Flashcards in Glycolysis and TCA Cycle Deck (55):
What determines the direction through the pathway (e.g., why glycolysis and not gluconeogenesis)?
Regulation of enzymes
Position of molecules (because molecular trapping can drive direction)
Investment of energy
Glycolysis begins with _________.
glucose being phosphorylated to glucose-6-phosphate in the cytosol (representing energy investment and molecular trapping)
Per Dr. Benessen, what are the three "key" regulatory steps in glycolysis?
(1) Glucose to glucose-6-phosphate
(2) Fructose-6-phosphate to fructose-1,6-bisphosphate ***rate-limiting***
(3) Phosphoenolpyruvate to pyruvate
What is the key regulated step in the TCA cycle?
Pyruvate to acetyl co-a (via loss of CO2)
Citrate performs what function?
It is a negative feedback signal.
What does the TCA cycle make?
The precursor that binds to acetyl co-a is _________.
Pyruvate to glucose is ___________.
The three steps that are regulated in gluconeogenesis are __________.
the same that are regulated in glycolysis
The first step that differs between glycolysis and glycogen formation is ___________.
glucose-6-phosphate gets isomerized to glucose-1-phosphate
What is the precursor molecule immediately before glycogen?
The regulatory step in glycogen formation is ___________.
UDP-glucose to glycogen
The regulatory step in glycogen breakdown is ___________.
glycogen to glucose-1-phosphate
HMS is ____________.
hexose monophosphate shunt
HMS forms ________ from glucose in states of excess (when glycogen stores are maxed out).
ribose (for purines and pyrimidines) and NADPH (energy source for synthetic reactions, particularly fat synthesis)
Gluconeogenesis has a funny step in the mitochondria, in which ______________.
pyruvate gets transformed to oxaloacetate, which itself gets transformed to phosphoenolpyruvate
The TCA cycle is primarily substrate driven, meaning ______________.
that consumption of ATP drives more production through the TCA cycle
What two cell types use glycolysis as their primary energy source?
RBCs and sperm
List the reactants in the glycolysis pathway.
(Hexokinase or glucokinase)
(Glyceraldehye 3-phosphate dehydrogenase)
What are the two classic tissues that are insulin sensitive?
Skeletal muscle and adipose tissue
The insulin-inducible glucose channel is ____________, while the constitutive glucose channel is __________.
What is substrate-level phosphorylation?
Phosphorylation of ADP to ATP by enzymes in the TCA (whereas oxidative phosphorylation is the use of ATP synthase and proton gradient)
What three things are accomplished by the initial phosphorylation of glucose?
(1) Glucose becomes trapped in the cell.
(2) Glucose stores energy and is more able to move to the next step in glycolysis.
(3) The enzyme that next handles glucose interacts with the phosphate group and the energy of activation is lowered.
Hexokinase is present in _____________, while glucokinase is present in _____________.
all tissues; the liver and pancreatic beta-cells
Why is it favorable to have glucokinase in the liver?
Glucokinase has a higher Km than hexokinase. This means that when glucose levels are high, the liver is able to phosphorylate more glucose than other tissues, an effect that traps glucose in hepatocytes (where it will be converted to glycogen). Similarly, when glucose levels are low, less glucose will be phosphorylated in hepatocytes and the liver thus releases glucose.
True or false: phosphorylation of glucose and fructose 6-phosphate are reversible reactions.
False. Both are irreversible.
Phosphofructokinase is allosterically inhibited by _______________ and stimulated by __________.
ATP and citrate; AMP
Under the high-insulin, low-glucagon (fed) state, describe what happens to the PKA PFK-2 pathway.
High-insulin, low-glucagon states lead to decreased activity of protein kinase A (PKA), because of decreased cAMP. PKA normally phosphorylates (thus deactivating) phosphofructokinase-2 (PFK-2). Having less PKA therefore leads to more active PFK-2. PFK-2 creates fructose 2,6-bisphosphate, which potently activates phosphofructokinase-1, thereby stimulating glycolysis.
