Glycolysis and Gluconeogenesis

Question 1

Absorption of dietary sugars/carbohydrates from the lumen of the gutinto blood is only as a…

Answer 1

monosaccharide

Question 2

Lactose is broken down to…

Answer 2

galactose and glucose

Question 3

Starch is broken down to

Answer 3

glucose

Question 4

Sucrose is broken down to

Answer 4

glucose and fructose

Question 5

Galactose is converted to what in the liver?

Answer 5

glucose

Question 6

Fructose can be converted to what in liver?

Answer 6

Glucose and F-6-P

Question 7

Describe GLUT 1 & 3

Answer 7

low Km (hi affinity); unregulated activity                   - basal transport/uptake even when blood [glucose] low                     
- “constant need”
RBC, brain, kidney

Question 8

Describe GLUT 4

Answer 8

low Km (hi affinity), regulated by insulin
mechanism: transporters moved to cell membrane
active only in fed state
muscle, adipose
muscle contraction (exercise) also activates GLUT 4

Question 9

Describe GLUT 2

Answer 9

high Km (low affinity), unregulated
active mostly when blood [glucose] high (fed state)
found in cells that regulate blood [glucose] levels
pancreatic b-islet cells, liver

Question 10

Recheck: What are insulin’s functions?

Answer 10

• master hormone that ”drives the recovery process”
  
  • promotes uptake of glucose by muscle (& adipose)
  • stimulates glycogenesis in muscle & liver
  • stimulates protein synthesis in muscle

Note: Muscle is sensitized to insulin during exercise & for at least 2-4 hrs after exercise

Amino acids also stimulate insulin release by b-islet cells
– effect is synergistic with insulin

Question 11

What are the enzymes required to prime glucose for metabolism?

Answer 11

Hexokinase/Glucokinase

Question 12

What is the reaction for glucose once it gets into the cell?

Answer 12

ATP + glucose yields G-6-P + ADP (glucose was phosphorylated). This phosphorylation traps glucose inside the cells and enzymes pull it into the cell

Question 13

What is the function of hexokinase?

Answer 13

It is found in most tissues
Low Km (~0.1 mM; hi affinity); end product inhibited by glucose-6-P
Glucose phosphorylated even when blood [glucose] low
Glucose uptake limited by glycolysis

Question 14

Where is glucokinase found and what is its function?

Answer 14

Found in the liver and beta cells of pancreas

High Km (7.6 mM; low affinity); not inhibited by glucose-6-P
Glucose phosphorylated only when blood [glucose] high
High capacity - large quantities of glucose can be taken up
Glucose phosphorylation varies linearly with blood [glucose]

Question 15

What is glycolysis and what are the steps?

Answer 15

Glycosis is partial oxidation of G-6-P to pyruvate in the cytosol

Glu comes into cell and hexokinase phosphorates it and activates it for metabolism. G-6-P is major metabolic intermediate. 6 C of G-6-P end up being 2 3-C pyruvate. In some cases we will park pyruavte as lactate.

Question 16

What are the 4 steps to glycolysis?

Answer 16

Stage 1: E Investment: Glucokinase/Hexokinase rxn, 2 phosphate groups are put onto the end of the glucose molecule (2 ATP are converted to 2 ADP) The end product is Fruc-1,6-bp. (This is the activate sugar)

Stage 2: Sugar splitting. The Fruc 1,6 bp is cut into two activated sugars.

Stage 3: Oxidation-reduction. Get E out of the two molecules, a pair of energetic electrons and we put two more phosphate groups on each of the 3-C molecules.

Ste E present in the diphosphorylated sugards to make 4 atp. We end up with 2 3 C partially oxidized pyruvate molecules.

Question 17

What is the input and final products of glycolysis?

Answer 17

6 C Glucose in 2 x 3 C Pyr out
2 NADH: out*
*We must regenerate NAD+ from NADH:
2 ATP in 4 made 2 ATP out

Question 18

What is the major control point in glycolysis?

