Glycolysis/Gluconeogenesis (complete) Flashcards
What transports glucose from the lumen of the intestines and kidney into the epithelial cells
SGLT
what kind of transport do SGLTs do
active transport
what is is required for SGLTs to be able to transport glucose against its concentration gradient
sodium in the lumen (it goes with its concentration gradient, and brings glucose with it against glucoses own concentration gradient)
What happens if you have a completely sodium free diet
you will eventually lose the ability to absorb glucose into the epithelial cells of the kidney and intestines.
What types of transporters transport glucose from inside the epithelial cells into the blood
GLUT transporters
what kind of transport do GLUTs do
they do passive transport
Where are GLUTs located
in all cells of the body, on the side of the cell bordering the capillaries
Which GLUT is regulated by insulin
GLUT 4
Where is GLUT 4 located
- skeletal muscle cells (myocytes)
- Cardiac muscle cells (cardiomyocytes)
- Fat cells (adipocytes)
Which GLUTs aren’t regulated by insulin
1-3 and 5-13
Where is insulin synthesized
pancreatic beta cells
what is insulin
a small peptide hormone
What happens to glucose immediately after it leaves the blood and enters into a cell
it is phosphorylated into glucose-6-phosphate
why is glucose immediately phosphorylated upon entrance into a cell
- so that it is “trapped” in that cell and won’t leave
- so that it won’t affect the concentration gradient of glucose and glucose will still be able to passively enter the cell
When insulin is synthesized, what is the other byproduct of it’s synthesis that can be used to test the production of insulin
C peptide
What are the normal levels of blood glucose
75-100 mg/dL
What are the three ways to increase blood glucose
- glucose absorption in the gut
- Glucose recovery from the kidneys
- glucose release from the liver
How does insulin allow GLUT-4 to transport glucose from the blood into muscle, fat, and cardiac muscle cells
insulin binding to its receptor causes the translocation of GLUT from inside the cell to the cell membrane
What is glucose clearance
glucose being taken out of the blood and transported into the tissues
What is the primary action of insulin
to cause glucose clearance (uptake of glucose from the blood and into the cells)
What does the enzyme phosphatase do
it dephosphorylates Glucose-6-Phosphate to glucose in the liver
where is phosphatase found
in the liver only
the lack of what enzyme in skeletal muscle is the reason why skeletal muscle doesn’t release glucose back into the blood
the lack of phosphatase
Through what transporter does glucose leave the liver and enter the bood
GLUT-2
Can muscle cells uptake glucose even when insulin is not present
yes
what stimulates glucose uptake in muscles when insulin is not present
muscle contaction
what is the process by which muscle contraction in skeletal muscle causes the uptake of glucose.
- Contraction uses ATP, and gives off ADP
- ADP is used to make more ATP and AMP
- High levels of AMP in the cell stimulates AMPK
- AMPK stimulates GLUT-4 to move to the cell membrane of muscle cells
When is insulin high, acutely
- after a meal
- in anticipation of a meal
- in the morning
When is insulin high chronically
insulin resistance (pre-diabetes) or diabetes
What is the effect of the sympathetic nervous system on insulin and glucagon
decreases insulin and increases glucagon
what is the effect of the parasympathetic nervous system on insulin and glucagon
increases insulin and decreases glucagon
What does insulin do in muscle tissue
- increases glucose uptake
2. helps in anabolism (building up of muscle)
What does insulin do in the liver
- inhibits ketogenesis
- activates lipogenesis
- activates glycogenesis
What does insulin do in adipose tissue
- causes glucose uptake
- activates lipogenesis
- activates adipogenesis
What levels in the blood are decreased with the release of insulin
- glucose
- fats
- Ketones
Along with insulin, what are the other major hormones that promote fat storage and inhibits fat usage
None, insulin is the only major hormone that promotes fat storage and inhibits the use of fats
how easy is it to gain fat without insulin
nearly impossible
What hormones counter the affect of insulin on fats (Which ones cause the breakdown and usage of fats?)