_____________ is the most potent activator of PFK-1.
Fructose 2,6-bisphosphate (this can activate PFK-1 even when ATP is high)
Fructose 2,6-bisphosphate inhibits _____________.
fructose 1,6-bisphosphatase (an important enzyme in gluconeogenesis)
True or false: when glucagon is high and insulin is low, a different enzyme than PFK-2 removes the phosphate from the 2-position of fructose.
False. PFK-2 is bidirectional, and when glucagon is high and insulin is low, PKA is activated and phosphorylates PFK-2. The phosphorylated form is a phosphatase that removes the 2-phosphate from fructose.
What is important to remember about the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase?
It is the first to create NADH in glycolysis!
What is noteworthy about the reaction 1,3-bisphosphoglycerate (x1) to 3-phosphoglycerate (x2)?
It is the first reaction to produce ATP; it produces two molecules of it, and thus brings the net ATP to zero.
What enzyme catalyzes the first reaction to have substrate-level phosphorylation in glycolysis?
Phosphoglycerate kinase (being the reaction from 1,3-bisphosphoglycerate to two molecules of 3-phosphoglycerate)
The first enzyme to produce net positive ATP from glycolysis is ____________.
pyruvate kinase (bringing the total to +2 molecules of ATP)
What stimulates the reaction catalyzed by pyruvate kinase?
What inhibits pyruvate kinase?
ATP and protein kinase A (by phosphorylating it)
During fasting, the body wants to turn off _________ and turn on _____________.
In the presence of _______, pyruvate will be converted to acetyl co-a.
Why is pyruvate converted to lactic acid?
Because this oxidizes NADH to NAD+. This is necessary, because NAD+ is used to oxidize glyceraldehyde 3-phosphate to 1,3-bisphosphate. Without the NAD+ generated from the pyruvate to lactate conversion, glycolysis would stop and the cell would be totally without energy sources.
Why do the liver and heart convert lactate to pyruvate?
Because the NADH/NAD+ ratio is much lower, driving the conversion of lactate to pyruvate, which can go into the TCA cycle and generate CO2, H2O, and ATP.
In the fed state, pyruvate can be converted to ___________.
alanine for protein synthesis or fatty acid synthesis
What happens to pyruvate in the liver during a fasting state?
It is converted to oxaloacetate for substrates for gluconeogenesis.
True or false: pyruvate gets converted to acetyl co-a in the cytosol.
False. Pyruvate dehydrogenase is in the mitochondria.
What things inhibit pyruvate dehydrogenase?
NADH and acetyl co-a (the immediate product and a downstream product)
Why does thiamine deficiency lead to neurologic symptoms?
Because pyruvate oxidation is crucial for brain function, and thiamine is a cofactor for this reaction.
High levels of _______________ in the blood are diagnostic of thiamine deficiency.
What organ needs to inhibit pyruvate dehydrogenase?
The liver, so that pyruvate can be re-directed to gluconeogenesis
Remember what Dr. Bessesen says: in the fed state, insulins causes proteins to be _____________.
Pyruvate dehydrogenase is active when ________________ (a covalent modification).
The enzyme that inhibits pyruvate dehydrogenase is stimulated by _______________ and inhibited by _____________.
What enzyme catalyzes the first reaction of the TCA cycle?
Citrate synthase, which unites oxaloacetate and acetyl co-a
Citrate is a feedback inhibitor of _______.
List the substrates and enzymes of the TCA cycle.
Oxaloacetate + acetyl co-a
(Isocitrate dehydrogenase) ***CO2 an NADH produced***
(Alpha-ketoglutarate dehydrogenase) ***CO2 and NADH produced***
(Succinate thiokinase) ***GTP produced***
(Succinate dehydrogenase) ***FADH2 produced***
(Malate dehydrogenase) ***NADH produced***