Answer 18

PFK. This tells us that we are going to go along with glycolysis and says yes we are going to make Fru 1,6, bp.

It is inhibited by: energy rich signals (ATP, NAHD:, citrate)

It is activated by Fructose-2,6 bp.

Question 19

In aerobic (oxygen is present) environment what happens to pyruvate

Answer 19

It goes into the mitochondria to be a part of the Krebs cycle and ATP is made

Question 20

In anaerobic environment what happens to pyruvate?

Answer 20

The 2 NADH: have electrons taken and they are put on the pyruvate to make lactate and NAD is regenerate. Gives us 2 ATP, 0 NADH, 2 lactate.

Question 21

What is the synthesis of PFK controlled by?

Answer 21

Activated by fructose 2, 6, bis-P which amplifies glycolysis.

Hormone signals. In liver and adipose insulin causes an increase in PFK synthesis.

In muscle, epinephrine increases the synthesis of PFK.

Question 22

What enzyme controls gluconeogenesis?

Answer 22

fructose-1,6-bis-phophatase. This decrease synthesis of PFK because this is trying to build up glucose stores not break them down.

Question 23

What is pyruvate kinase?

Answer 23

The enzyme that makes ATP in glycolysis

Question 24

When would you want to have a lot of glycolysis going on?

Answer 24

RBC need it all the time, O2 limiting activities, many tumor cells would want it.

Question 25

What occurs during amplified glycolysis?

Answer 25

Inhibitors of glycolysis (ATP and citrate) are low.
Glycolysis also amplified by conditions that increase fructose 2,6-bis-P levels

When exercising: ATP & citrate levels low – hi energy demand
Fructose-2,6-bis-Pi levels high

All muscle glycogen must go through glycolysis to make ATP

Question 26

What are the issues in regenerating cytosolic NAD+ from NADH:?

Answer 26

Issue 1: Glycolysis produces NADH:
NADH: (energy rich substance) inhibits glycolysis (PFK & pyruvate kinase)
But more importantly the shortage of NAD+ itself slows/stops glycolysis

Issue 2: Get the NADH: inside mitochondria good for making ATP
- PROBLEM: but NADH: doesn’t cross mitochondrial membrane

Question 27

How do we get rid of cytosolic NADH: (regenerate NAD+) under anaerobic conditions?

Answer 27

Under these conditions (rbc and strenously exercising muscle)
Take 2 elec from NADH: to reduce pyruvate to lactate. Reduce ketone to alcohol. Lactate carrying two electron is reduced pyruvate and then we do that we regenerate nad we can run another glu through glycolysis to make 2 more ATP. Instead of pyruvate you can oxidize to make more energy you get lactate.

Question 28

What is lactate dehydrogenase?

Answer 28

The enzymes that catalyzes the reversable reaction between pyruvate and lactate and between NADH: and NAD. This enzyme is found in all tissues. This also regenerates cytosolic NAD+. This conversion between pyruvate and lactate is freely reversable and driven by mass action. If there is a lot of NAD present and a lot of lactatethe reaction will shift to the left and more NADH: and more pyruvate will be made. If there is a lot of pyruvate and NADH: present we are going to shift to the right and more lactate and NAD+ will be made.

Question 29

How do we get rid of the lactate?

Answer 29

The Cori Cycle. Think in the rbc ANAEROBIC glycolysis always occurs and glucose is converted to pyruvate. LDH converts pyruvate further to lactate. The lactate leaves the rbc to the liver and the liver (losts of NAD+ and O2) LDH oxidizes lactate back to pyruvate. In the liver that pyr could be used in Gluconeogenesis. The glu can go back into the blood.

Question 30

How do we get rid of cytosolic NADH: (regenerate NAD+) under aerobic conditions? (Which is most of the tissues most of the time)

Answer 30

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