Flashcards in METABOLISM QUIZ 1 Review Questions Deck (24)
Epinephrine causes increased glycolysis when muscle glycogen is broken down to glucose-6-phosphate, but epinephrine inhibits glycolysis when liver glycogen is broken down to glucose-6-phosphate. Explain.
Muscle breaks down glycogen to use glucose for its own glycolysis.
Liver conversely breaks down glycogen to glucose and exports the glucose to other tissues/cells.
In the case of high epi, this is a fight or flight situation, and muscle needs energy.
Liver thus is supplying other tissues that are important to the fight/flight response with the glucose they need to produce energy via glycolysis.
Epi also causes the cAMP cascade in the liver; this activates protein kinase A; protein kinase A activation inhibits Pyruvate Kinase. This means no glycolysis.
This inhibition of PK only happens in the liver, not in the muscle.
What would addition of arsenic do to RBCs, in the presence of glucose, with respect to the amount of ATP made per glucose? With respect to the rate of lactic acid formation?
Arsenic inhibits the G3PDH step of glycolysis.
RBCs only do glycolysis to form ATP.
You would thus get a lower amount of ATP.
Arsenic competes with phosphate to get added to G3P to make 1,3bPG.
The RBC could still form lactate because the 1,3bPG intermediate would not be formed, and instead energy would be released as heat, but then glycolysis could continue forward to make pyruvate which can become lactate.
A pyruvate kinase deficiency of the RBC leads to anemia. The RBCs will have elevated levels of fructose 1,6 bis phosphate. Explain.
Fructose 1,6 bis phosphate will build up because if PK is deficient, the reaction will proceed in the opposite direction up until the last irreversible reaction.
Anemia occurs because the net ATP made is 0.
Explain the observation that pyruvate dehydrogenase deficiency exhibits lacticacidemia that in some patients is responsive to high doses of thiamine.
All of your pyruvate will become lactate if you don’t have PDH because this is the other fate of pyruvate that can occur.
If the patient is deficient in E1, adding thiamine would cure this patient because that is the cofactor of E1 which is part of PDH.
Pyruvate carboxylase deficiency is a rare metabolic disorder in infants and children, which most often is fatal early in life. What is so critical about this enzyme? What might you recommend with respect to an optimal diet to support such patients?
This is fatal because pyruvate carboxylase is an enzyme responsible for the analproetic reaction that regenerates OAA when OAA is deficient in the TCA cycle. If you didn’t have this, wouldn’t get energy production.
It is also an enzyme important in gluconeogenesis.
Without it you cannot eat glucose.
Why would a liver glucose-6-phosphatase deficiency result in a more pronounced hypoglycemia than a deficiency in other liver glycogen breakdown enzymes?
G-6-phosphatase is present in liver, absent in other tissues.
G-6-Pase de-phosphorylates G6P, helping release glucose into the bloodstream.
If the G6P isn’t de-phosphorylated, then glucose will be withheld.
So Liver helps to regulate blood glucose level by degrading liver glycogen stores.
Would administration of caffeine cause a rise in blood glucose in an individual lacking functional glucagon receptors? Would it lead to glycogen breakdown in muscle?
Caffeine inhibits phosphodiesterase.
PDEs cleave cAMP-PKA signal
If PDE is inhibited, then get constitutive signaling per glucagon/epi signals
This would lead to glycogen breakdown only in liver, though, because there aren’t glucagon receptors in muscle – only epi.
The phosphorylated form of glycogen synthase is the less active form. How can it be activated allosterically, without dephosphorylation? What is the physiological rationale for this mode of activation?
Can activate glycogen synthase allosterically by G6P
G6P is thus active when high blood glucose leads to elevated intracellular G6P
As a result, glycogen is active
Glucose-6-phosphate dehydrogenase (G6PD) deficiency leads to symptoms only upon exposure of affected individuals to oxidant agents. Why doesn’t a deficiency in NADPH production by G6PD-deficient individuals cause defects in fatty acid biosynthesis and other syntheses required for development?
Because the isocitrate shuttle can be used to shuttle NADPHs from mito to cyto for FA synthesis
RBC though do need NADPH to regenerate GSH in the face of oxidant agents
Malic enzyme supplies NADPH for FA biosynthesis in other organs
What is the special role of G6PD in the RBC?
G6PD is needed in the PPP to produce NADPH
NADPH is used to regenerate Glutathione cofactor which is needed to reduce H2O2 to H2O and avoid damage from oxidative stress
In the growing child, whose need for pentose phosphates exceeds the rate of production via glucose-6-phosphate → 6-phosphogluconate → pentose phosphates, how are more produced?
