Biochem Week 3 - Glycogenolysis, Glycolysis, Gluconeogenosis, Cori Cycle, etc.

Question 1

Glycolyisis

What is the Function

Where tissues is it performed in?

Is it a cytosolic or mitochondrial process?

What are the inputs and outputs?

What are the regulatory enzymes/stemps and what modulates them?

Answer 1

Function: To degrade glucose for energy

Where (body): **LIVER, MUSCLE CELLS, **brain, kidney, RBCs, adipocytes

Where (cell): Cytosolic process

I_nputs/outputs:_ Glucose + 2 ATP –> 2 pyruvate + 4 ATP + 2NADH

Regulatory enzymes/steps and modulators:

1. ) Hexokinase (glucokinase in liver) - converts glucose into G-6-P. Modulated by G-6-P (or F-6-P in liver)
2. ) Phosphofurctokinase (PFK) - RATE LIMITING STEP - converts F-6-P into F-1,-6-BS. Inhibited by ATP (High energy) activated by AMP (low energy). Strong activation by F-2, 6-BS
3. ) Pyruvate Kinase - modulated by

Question 2

What is Hexokinase called in the Liver? How is it different?

What processes is it involved in?

Answer 2

Glucokinase

Indirectly -inhibited by F-6-P (NOT G-6-P like other hexokinases) to ensures that there is not a futile cycle between glycolyisis and gluconeogenesis w/o letting glycogen synthasis or degredation interfere.

Glycolysis and Gluconeogenesis

Question 3

What are most hexokinases allosterically inhibited by?

What tissues?

Why?

Does it make or use ATP?

Answer 3

G-6-P

Muscle, adipose brain, RBCs. _NOT LIVER. _

Slows down hexokinase activity of converting Glucose –> G-6-P so that you don’t have more G-6-P hanging around then can be used.

Question 4

What does Phosphofructokinase-1 (PFK-1) do?

Does it make or use ATP?

What activates it, what inhibits it?

What process is it involved in?

Answer 4

Converts F-6-P into F-1,6-BP.

It uses an ATP.

Activated by AMP and F-2,-6-BP. Inhibited by excess ATP.

Glycolysis

Question 5

What does Phosphofructokinase-2 (PFK-2) do?

When is it activated?

Where would you not likely see as PFK-2 and why?

What process is it involved in?

Answer 5

Converts F-6-P into F-2,6-BP

Activated if there is too much F-6-P compared to F-1,6-BP. F-2,6-BP further stimulates PFK-1 to get the conversion of F-6-P to F-1-6-BF to go faster.

Wouldn’t see it in the liver as much as other tissues since the liver is trying not to use glucose so that it can be saved for other tissues.

Glycolysis

Question 6

What is the rate limiting step in glycolysis?

Answer 6

PFK-1 converting F-6-P into F-2,6-BP

Question 7

What does Pyruvate Kinase do?

What is it activated/inhibited by?

What process is it involved in?

Answer 7

Converts PEP to Pyruvate

Activated by F-1,6-BP and PEP. Inhibited by acetyle CoA and ATP.

Glycolysis

Question 8

In the liver, how does glucagon and epinephrine affect pyruvate kinase and why?

Answer 8

Deactivates Pyruvate kinase by phosphorylating it.

Quick pathway: Glucagon + epinephrine signal through PKA-cAMP dependent kinase phophorylates and inactivates PK.

Question 9

If NADH is converted to NAD+, what kind of reaction is it (reduction or oxidation)?

Answer 9

Oxidation!

It loses an election.

Question 10

Generally what do kinases do?

What are some intermediates hat they use?

Answer 10

Phosphorylate another protein

NAD+/NADH

FADH/FADH2

Coenzyme A (eg. acetyl CoA)

Question 11

Generally, what do phosphatases do?

Answer 11

Dephosphoralyates another protein.

Question 12

Does the phosphorylation of pyruvate kinase activate or deactivate it?

Answer 12

Deactivates it.

This can be done in the liver through Glucagon and epinephrine.

Question 13

Generally, what do Dehydrogenases do?

Question 14

Where is GLUT 1 expressed?

Is it affected by insulin?

Answer 14

RBCs

Not affected by insulin.

Question 15

Where is GLUT2 expressed?

Is it affected by insulin?

Answer 15

Liver

Not affected by insulin.

Question 16

Where is GLUT4 expressed?

Is it affected by insulin?

Answer 16

Muscle cells and adipocytes.

YES! insulin causes it to be translocated to membrane.

Also, in skeletal muscle, contraction will cause it to be translocated to memebrane.

Question 17

Glycogenesis

What is the Function

Where tissues is it performed in?

Is it a cytosolic or mitochondrial process?

What are the inputs and outputs?

What are the regulatory enzymes/stemps and what modulates them?

Answer 17

_Function: _To build glycogen from glucose

Where (body): LIVER and muscle

Where (cell): Cytosolic process

Inputs/outputs: Glucose + ATP –> Glycogen

Major Regulatory enzymes/steps and modulators:

1. ) Hexokinase (glucokinase in liver) - converts glucose into G-6-P.
2. ) Glycogen Synthase - Converts UDP-Glucose to glycogen. Must be dephosphorilated to work. Insulin and G-6-P stimulates activity; glucagon and epinephrine decreases activity.

Question 18

Why does glycogen have branches?

Answer 18

Increases solubility.

Allows more than one site to be degraded at once.

