is capable of carrying out all the reactions of the major metabolic pathways?

Answer 6

liver

Question 7

What are the key junction points of all the major metabolic pathways? (3)

Answer 7

glucose-6-phosphate

pyruvate

acetyl-CoA

Question 8

What happens to glucose as soon as it’s transported into the cell?

Answer 8

converted to G6P, where it can then:

(1) undergo catabolism to pyruvate
(2) be stored as glycogen
(3) be shunted into PPP

Question 9

Describe the role of pyruvate as a junction point.

Answer 9

pyruvate is generated from G6P from glycolysis, and it can:

(1) form OAA for gluconeogensis or to replenish TCA intermediates
(2) be reduced into acetyl-CoA
(3) be converted to lactate in anaerobic conditions

Question 10

Describe the role of acetyl-CoA as a junction point.

Answer 10

formed by oxidative decarboxylation of pyruvate or beta oxidation of fatty acids, it can:

(1) be completely oxidized by TCA
(2) converted to HMG-CoA for ketone or cholesterol synthesis
(3) be sent to the cytosol for fatty acid synthesis

Question 11

(T/F) The brain has no capacity to store fuels.

Answer 11

True. This is why maintaining glucose levels is so necessary for the brain.

Question 12

The average brain consumes how much glucose per day?

Answer 12

150 g per day, which is 60% of our glucose usage

Question 13

What molecule transports glucose into the brain?

Answer 13

GLUT3

Question 14

Describe the saturation of GLUT3 at physiological conditions.

Answer 14

GLUT3 has Km for glucose of 1.6 mM, but blood [glucose] is 5 mM, so the transporter is saturated under normal conditions → continuous, steady supply of glucose for brain

Question 15

What is the lower limit of blood [glucose] for normal brain activity?

Answer 15

2.2 mM — if blood [glucose] drops below this, then brain is in trouble → coma → brain death

Question 16

Muscle cells lack what two key enzymes found in other major metabolic pathways? What are the consequences of these absences?

Answer 16

lack fatty acid synthase → can’t synthesize fatty acids for export

lack glucose-6-phosphatase → can’t release glucose from glycogen degradation

Question 17

Muscles account for what percentage of total oxygen consumption in the resting state? How does this percentage change in response to strenuous exercise?

Answer 17

50% of oxygen in resting state → becomes 90% during strenuous exercise

Question 18

What is the function of phosphocreatine in muscle cells?

Answer 18

used to rapidly regenerate ATP from ADP using phosphocreatine kinase

Question 19

Describe how the state of phosphocreatine changes during exercise.

Answer 19

during exercise: phosphocreatine → creatine

during covery: creatine → phosphocreatine

Question 20

What is the cause of muscle fatigue?

Answer 20

decrease in pH (can fall to 6.4) caused by production of lactate

Question 21

What is the effect of pH on PFK activity?

Answer 21

low pH activity diminishes PFK activity

Question 23

During excessive activity or fasting, muscle tissue is degraded into what molecules? What are these molecules used for? (5)

Answer 23

muscle tissue degraded into amino acids → [alanine transaminase] → alanine → absorbed by liver → deaminated to form pyruvate → glucose via gluconeogenesis

Question 24

In the resting state, what fraction of the resting muscle’s needs are met by fatty acid catabolism?

Answer 24

85%

Question 25

(T/F) The heart always functions aerobically.

Answer 25

True

Question 26

What are the possible fuels for the heart muscle?

Answer 26

fatty acids (fuel of choice)

ketone bodies (preferred over glucose)

lactate

Question 27

What critical role does the kidney play in starvation conditions?

Answer 27

can produce up to half of the blood’s glucose via gluconeogenesis by using amino acid sources

Question 28

The liver lacks what ketone body-related enzyme?

Answer 28

liver lacks succinyl-CoA transferase, meaning that while it can produce ketone bodies, it can’t use them, so ketone bodies are released into blood

Question 29

Glucose-6-phosphate is only found in which tissues?

Answer 29

liver

kidney

Question 30

Amino acids are catabolized in what tissue?

Answer 30

liver

Question 31

Enzymes associated with the urea cycle are only found in what tissue?

Answer 31

liver

kidney

Question 32

What component of a triacylglycerol can actually be used as a glucose source?

Answer 32

glycerol moiety

Question 33

Describe the metabolic changes associated with the transition from the fasting state to the starvation state. (4)

Answer 33

muscles stop relying on ketone bodies for fuel and instead use fatty acids stored in adipose tissue

ketone bodies used by brain instead

reduced urea production because of reduced AA catabolism

small amount of glucose produced by liver to supply RBCs, but everything else fueled by fatty acids