More G6P are produced from F6P, by doing the “rearrangement reactions” in reverse.
Patients with severe carnitine-acylcarnitine carrier deficiency exhibit: (i) hypoglycemia that is accompanied by lower than normal ketone body levels rather than higher; and (ii) abnormal liver functions with fatty globule accumulation in the tissue. Explain these symptoms.
If don’t have the carnitine carrier, then fatty acyl CoA cannot get transported into the inner mito embrane for FA synthesis. This is requisite on the path to ketone body synthesis; ketone body synthesis occurs when there’s extra acetyl CoA from FA synthesis that needs to be used.
Fatty globules accumulate in this person’s liver tissue because of overproduction of FA, not breaking them down at all.
The following enzymes would all decrease in level during prolonged starvation: glucokinase, citrate lyase, malic enzyme and fatty acid synthase. Explain.
All of these enzymes are involved w/ FA synthesis. When you’re starving, you want to break down fatty acids, to use as energy, not build them up.
During periods of starvation, your body does gluconeogenesis (glucokinase) / FA break down (fatty acid synthase) / malic enzyme ( ) / FA production (citrate lyase, part of the citrate shuttle that moves acetyl CoA into the cytoplasm for FA synthesis).
How does a high-energy state in the mitochondrion lead to suppression of glycolysis and fostering of fatty acid biosynthesis in the cytoplasm?
High energy state in the mito would suppress glycolysis because glycolysis produces energy by metabolizing glucose into pyruvate; do not need this to happen if in a high energy state inside the mito.
FA synthesis occurs in a high energy environment, when want to sequester and store energy as FA for when you need energy to be released.
Under conditions in which ketone bodies are synthesized by the liver and, to some extent, by the kidney, they can be broken down for entry into the Krebs cycle in muscle and brain. Explain what condition leads to their formation. Why just in the liver? How can they be utilized by the other tissues under those same circumstances?
Ketone body formation occurs when have excess acetyl CoA that cannot undergo TCA cycle, aka because OAA has been depleted per gluconeogenesis. Starvation state or diabetic ketoacidosis lead to ketone bodies’ formation. When B-oxidation of fats occurs and acetyl CoA is produced, we will run out of CoA to use for metabolism; ketogenesis reproduces that CoA.
This occurs only in the liver’s mito.
Would you expect fatty acid biosynthesis to be impaired in a severely pantothenic acid-deficient individual?
Pantothenic acid = Vitamin B5
This matters for ??
Explain why the B vitamin biotin is necessary for fatty-acid synthesis.
Biotin is the cofactor for several important enzymes in metabolism. In FA synthesis, it’s the cofactor for proprionyl CoA carboxylase, which is vital in converting proprionyl CoA into succinyl CoA during B-oxidation of an odd-chained fatty acid. Biotin’s also the cofactor for acetyl CoA carboxylase, which is the enzyme that metabolizes acetyl CoA into Malonyl CoA which is crucial for Faty Acid synthesis.
function of catabolism? anabolism?
catabolism: breaking down larger macromolecuels into smaller, simpler compounds
anabolism: enzymatic synthesis of large macromolecules from smaller, simpler precursors
what's the rate limiting enzyme of a metabolic pathway?
enzyme that catalyzes the slowest conversion will control the rate of the entire pathway
what are some criteria to show whether a substrate is transported into cells by a carrier-mediated mechanism
can inhibit the carrier and see if the substrate's activities are still carried out in the cells. if not then know the carrier is bringing the substrate into the cell
if don't know carrier's identity, could measure rate of cellular uptake, based on hormone modulation - insulin, glucagon, epi
what types of glucose transport mechanisms can occur in cells?
active (glut 5)
passive (glut 1, 2, 3, 4)
low Km (glut 1, 3)
high Km (glut 2)
move from inside of cell to plasma membrane by signal (glut 4)
how would a mutation that changes tyrosine residues in the insulin receptor to phenylalanine affect actions of insulin?
would inhibit insulin’s actions. Need to have phosphorylation via receptor’s tyrosine residues in order to phosphorylate IRB1 and 2 and other proteins that’re recruited, and in turn, to phosphorylate downstream targets and carry out insulin’s effects in the cell
no downstream actions of insulin -> diabetes-like presentation
why is diabetes 'starvation in the midst of plenty'
because cells are starving in a sea of glucose. Cells with Glut4 receptors (largely muscle and fat cells), especially, cannot take up glucose even as the levels are higher and higher. So, those cells starve and are unable to convert glucose to energy and other intracellular products despite its high plasma concentration