Question 19

Glycogenolysis

What is the Function

Where tissues is it performed in?

Is it a cytosolic or mitochondrial process?

What are the inputs and outputs?

What are the regulatory enzymes/stemps and what modulates them?

Answer 19

_Function: _To degrade glycogen into glucose

Where (body): LIVER and muscle

Where (cell): Cytosolic process

Inputs/outputs: Glycogen –> G-6-P

Major Regulatory enzymes/steps and modulators:

1.) Glycogen Phosphorylase - converts glycogen to G-1-6 which then becomes G-6-P. Activated by phosphorylase kinase (low energy molecules and glucogon). Inhibited by insulin and high levels of G-6-P, ATP,

Question 20

What pathway is glycogen phosphorylase in?

What does it do?

Answer 20

Converts glycogen to G-1-6 which then becomes G-6-P.

Activated by phosphorylase kinase (low energy molecules and glucogon). Inhibited by insulin and high levels of G-6-P, ATP,

Question 21

After pyruvate is made in glycolysis, what can happen to it?

Answer 21

1) Is oxidized by pyruvate dehydrogenase in mitochondria to enter the Triboxilate Citric Acid (TCA) cycle for further oxidation all the way down to CO2 and NADH/FADH.
2. ) Reduced to lactate by lactate dehydrogenase (LDH) and transported to the liver (Cori Cycle)
3. ) Carboxylated (oxidation) to oxaloacetate in mitochondria for replenishment of TCA intermediates.

Question 22

What does the Pyruvate dehydrogenase (PDH) Complex do?

What does it need to work?

What is it inhibited by?

Answer 22

Simultaneously transports pyruvate into mitochondria while oxidizing and decarboxylating it into acetyl CoA.

Requires 5 cofactors: Thiamine, NAD+, FAD, CoA (All B vitamins), and Lipoate (Lipoic acid)

Inhibited by high energy signals (NADH, ATP, Acetyl CoA), stimulated by pyurvate and calcium.

Question 23

What happens when the PDH complex is overwhelmed or inactive?

Is pyruvate oxidized or reduced?

in what tissues does this happen?

Where does it occur in the cell?

Answer 23

If there is too much pyruvate building up, Lactate dehydrogenase (LDH) converts pyruvate into lactate.

Reduced, because NADH is oxidized to NAD+.

Non-hepatic cells.

Occurs in cytosol.

Question 24

Generally, what is the Cori Cycle?

What are some instances where it might occur?

Answer 24

A way for the liver to recycle pyruvate back into glucose in the event that there is a build up of pyruvate and it cannot be oxidized.

1. ) The TCA cycle and PDH of the muscle are satruated.
2. ) Not enough oxygen delivery (anarobic respiration)

3,) Few or no mitochondria around.

Question 25

in the LDH and Cori cycle, what is the point of converting pyruvate to lactate in the muscles if it is just going to be turned back into pyruvate in the liver?

Answer 25

Pyruvate is too polar of a molecule to make it through the cell membrane so it is reduced to lactate to travel back to the liver.

Question 26

Is the activity of LDH reversible?

Answer 26

Yes. it converts pyruvate to lactate in the muscle, and then back to pyruvate in the liver.

Question 27

What regulates the Cori Cycle?

How does it work?

Answer 27

The NADH ratio in both the skeletal muscle and the hepatocytes.

Not having enough NADH in the skeletal muscle keeps pyruvate from being reduced to lactate.

Not having enough NAD+ keeps the lactate from being oxidized to pyruvate.

Question 28

What happens when there is not eough NAD+ in liver to convert lactate back to pyruvate?

What would be the concequence?

Answer 28

Lactate stays in blood. Also the pyruvate can run in the wrong direction in the liver which can make the liver contribute to the lactic acid in the blood.

Lactic acidosis. BAD - occurs in bindge drinking alcohol.

Question 29

Gluconeogenesis

What is the Function

Where tissues is it performed in?

Is it a cytosolic or mitochondrial process?

What are the inputs and outputs?

What are the regulatory enzymes/stemps and what modulates them?

Answer 29

Function: To generate NEW glucose from amino acid skeletons, glycerol, and lactate. Would occur in starvation, low carb diet, diabetes.

_Where (body): _LIVER and a little in kidney

_Where (cell): _ Part mitochondria, part cytosol

Inputs/outputs: Pyurvate, lactate, glucogenic AA, glycerol

Major Regulatory enzymes/steps and modulators:

1. ) Pyruvate Carboxylase (mitochondria)
2. ) Phosphoenolphyruvate carboxykinase
3. ) Fructose Bisphosphatase

Question 30

What does pyruvate carboxylase do?

What pathway is it in?

Is it in the cytosol or the mitochondria?

Does it make or use ATP?

What is it activated by?

Answer 30

Adds a carbon group to pyruvate to make oxaloacetate (TCA cycle intermediate).

Gluconeogenesis

In mitochondria

Uses an ATP

Activated by build up of acetyl CoA (from FFA breakdown??)

Question 31

What is Malate dehydrogenase?

Why do we need it?

Answer 31

Catylzes the reversabe reduction of oxaloacetate to malate in the mitochondria so that it can be transported out of the cell to be oxidized back to oxaloacetate in the cytosol.

Its needed because oxaloacetate can’t pass the cell membrane, but malate has a membrane transporter.

Question 32

What is Phosphoenolpyruvate carboboxylase (PEP-CK)