Glycolosis/Gluconeogeneis - Dr. Bikman Flashcards
What is the only GLUT regulated by insulin?
GLUT 4
Where is the insulin regulated GLUT found?
Skeletal muscle, cardiac muscle, adipocytes
GLUTs move glucose _______ (up or down) its concentration gradient.
SGLTs move glucose ______ (with or against) its concentration gradient.
down
against
What type of cells synthesis insulin?
Pancreatic beta cells
What are 3 ways that blood glucose increases?
- Uptake from digestive tract
- Recovery from kidneys
- Release from the liver
When is insulin acutely elevated?
In anticipation of a meal and in the “dawn” phase/phenomenon
What are the two hormones in the dawn phenomenon that are antagonizing insulin?
Growth hormones and Cortisol
When is insulin chronically high?
Pre diabetes or diabetes
What is insulin’s affect on skeletal muscle?
Increases glucose uptake through GLUT 4’s - Anabolic effect
What is insulin’s affect on the liver?
Glucogenesis
Inhibition of Ketogenesis
Lipogenesis
What is insulin’s affect on adipocytes?
Glucose uptake
Lipogenesis
Adipogenesis
Overall, insulin ___________(reduces or increases) blood levels of glucose, fats and ketones.
reduces
What is the only major hormone that promotes fat storage?
Insulin
What is the only major hormone that inhibits fat use?
Insulin
Plasma _______ concentration is the primary regulator of insulin and glucagon release.
glucose
What are the primary catabolic regulators of glucagon?
Glucose, Growth hormone, Epinephrine/norepinephrine, and Cortisol
What is the only anabolic regulator of glucagon?
Insulin
What is the affect of an increase of glucagon on the muscle?
No affect because muscle has no glucose receptors
What is the affect of an increase of glucagon on the liver?
Gluconeogenesis
Ketogenesis
Glycogenolysis
What is the affect of an increase of glucagon on the adipose?
Lipolysis
Overall, glucagon ___________(reduces or increases) blood levels of glucose, fats and ketones.
Increases
Skeletal muscle uses glycolysis primarily for _________.
ATP production
The first step in glycolysis is the phosphorylation of glucose to ___________. This is a __________ (reversible or irreversible) reaction that utilizes ______(#) ATP.
Glucose 6 phosphate
irreversible
1
The enzymes involved in the first step of glycolysis are :
glucokinase and hexokinase
The second step in glycolysis is the isomerization of glucose 6 phosphate to __________. This is a __________ (reversible or irreversible) reaction. The enzyme involved in this reaction is _________.
Fructose 6 phosphate
Reversible
Phosphohexose isomerase
The third step in glycolysis is the kinase catalyzed phosphorylation of fructose 6 phosphate to ______________. This is a __________ (reversible or irreversible) reaction that utilizes ______(#) ATP. The enzyme involved in this reaction is _______.
fructose 1,6 biphosphate
irreversible
1
PFK-1
The fourth step of glycolosis can be highlighted by the conversion of a ___(#) carbon into two ____(#) carbon molecules. Specifically, fructose 1,6 bisphosphate to two sugars, dihydroxyacetone phosphate and glyceraldehyde 3 phosphate. These sugars are ______ of each other. The enzyme that catalyzes this reaction is __________. At the end of glycolysis one molecule of glucose is responsible for the production of two molecules of _______.
6
3
isomers
Aldose
Pyruvate
Step 5 of glycolysis takes the products of step 4 (dihydroxyacetone phosphate and/or glyceraldehyde 3 phosphate) and creates 1,3 bisphosophoglycerate. The highlight of this reaction is the production of _______ which can later be used in the electron transport chain. A molecule of ________ aids in this reaction.
NADH (*note, there are 2 NADH made in this step for each molecule of glucose)
inorganic phosphate
Step 6 of glycolysis takes 1,3 bisphosophoglycerate to 3 phosphoglycerate. This occurs by the transfer of phosphate resulting in _____ production. This process is known as ____ _____ ________. This results in the production of ___(#) ATP per glucose molecule. The enzyme in this reaction is ______ kinase.
