Unit 11 Flashcards
What is meant by the term gluconeogenesis?
- The biosynthesis of a carbohydrate from simpler, noncarbohydrate precursors such as oxaloacetate or pyruvate
*converts pyruvate and related 3-4 carbon compounds into glucose
Why is gluconeogenesis important in animals?
This process is important because some tissues depend almost completely on glucose for their metabolic energy and unfortunately, the supply of glucose from these stores is not always sufficient (between meals and fasting)
In what tissues does it mainly occur?
Usually occurs in the liver
Name three non-carbohydrate precursors of glucose
Pyruvate
Glucogenic amino acids
Triacyl-glycerols/glycerols
What does lactate turn into?
Pyruvate and then into the TCA cycle
What do glucogenic amino acids turn into?
Nothing, they just enter the TCA cycle
What do triacyl-glycerols turn into?
Glycerol and then they enter the TCA cycle
Why does gluconeogenesis require a pathway different than the reversal of glycolysis?
- Because there are three reaction son glycolysis that are essentially irreversible and cannot be used in gluconeogenesis: the conversion of glucose to glucose-6-phosphate by hexokinase, the phosphorylation of fructose 6-phosphate into fructose- 1,6- phosphate by phosphofructokinase-1, and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase
Which steps of glycolysis are irreversible?
the conversion of glucose to glucose-6-phosphate by hexokinase, the phosphorylation of fructose 6-phosphate into fructose- 1,6- phosphate by phosphofructokinase-1, and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase
Bypass 1
Conversion of pyruvate to phosphoenolpyruvate (PEP)
Using structures, write balanced equations for the reactions involved
Pyruvate + ATP + GTP + HCO3- –> PEP + ADP + GDP + Pi + CO2
Name the cofactor used by pyruvate carboxylase and describe its function
Biotin. Biotin transfers CO2 from Site 1 to Site two so it can meet with pyruvate to form oxaloacetate
What is the role of ATP in the conversion of pyruvate?
To turn HCO3- into CO2
Draw the creation of oxaloacetate using pyruvate carboxylase
In this series of reactions, pyruvate is first carboxylated to oxaloacetate and then decarboxylated to phosphoenolpyruvate. Why is this series of steps important?
This carboxylation-decarboxylation sequence represents a way of activating pyruvate, in that the decarboxylation of oxaloacetate facilitates PEP formation
Discuss two alternate pathways from pyruvate to phosphoenolpyruvate. What is the purpose of the variation in the pathway from pyruvate?
NADH and H+ are required to be made in the cytosol. Since starting from lactate will generate NADH in the cytosol when it turns into pyruvate, it can generate PEP in the mitochondria. However, if you start with pyruvate, you must take extra steps to convert oxaloacetate to malate and back to oxaloacetate just to generate NADH in the cytosol
Write a balanced equation for the reaction catalyzed by fructose 1,6-bisphosphatase (FBPase-1). Name the type of reaction
Fructose 1,6-phosphate + H20 –> Fructose 6-phosphate +Pi
HYDROLYSIS REACTION
Write a balanced equation for the reaction catalyzed by glucose 6 phosphate. Name the type of reaction
Glucose 6-phosphate + H20 –> glucose + Pi
HYDROLYSIS REACTIOn
Summarize the bioenergetics of glycolysis and gluconeogenesis
glucose –> 2 pyruvate +2 ATP
2 pyruvate –> glucose -6 ATP
Account for the 6 ATPs required for gluconeogenesis. Remember that we are dealing with the conversion of two moles of pyruvate and that energetically, ATP and GTP are equibalent
- 2 ATPs are used by pyruvate carboxylase (to go from pyruvate to oxaloacetate)
- 2 GTPs are used by PEP carboxykinase to go from Oxaloacetate to PEP
- 2 ATPs are used by 3-Phosphoglycerate to turn into 1,3-Bisphosphoglycerate
Which other step in gluconeogenesis can be described as an energy input?
1,3-Bisphosphoglycerate –> (2) Glyceraldehyde 3 phosphate
Why would it be wasteful for a cell to simultaneously carry out both glycolysis and gluconeogenesis? How is this prevented?