- glucagon
- catecholectamines
- cortisol
- Growth Hormone (GH)
What is the affect of glucagon, cortisol, catecholectamines, and growth hormone on blood glucose levels
they increase blood glucose levels
Are glucagon, cortisol, catecholectamines, and GH catabolic or anabolic
catabolic
what is the effect of insulin on blood glucose levels
it decreases blood glucose levels
is insulin catabolic or anabolic
anabolic
What is the primary regulator of insulin and glucagon
plasma glucose concentration
plasma glucose concentration is the primary regulator of insulin and glucagon. what happens when it’s high, what happens when it’s low
When it is high, insulin is secreted and glucagon isn’t
When it is low glucagon is secreted and insulin isn’t
What is the effect of glucagon on muscle tissue
there is no effect
why doesn’t glucagon have an effect on muscle tissue
because there are no glucagon receptors in muscle tissue
What is the effect of glucagon on the liver
- glycogenolysis
- gluconeogenesis
- ketogenesis
What is the effect of glucagon on adipose tissue
Lipolysis
Which types of cells don’t have glucagon receptors?
- adipocytes
- myocytes
- hepatocytes
myocytes - muscle cells
Which types of cells don’t have insulin receptors
- adipocytes
- myocytes
- hepatocytes
All cells have insulin receptors
What are the molecules and enzymes (E:) of glycolysis
1 Glucose
E: Hexokinase (glucokinase)
2 Glucose-6-Phosphate
E: Phosphohexose Isomerase
3 Fructose-6-phosphate
E: Phosphofructokinase-1 (PFK-1)
4 Fructose-1,6-Bisphosphate
E: Aldolase (cuts the 6-C molecule into 2 3-C molecules)
5 Glyceraldehyde - 3 phosphate (2)
E: Glyceraldehyde-3-phosphate dehydrogenase
6 1,3-bisphosphoglycerate (2)
E: phosphoglycerate kinase
7 3-phosphoglycerate (2)
E: phosphoglycerate mutase
8 2-phosphoglycerate (2)
E: Enolase
9 Phosphoenolpyruvate (PEP) (2)
E: Pyruvate kinase
10 Pyruvate (2)What portion of glycolysis is referred to as the preparatory phase
From the start, up until the 6 carbon molecule splits into two 3 carbon molecules
Why are the first few steps (up until the splitting point) called the preparatory phase
because up until this point, energy has only been used, no energy has been given off
What is the payoff phase of glycolysis
the second half of glycolysis, after the 6 carbon molecule splits, up to the creation of pyruvate
why is the second half of glycolysis referred to as the payoff phase
because it is in the second half of glycolysis that NADH and ATP are created
how many ATP are created for each glucose molecule that goes through glycolysis, how do you get this number?
4, ,
one is created during the phophoglycerate reaction of 1,3 bisphosphoglycerate into 3 phosphoglycerate.
the second is created during the pyruvate kinase reaction of PEP into pyruvate
So two for each 3 carbon molecule that goes through the second half of glycolysis, and each glucose molecule ends up sending two 3 Carbon molecules through the second half of glycolysis
How many NADH are created for each glucose molecule that goes through glycolysis. How do you get this number
2.
one is created during the glyceraldehyde-3-phosphate dehydrogenase reaction of glyceraldehyde-3-phosphate into 1,3-bisphosphoglycerate
(but because this reaction occurs twice per glucose molecule, you get two total NADH from one glucose molecule)
What is the Actual net ATP gain from glycolysis
2 ATP, the 4 created in the second half of glycolysis minus the two reactions that use ATP in the first half of glycolysis
What are the reactions in glycolysis that use ATP
- The Hexokinase/Glucokinase reaction of glucose into glucose-6-phosphate
- The PFK-1 reaction of fructose-6-phosphate into fructose-1,6-bisphosphate
Which two steps in the preparatory phase of glycolysis add a phosphate to the molecule
- the hexokinase/glucokinase reaction
2. the PFK-1 reaction
what is significant about the location of the phosphate that is added in the PFK-1 reaction
it is added to the #1 carbon (which is opposite to the phosphate added by glucokinase/hexokinase to the #6 carbon) this allows the glucose molecule to split into two identical molecules
Which steps in glycolysis are irreversable
Step 1. Glucokinase/hexokinase
Step 3. phosphofructokinase-1 (PFK-1)
Step 9. Pyruvate kinase
How many pyruvate are formed in glycolysis from each molecule of glucose
2
Where does pyruvate go after it is formed in glycolysis
to the mitochondra
How does pyruvate enter the inner membrane of the mitochondria
through a pyruvate carrier
Pyruvate gets converted to what molecule in the mitochondria
Acetyl-CoA
What is the enzyme that converts pyruvate into Acetyl-CoA
the pyruvate dehydrogenase complex
