MCBG S17 Glycolysis Regulation

Question 1

What are the 2 important intermediates in glycolysis?

Answer 1

DHAP - dihydroxyacetone phophate

1,3-BPG

Question 2

Why is DHAP important?
Where is it important?
What are the enzymes and products in the pathway it’s important in?

Answer 2

Important in TAG and phospholipid synthesis
Liver and adipose
Converted by glycerol-3-phosphate dehydrogenase to glycerol phosphate
Glycerol phosphate will combine with FAs to form TAGs

Question 3

Lipid synthesis requires glycolysis.

True or false?

Answer 3

True.

Question 4

Why is 1,3-BPG important?

What is it converted to and by what enzyme?

Answer 4

• Converted from 1,3-BPG to 2,3-BPG.
• By enzyme bisphosphoglycerate mutase
• 2,3-BPG promotes tense state of haemoglobin and therefore is an important regulator of oxygen affinity of haemoglobin.

Question 5

Describe allosteric regulation of PFK - the key regulatory of glycolysis?

Answer 5

Regualted by ATP:AMP ratio

If high then inhibit and vice versa

Question 6

Describe hormonal regulation of PFK1.

Answer 6

Stimulated by insulin

Inhibited by glucagon

Question 7

Describe allosteric regulation of hexokinase.

Answer 7

Inhibited by G-6-P

Question 8

Describe hormonal regulation of PFK and pyruvate kinase.

Answer 8

high insulin:glucagon stimulate

Question 9

Describe metabolic regulation of glycerate-3-phophate dehydrogenase.

Answer 9

NADH:NAD+ ratio causes product inhibition of step 6 inhibiting glycolysis.

Question 10

NAD+ + NADH levels are constant in a cell.

True or false.

Answer 10

True

Question 11

Normally NAD+ is regenerated where?

Answer 11

Oxidative phosphorylation

Question 12

In what situations may NAD+ regeneration in stage 4 metabolism not be possible?

How can we regenerate NAD+ in these scenarios?

Answer 12

• RBCs no stage 3/4 metabolism
• Low Oxygen levels levels - stage 3/4 reduced.
• Lactate dehydrogenase LDH - produce Lactate

Question 13

Describe the reaction LDH undergoes.

What is reduced and oxidised?

Answer 13

NADH + H+ + Pyruvate -> Lactate + NAD+

Redox - pyruvate reduced, NAD+ oxidised.

Question 14

Why is Lactate normally metabolised by the liver and heart though the reverse reaction back to pyruvate?

How can the pathway in the liver be impaired?

Answer 14

Because liver and heart have sufficient O2 supply and therefore sufficient stage 3/4 metabolism to allow for NADH to be re-oxidised in oxidative phosphorylation.

Cirrhosis
Thiamine deficiency
Excessive alcohol consumption
Impaired enzyme deficiencies

Question 15

What is the concentration of lactate usually?

Answer 15

~1mM

Question 16

What does concentration of Lactate have to be to signal hyperlactemia?

Is this concentration below renal threshold?
Is there a change in the blood pH?

Answer 16

2-5mM
Yes
No

Question 17

What does the concentration of lactate have to be in order for lactic acidosis to occur?

Is this above the renal threshold?

What will happen to the Lactate?

Answer 17

more than 5mM

yes

Excreted in urine

Question 18

Describe the process of fructose metabolism.

Is ATP expended?

Answer 18

Fructose converted via fructose kinase to f-1-p.
F-1-P is cleaved by aldolase to glyceraldehyde and DHAP.
Triose kinase converts glyceraldehyde to G-3-P and DHAP converted to G-3-P by triose phosphate isomerase.
2 molecules of G-3-P made enter glycolysis.
ATP is expended - 2 molecules.

Question 19

What is essential fructouria?

What is its cause?

Clinically benign or harmful?

Answer 19

Fructose in urine

Deficiency in hepatic fructose kinase

Benign

Question 20

What is fructose intolerance caused by?

What does it result in?

How is it treated?

Answer 20

Caused by deficiency of aldolase

Meaning F-1-P accumulates in liver.
Leads to damage

Removal of fructose from diet.

Question 21

How is galactose metabolised?

Answer 21

Converted to galactose-1-phophate by galactose kinase.
Converted to glucose-1-phophate by uridyl transferase
G-1-P converted to G-6-P by phosphoglucomutase.
Enters glycolysis.

Question 22

Describe the process by which Galactose-1-P is converted to glycogen.

Answer 22

Galactose-1-P converted to UDP-galactose by UDP galactose epimerase.

UDP-galactose converted to UDP-glucose by UDP glucose 4-epimerase.

UDP glucose converted to glycogen via glycogen synthase.

Question 23

What is classic galactosaemia caused by?

What accumulates and what are the effects and clinical implications of this?

Answer 23

Caused by galactose-1-P uridyl transferase deficiency.

Galactose-1-P accumulates - hepatotoxic - liver fucntion is reduced
Bilirubin breakdown reduced - jaundiced

Question 24

What is another pathway galactose can enter?

Describe this pathway.

What are the clinical implications of this pathway?

Answer 24

Reduced to galactilol by aldolase reductase oxidising NADPH to NADP.

Galactilol accumulates in lens of eye causing cataracts.

Question 25

Why do reduced NADPH levels result in cataracts?

Answer 25

NAPPH usually keeps sulphydryl groups in their reduced forms Not forming disulfide bridges NADPH depletion means inappropriate disulphide bond and cross linking Precipitation of proteins in lens of eye.

Question 26

What are the 2 main functions of the pentose phosphate pathway? Where does it occur? Does it produce ATP?

Answer 26

Produce NADPH - Reducing power and maintain sulphydryl groups in reduced form. Produce 5C sugar ribose phosphate - needed for nucleic acid synthesis Cytoplasm No ATP

Question 27

What are the 2 main stages of the pentose phosphate pathway?

Answer 27

Oxidative decarboxylation of G-6-P to 5c sugar phophates reducing NADP+. Multistep rearrangement of glycolytic intermediates. - 3 5C sugars to 2 F-6-P and 1 G-3-P resented glycolysis.

Question 28

What can reduced NADPH levels lead to in RBCs?

Answer 28

Aggregated proteins called Heinz bodies result in haemolysis of RBC.