It would be wasteful because glycolysis only generates 2 ATPs while gluconeogenesis uses up 6 ATPs. If both cycles were to go at the same time, you would lose 4 ATPs which is not effective. This process is prevented through reciprocal regulation
Discuss the reciprocal regulation of PFK-1 and FBPase-1 by AMP (DRAW THIS WHOLE DIAGRAM)
When AMP levels are high, it drives the activation of PFK-1 and inhibits the activation of FBPase-1. This encourages glycolysis and limits FBPase-1 so that gluconeogenesis isn’t occuring
Discuss the reciprocal regulation of PFK-1 and FBPase-1 by fructose 2,6-bisphosphate (DRAW SIMRITA’S DIAGRAM)
Discuss how/when fructose 2,6-bisphosphate accumulates in the cell (DRAW BOTH DIAGRAMS)
Fructose 2,6-bisphosphate is regulated by the enzymes insulin and glucagon which control PFK-2 and FBPase 2. Insulin activates glycolysis and inhibits gluconeogenesis. Glucagon activates gluconeogenesis and inhibits glycolysis
Insulin REMOVES a phosphate group from the PFK-2 and FBPase-2 to activate the PFK-2 and stimulate glycolysis. Glucagon adds a phosphate group to the complex to activate FBPase and inhibit PFK-2
Discuss the reciprocal regulation of pyruvate carboxylase and the enzyme that prepares pyruvate for entry into the citric acid cycle, pyruvate dehydrogenase (DRAW DIAGRAM)
When pyruvate turns into acetyl-CoA, an enzyme called pyruvate dehydrogenase facilitates that pathway. When pyruvate is converted into oxaloacetate, that is done by pyruvate carboxylase and activates gluconeogenesis. Production of acetyl-CoA is the commitment to entering the citric acid cycle. When there is too much acetyl-CoA, it will inhibit the production of pyruvate dehydrogenase so no more of it can be made. It will also upregulate pyruvate carboxylase to promote gluconeogenesis
What is teh name of the enzyme complex that forms acetyl-CoA from pyruvase?
PDH complex
Write the net reaction catalyzed by the pyruvate dehydrogenase complex (DRAW IT OUT)
Pyruvate + CoASH + NAD+ + TPP + lipoate + FAD –> CO2 + Acetyl-CoA
How many coenzymes are involved in the conversion of pyruvate to acetyl-CoA?
5:
- TPP
- lipoate
- FAD
- NAD+
- CoA-SH
How many enzymes are involved in the conversion of pyruvate to acetyl-CoA?
3 enzymes:
E1, E2, E3
Discuss “substrate channeling”. What is the advantage of having these enzymes organized into a complex
Movement of the chemical intermediates in a series of enzyme-catalyzed reactions from the active-site of one enzyme to that of the next enzyme in the pathway. This is advantageous because the rate increases and it prevents the loss of intermediates
What is the function of FAD and NAD+ in the reaction pathway. Does it seem odd that FADH2 is strong enough to reduce NAD+ to NADH? Explain how this is possible
DRAW STEP 1 OF CITRIC ACID CYCLE
Claisen Condensation
Enzyme that catalyzes this reaction: Citrate synthase
Acetyl-CoA + Oxaloactate –> Citroyl CoA –> Citrate
DRAW STEP 2 OF CITRIC ACID CYCLE
Dehydration, Rehydration
Enzyme that catalyzes this reaction: Acoritase
Citrate (-H20) –> Cos-Acoritate –> (+H20) isocitrate
`
*OH is added to a different carbon
DRAW STEP 3 OF CITRIC ACID CYCLE
Dehydrogenation
Enzyme that catalyzes this reaction:
Isocitrate dehydrogenase
Isocitrate + NAD+ –> NADH + CO2(-) + alpha-ketoglutarate
DRAW STEP 4 OF CITRIC ACID CYCLE
Oxidative decarboxylation
Enzyme that catalyzes this reaction:
alpha-ketoglutarate dehydrogenase complex
Alpha-ketoglutarate + NAD+ + CoA-SH –> succinyl CoA
How can one explain the ability of an enzyme to distinguish between the two ends of a compound like citrate?
Aconitate has 3 binding points that isocitrate can bind to. If the molecule is still symmetrical, it will not be able to bind to the site properly. So it will only be able to properly bind the other way
List the four oxidation reactions of the citric acid cycle and tell which coenzymes picks up electrons and H atoms released in each of these rxns
- Isocitrate –> alpha-ketoglutarate (NAD)
- Alpha-ketoglutarate –> succinyl CoA (NAD)
- Succinate –> Fumarate (FAD)
- Malate –> Oxaloacetate (NAD)
What eventually happens to these electrons and H atoms?
They enter the electron transport chain
How many molecules of reduced coenzymes are produced from one molecule of glucose?
10 NADH
2 FADH2
4 ATP
In the cell, the citric acid cycle is an important catabolic pathway. Name the three classes of molecules that undergo their final oxidation in the citric acid cycle
Fats, carbohydrates, and proteins
List the anabolic functions of the citric acid cycle
Citrate –> fatty acids, sterols
Alpha-ketoglutarate –> purines, amino acids
Succinyl CoA –> heme
Oxaloacetate –> pyrimidines, amino acids
PEP –> Glucose and amino acids
Define anaplerotic reaction and explain the metabolic importance of the above reaction
- An enzyme-catalyzed reaction that can replenish the supply of intermediates in the citric acid cycle
- This is important bc if all of the intermediates were used up, we would be unable to make oxaloacetate - the goal