What are all of the products created in the pyruvate dehydrogenase complex reaction
- Acetyl-CoA
- NADH
- CO2
High Levels of what lead to deactivation of the pyruvate dehydrogenase complex
- ATP
- NADH
- Acetyl-CoA
What are the 5 cofactors that are needed for the pyruvate dehydrogenase complex to work
- Coenzyme A
- NAD+
3, TPP - Lipoic Acid
- FAD
Besides the high levels of ATP, NADH, and Acetyl-CoA what inhibits the pyruvate dehydrogenase complex
Phosphorylation by pyruvate dehydrogenase kinase
What dephosphorylates the Pyruvate dehydrogenase complex, and does that activate it, or inactivate it
pyruvate dehydrogenase phosphatase, and this activates it
What is the primary reason that the liver runs glycolysis
to convert glucose into glycogen and fat
What are the regulators of glycolysis
- Glucose
- ATP
- AMP
- Fructose, 2-6-bisphosphate
- PK phosphorylation
- Fructose-1,6-bisphosphate
How does ATP regulate glycolysis
High levels of ATP indicate that the cell has plenty of energy, and so it inhibits glycolysis. It does this at PFK-1
and at the PK
What are the two places that ATP acts on in inhibiting glycolysis
- PFK-1
2. PK
How does glucose regulate glycolysis
glucose is the initial substrate of glycolysis, and at least in the liver glucokinase is the first enzyme to act on glucose. it has a high Km, or low affinity for glucose, so if glucose levels are low, then glycolysis activity is low. is glucose is high, glycolysis levels are high
How does AMP regulate glycolysis
AMP is made by breaking down ATP. so it is high when energy is being used, and it is low when energy isn’t being used. So if AMP is low, then it will inhibit glycolysis.
At which places does a low level of AMP regulate glycolysis
PFK-1
How does Fructose-2,6-bisphosphate regulate glycolysis
Fructose-2,6-bisphosphate is a product of PFK-2, which runs side by side of PFK-1. Fructose-2,6-bisphosphate activates PFK-1.
What enzyme leads to creation of fructose-2,6-bisphosphate. and what is the initial substrate this enzyme uses
PFK-2 is the enzyme that converts fructose-6-phosphate into fructose-2,6-phosphate.
We know that the product of PFK-2 (fructose-2,6-bisphosphate) activates PFK-1. but what are the regulators of PFK-2
insulin
glucagon
What are the three locations of glycolysis that are regualted by insulin and glucagon
Glucokinase
PFK-1
Pyruvate Kinase
What is the effect of insulin on glucokinase, PFK-1 and pyruvate kinase
insulin activate glucokinase, PFK-1, and Pyruvate kinase
When is insulin present, and able to activate glycolysis
in a fed state
what is the effect of glucagon on glucokinase, PFK-1, and pyruvate kinase
glucagon represses activity of glucokinase, PFK-1, and pyruvate kinase
When is glucagon present, and able to repress glycolysis
in a fasting state
How does insulin affect Glucokinase
it helps to stimulate its creation, and release from the nucleus
how does glucagon affect glucokinase
it represses its activity
how does insulin affect PFK-1
- PFK-2 creates and increases fructose-2,6-bisphosphate levels
- fructose-2,6-bisphosphate activates PFK-1
- fructose-2,6-bisphosphatase takes fructose-2,6-bisphosphate and turns it back into fructose-6-phosphate
- insulin inactivates fructose-2,6-bisphosphatase, keeping fructose-2,6-bisphosphate levels high, which increases PFK-1
so insulin activates PFK-1
how does glucagon affect PFK-1
- glucagon activates adenylate cyclase
- adenylate cyclase creates cAMP
- cAMP activates PKA
- PKA phosphorylates and activates fructose-2,6-bisphosphatase
- fructose-2,6-bisphosphatase turns fructose-2,6-bisphosphate into fructose-6-Phosphate
- decreased levels of fructosr-2,6-bisphosphate leads to deactivation of PFK-1
Glucagon decreases PFK-1 activity
How does insulin affect Pyruvate kinase
insulin dephosphorylates pyruvate kinase (PK), which activates it
How does glucagon affect pyruvate kinase (PK)
- glucagon binding activates adenylate cyclase
- adenylate cyclase turns ATP into cAMP
- cAMP activates PKA
- PKA phosphorylates and inactivates PK
What are the non-hormonal regulators of glucokinase
high Km
What are the non hormonal regulators of PFK-1
activators
AMP
fructose-2,6-bisphosphate
Deactivators
ATP
What are the non hormonal regulators of PK
activators
fructose-1,6-bisphosphate
dephosphorylation
inactivators
phosphorylation
ATP
Alanine
What are the three enzymes of glycolysis that need to be bypassed in gluconeogenesis (only in liver)
- Glucokinase
- PFK-1
- PK
How is the bypass of glucokinase in the liver done
by glucose-6-phosphatase
how is the bypass of PFK-1 in gluconeogenesis done
by Fructose-1,6-bisphosphatase. But this enzyme is regulated too.