ATP
Substrate level phosphorylation
2
phosphoglycerate kinase
Step 7 of glycolysis takes 3-phosphoglycerate to 2-phosphoglycerate by utilizing a specific type of isomerase known as a _________ which moves a phosphate from one atom to another. This is a _________ (reversible or irreversible) reaction.
mutase (phosphoglyceratemutase)
reversible
Step 8 of glycolysis is the removal of an _____ group form 2-phosphoglycerate creating PEP. The enzyme that catalyzes this ______ (reversible or irreversible) reaction is enolase.
OH
Reversible
Step 9 of glycolysis is the creation of ______ from PEP. This reaction utilizes the enzyme ________ _______. During this reaction ADP acquires a phosphate from PEP resulting in the creation of _____. This is a _________ (reversible or irreversible) reaction.
Pyruvate
Pyruate Kinase
ATP
irreversible
Where is pyruvate found in the cell?
Cytosol
How does pyruvate get into the mitochondria?
Pyruvate carrier
*Note: this is on the INNER mitochondrial membrane
What is the name of the complex that converts pyruvate to acetyl Co-A? What reducing equivalent is produced in this reaction?
Pyruvate dehydrogenase complex
NADH
Several ________ are required for conversion of pyruvate to acetyl Co-A. These include coenzyme A, NAD+, TPP, Lipoic acid and FAD.
Coenzymes
The pyruvate dehydrogenase complex is regulated by what two mechanisms?
Product inhibition
Phosphorylation/Dephosphorylation
What 3 products inhibit the pyruvate dehydrogenase complex?
Acetyl CoA
NADH
ATP
Phosphorylation of the PDC occurs by what enzyme?
Does phosphorylation inhibit or activate the complex?
Pyruvate dehydrogenase kinase
inhibits
Dephosphorylation of the PDC occurs by what enzyme? Does dephosphorylation inhibit or activate the complex?
Pyruvate dehydrogenase phosphatase
activates
True or False
The liver is capable of both glucose catabolism and anabolism.
True
How does the fact that glucokinase has a high Km affect glucose regulation in the liver?
Glucose is not phosphorylated unless glucose levels are high
Does high AMP (and low ATP) lead to glycolysis or gluconeogensis?
Glycolysis. If the cell has overall low energy (high AMP) then it desires glycolysis for energy production.
Two additional sites of regulation used by the liver are
fructose 2,6-bisphosphate and Phosphokinase phosphorylation. Both of these sites are regulated by ________ signaling.
hormonal
What three things does insulin induce the activity of in the fed state?
Glucokinase, PFK-1, and Pyruvate kinase
Insulin _______(induces or represses) the synthesis of GK, PFK-1, and PK in the liver in the fed state
Glucagon __________(induces or represses) the synthesis of GK, PFK-1, and PK in the liver in the fasting state
Induces
Represses
Describe the process that occurs after insulin binds to receptors on the liver that eventually leads to activation of PFK-1.
Insulin inhibits Fructose 2,6 bisphosphotase (the inhibitor) which increases fructose 2,6 bisphosphate which activates PFK-1.
The other way in which insulin regulates glycolysis is through pyruvate kinase ______ (phosphorylation or dephosphorylation).
dephosphorylation = active
The overall effect of insulin is an _________ (inactivation or activation) in glycolysis.
activation
Describe how glucagon acts on glycolysis to eventually lead to deactivation of PFK-1.
Glucagon activates adenylate cyclase which uses ATP to make cAMP. This cAMP increases PKA which phosphorylates fructose 2,6 bisphosphotase which decreases 2,6 bisphosphate, which in turn deactivates PFK-1.
