T19 - Integrated Metabolism Flashcards
What are the three principles of metabolism?
brain needs glucose
early humans never know when their next meal would come
human body avoids futile cycling
What is the hierarchy of energy?
glucose > glycogen > TGs > protein
What cellular processes take place in the cytoplasm? (3)
glycolysis
PPP
fatty acid synthesis
What cellular processes take place in the inner mitochondrial membrane?
oxidative phosphorylation
What cellular processes take place in the mitochondrial matrix? (3)
TCA cycle
beta oxidation
ketone body synthesis
What is the only organ/tissue that is capable of carrying out all the reactions of the major metabolic pathways?
liver
What are the key junction points of all the major metabolic pathways? (3)
glucose-6-phosphate
pyruvate
acetyl-CoA
What happens to glucose as soon as it’s transported into the cell?
converted to G6P, where it can then:
(1) undergo catabolism to pyruvate
(2) be stored as glycogen
(3) be shunted into PPP
Describe the role of pyruvate as a junction point.
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
Describe the role of acetyl-CoA as a junction point.
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
(T/F) The brain has no capacity to store fuels.
True. This is why maintaining glucose levels is so necessary for the brain.
The average brain consumes how much glucose per day?
150 g per day, which is 60% of our glucose usage
What molecule transports glucose into the brain?
GLUT3
Describe the saturation of GLUT3 at physiological conditions.
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
What is the lower limit of blood [glucose] for normal brain activity?
2.2 mM — if blood [glucose] drops below this, then brain is in trouble → coma → brain death
Muscle cells lack what two key enzymes found in other major metabolic pathways? What are the consequences of these absences?
lack fatty acid synthase → can’t synthesize fatty acids for export
lack glucose-6-phosphatase → can’t release glucose from glycogen degradation
Muscles account for what percentage of total oxygen consumption in the resting state? How does this percentage change in response to strenuous exercise?
50% of oxygen in resting state → becomes 90% during strenuous exercise
What is the function of phosphocreatine in muscle cells?
used to rapidly regenerate ATP from ADP using phosphocreatine kinase
Describe how the state of phosphocreatine changes during exercise.
during exercise: phosphocreatine → creatine
during covery: creatine → phosphocreatine
What is the cause of muscle fatigue?
decrease in pH (can fall to 6.4) caused by production of lactate
What is the effect of pH on PFK activity?
low pH activity diminishes PFK activity
During excessive activity or fasting, muscle tissue is degraded into what molecules? What are these molecules used for? (5)
muscle tissue degraded into amino acids → [alanine transaminase] → alanine → absorbed by liver → deaminated to form pyruvate → glucose via gluconeogenesis
In the resting state, what fraction of the resting muscle’s needs are met by fatty acid catabolism?
85%
(T/F) The heart always functions aerobically.
True
What are the possible fuels for the heart muscle?
fatty acids (fuel of choice)
ketone bodies (preferred over glucose)
lactate
What critical role does the kidney play in starvation conditions?
can produce up to half of the blood’s glucose via gluconeogenesis by using amino acid sources
The liver lacks what ketone body-related enzyme?
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
Glucose-6-phosphate is only found in which tissues?
liver
kidney
Amino acids are catabolized in what tissue?
liver
Enzymes associated with the urea cycle are only found in what tissue?
liver
kidney
What component of a triacylglycerol can actually be used as a glucose source?
glycerol moiety
Describe the metabolic changes associated with the transition from the fasting state to the starvation state. (4)
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