What is the process by which fructose-1,6-bisphosphatase is regulated so that it can bypass the PFK-1 reaction
fructose-1,6-bisphosphatase is inhibited by fructose-2,6-bisphosphate.
this is created by PFK-2, and it is eliminated (back into fructose-6-phosphate) by fructose-2,6-bisphosphatase
when fructose-2,6-bisphosphatase is active, converts the fructose-2,6-bisphosphate into fructose-6-phosphate.
this means lower levels of fructose-2,6-bisphosphate, which means the fructose-1,6-bisphosphatase is active, and bypasses the PFK-1 reaction
How is the bypass of the pyruvate kinase reaction done
- pyruvate that is normally converted into Acetyl-CoA and run through the Krebs cycle is instead converted into Oxaloacetate by Pyruvate carboxylase.
- Oxaloacetate is converted into Malate by MDH (malate dehydrogenase)
- Malate is shipped out of the mitochondria
- Malate is converted back into Oxaloacetate by MDH
- Oxaloacetate in converted back into PEP by PEPCK
Where does the bypass reaction of PK happen
first portion is in the mitochondria, then the second portion is in the cytosol
What are the enzymes that play in the PK bypass reaction
- Pyruvate carboxylase
- MDH
- MDH
- PEPCK (phosphoenolpyruvate carboxykinase)
What is the effect of insulin on gluconeogenesis, and how does it do that
it inhibits gluconeogenesis
- by dephosphorylating PK (activating PK)
- by deactivating fructose-2,6-bisphosphatase, increasing fructose-2,6-bisphosphate, which activates PFK-1, and inhibits fructose-1,6-phosphatase
What is the effect of glucagon on gluconeogenesis, and how does it do that
it activates gluconeogenesis
- by phosphorylating and deactivating PK
- by activating adenylate cyclase, which increases cAMP, which activate PKA, which phosphorylates fructose-2,6-bisphosphatase, which activates it, which lowers fructose-2,6-bisphosphate, which inhibits PFK-1 and activates fructose1,6-bisphosphatase
What is the effect on pyruvate carboxylase by insulin and glucagon (pyruvate carboxylase is used in the pyruvate kinase bypass reaction)
insulin and glucagon have no effect on pyruvate carboxylase
What is the effect on PEPCK (PEPcarboxykinase) by insulin and glucagon (PEPCK is used in the pyruvate kinase bypass reaction)
Insulin inhibits PEPCK
glucagon activates PEPCK
What is the affect of high levels of alanine on glycolysis/gluconeogenesis
high levels of alanine inhibit pyruvate kinase (increasing gluconeogenesis)
If no hormones regulate pyruvate carboxylase, then what does
Acetyl-CoA
how does Acetyl-CoA regulate pyruvate carboxylase
high levels of Acetyl-CoA activate pyruvate carboxylase (shows that there is enough energy in the liiver, so it can be used in a different way, glycogenesis, lipogenesis, or glucose shipped out to the body)
Why is it significant that the pathways of glycolysis and gluconeogenesis are reciprocally regulated (What activates one pathway deactivates the other)
to avoid a futile cycle
We know how to do gluconeogenesis from pyruvate right, what different things can be converted into pyruvate
- Lactate
- alanine
- cysteine
- glycine
- serine
- tryptophan
What happens once Lactate, alanine, cystein, glycine, serine, and tryptophan have been converted into pyruvate (in gluconeogenesis)
the pyruvate is converted into Oxaloacetate, then into malate, then shipped out of the _____, converted back into Oxaloacetate, then back into PEP
Some Amino acids aren’t converted into pyruvate, but into Oxaloacetate, which ones are they
Aspargine
Aspartate
Is glycerol a gluconeogenic substrate
yes
how does glycerol enter the gluconeogenic pathway
glycerol is converted into Glyceraldehyde-3-phosphate by glycerol kinase, then from glyceraldehyde-3-phosphate into dihydroxyacetone phosphate, and then from dihydrosyacetone into fructose-1,6-bisphosphate. and then up through gluconeogenesis