The other way in which glucagon regulates glycolysis is through pyruvate kinase ______ (phosphorylation or dephosphorylation).
phosphorylation = inactive
↓ blood glucose = ↑ glucagon secretion = \_\_\_ cAMP = ↑ PKA activity = ↓ fructose-2,6bisP = \_\_\_ PFK-1 activity = ↓ glycolysis
↑
↓
↓ blood glucose = \_\_\_\_glucagon secretion = ↑ cAMP = \_\_\_\_ PKA activity = ↑ PK phosphorylation = \_\_\_\_PK activity = ↓ glycolysis
↑
↑
↓
The first bypass reaction of gluconeogenesis starts when acetyl Co-A builds up/doesn’t enter the CC. Describe the process that allows gluconeogenesis to proceed “up” the pathway.
- Acetyl Co-A is converted into oxaloacetate by pyruvate decarboxylase
- Oxaloacetate becomes Malate by the enzyme MDH.
- Malate is able to exit the mitochondira where it can be converted into oxaloacetate once again.
- PEPCK converts the oxaloacetate into PEP.
The second bypass reaction involves which enzyme?
Fructose 1,6 bpase
How is F2,6bpase regulated?
PFK 2 (a parallel enzyme to PFK 1) activates F2,6bp which inhibits F1,6bpase. In addition, F2,6pb will activate F2,6bpase which can be converted directly back to fructose 6 phosphate.
What do you think glucagon does to PFK-2?
What do you think glucagon does to F 2,6-bpase?
Activates it
Activates it
In the third bypass reaction glucose 6 phosphate is converted into _______ with the enzyme ____________. Where is this enzyme found within the cell?
glucose
glucose 6 phosphatase
Endoplasmic Reticulum
Does alanine inhibit or activate pyruvate kinase? Which process does this favor?
inhibits
gluconeogenesis
What other things can become pyruvate and thus be turned into glucose?
Lactate Alanine Cysteine Glycine Serine Tryptophan
What things can be converted into oxaloacetate in the mitochondria which can then be converted into pyruvate in the cytoplasm?
Asparagine
Aspartate
How can glycerol be used in glycolysis? Which step of the pathway and by what enzyme?
Glycerol can be converted into glyceraldehye 3 phosphate in step 4 by the enzyme glycerol kinase.
Why can’t we get glucose from fatty acids?
Acetyl Co-A cannot be converted back to pyruvate. The pyruvate dehydrogenase complex is not reversible.
Why can lipolysis increase glucose production?
The glycerol portion of the triglyceride can be used (once modified by glycerol kinase to glyceraldehyde 3 phosphate) in glycolysis.
Because fat isn’t a viable glucogenic substrate, it provides a replacement, which are ________.
Ketones
______ allows glycolysis to continue in anaerobic conditions by replenishing NAD.
Lactate
Describe the process by which lactate produces NAD for glycolysis.
Pyruvate is converted to lactate by the enzyme lactate dehydrogenase. This uses 2 NADH creating 2 NAD which are then put back into the glycolysis pathway.
What is the effect of lactate production on pH?
H+ is released in the conversion of NADH to NAD creating a more acidic environment
What are the 4 conditions discussed in class which produce anaerobic glycolysis?
- In red blood cells (no mitochondria)
- In working muscles
- During ischemia
- In tumor cells
Lactate produced by anaerobic glycolysis in RBCs and vigorously working skeletal muscle can be metabolized in at least three ways. Name these ways:
- It can be exported to resting skeletal muscle or the heart, which is rich in mitochondria and has a high oxidative capacity
Here, lactate is converted to pyruvate, which proceeds through the remaining steps of cellular respiration to provide energy in the form of ATP - It can be exported to the liver, where it is converted to pyruvate and used to regenerate glucose via gluconeogenesis
- It can be used by the very muscle that created it
The following definition describes what cycle?
The catabolism of glucose carbons to lactate in peripheral tissues, then anabolism of lactate to glucose at the liver
Cori Cycle