Can we get glucose from fatty acids
nope
Why can’t we get glucose from fatty acids
Beta-oxidation (breaking down of fatty acids) leads to Acetyl-CoA, when Acetyl-CoA goes through the citric cycle, 2 CO2’s leave, so you can’t use them to create more glucose. (no net gain of C)
Why can lipolysis increase glucose production if beta-oxidation doesn’t
becuase lipolysis is the breakdown of a triglyceride. triglycerides have glucogenic parts
what are the parts of a triglyceride
glyceride
fatty acids
which pars of a triglyceride are glucogenic
glyceride
If fatty acids can’t be turned into glucose, what do they become in lipolysis
Acetyl-CoA
What is the NET gain of ATP in glycolysis
2 ATP (2 Used, 4 made)
What is the NET gain of NADH in glycolysis
2 NADH
When using glycerol to make glucose, how many glycerol molecules are needed to make one glucose molecules
2
when using glycerol to make glucose, how many ATP are required to make a molecule of Glucose
2 (1 per glycerol molecule)
When using glycerol to make glucose, how many NADH are required to make a molecule of glucose
2 (1 per glycerol molecule)
Where does gluconeogenesis from glycerol occur
only in the liver
In starvation what is the first source of glucose
Amino Acids from the muscle
If Fatty acids can’t produce glucose, what good are they in starvation when we need energy
They can be a source of ketone bodies,
What is the initial substrate in the formation of ketone bodies
Acetyl-CoA
What is the good that comes from ketone bodies
they can be used like glucose (for energy)
When do we get anaerobic glycolysis
Anaerobic glycolysis occurs in the absence of oxygen, or when energy demand is high and immediate
What is the difference between aerobic and anaerobic glycolysis
aerobic glycolysis allows the NADH’s made in glycolysis to be used in the ETS-Ox Phos system to make more ATP.
Anaerobic glycolysis can’t use the NADH’s made in glycolysis, so the 2 ATP from glycolysis are the only ATP’s made
How many ATPs are made from aerobic glycolysis (not including the Aceyl-CoA going through the crebs cycle)
7
2 from glycoglysis
5 from the two NADHs made (2.5 ATP per NADH that goes through the ETC-Ox-phos system)
how many ATP are made from anaerobic glycolysis
2
if the NADH made in glycolysis can’t go to the ETS-Ox Phos system becuase of anaerobic conditions what happens to it
The NADH is used by lactate dehydrogenase to create lactate from pyruvate. and NAD+ results
What is the enzyme that makes lactate,
lactate dehydrogenase
When do we make lactate
in anaerobic conditions
What is the significance of Lactate dehydrogenase using NADH and leaving NAD+
the NAD+ can be used to continue glycolysis, so more ATP can be made
When do we have anaerobic glycolysis
- in RBCs (because they don’t have mitochondria)
- in vigorously working muscle (inadequate oxygen delivery)
- Blockage of blood flow
- in many tumors
What happens to the lactate that is created by lactate dehydrogenase in anaerobic conditions (usually from RBC’s and working muscle)
- it can be taken to resting skeletal muscle or the heart
- it can be taken to the liver
- it can be used by the very muscle that created it
What happens to the lactate that has been taken to resting skeletal muscle or heart
it is converted into pyruvate, then it goes through the krebs cycle and ETS-Ox phos
what happens to the lactate that has been taken to the liver
it is converted into pyruvate, then it goes through gluconeogenesis to produce glucose
what is the Cori cycle
the catabolism of glucose carbons to lactate in the peripheral tissue, then the anabolism of lactate back into glucose in the liver
