Energy Production-carbs 2

Question 1

What are the functions of glycolysis?

Answer 1

Oxidisation of glucose
NADH production (2 per glucose)
Synthesis of ATP from ADP
Produce C6 and C3 intermediates

Question 2

What are the features of glycolysis?

Answer 2

Central athwart of all CHO catabolism
Occurs in all tissues cytoplasm
Exergonic and oxidative
No loss of CO2
Only pathway that can operate anaerobically (with LDH)
Irreversible

Question 3

Why is Glycerol Phosphate an important intermediate in glycolysis?

Answer 3

Key in triglyceride and phospholipid synthesis
Lipid synth in adipose tissue requires glycolysis
It’s produced from DHAP in adipose and liver

Question 4

Describe the role and location of 2,3-Bisphosphoglycerate (a key intermediate in glycolysis).

Answer 4

It’s produced in RBC’s and is present at same molar concentration as heamoglobin.
It’s a regulator of heamoglobin O2 affinity (letting O2 unload at tissues)

Question 5

Why is NAD needed in glycolysis? And where does it come from in metabolism?

Answer 5

2 moles of NADH are produced per mole of glucose in glycolysis
Therefore pathway requires NAD
So glycolysis would stop when all NAD is converted to NADH

NAD is normally regenerated from NADH in stage 4 of metabolism

Question 6

What happens if no NADH is regenerated and why might this happen?

Answer 6

RBC’s don’t perform the 3rd or 4th stage of metabolism

Stage 4 also requires an O2 supply, this is often reduced in the muscles an gut so another form of registration must begin-anaerobic

This uses Lactate Dehydrogenase

Question 7

How is lactate produced and how much is produced?

Answer 7

It’s produced from glucose via pyruvate

At rest- 40-50g/24hours (RBCs, skin, brain, muscle, GI)

At exercise (inc eating)-30g/5mins

Pathological situations increase it-shock + congestive heart disease

Question 8

Describe how the lactate dehydrogenase reaction regenerates NAD.

Answer 8

NADH+H+pyruvate = NAD + lactate ( in low O2 situations this occurs)

The NAD and lactate then travel via the blood to cells with a rich O2 supply (ie heart or liver) to be used in stage 4 of glycolysis (as below)
NAD+lactate = NADH + H + pyruvate

The heart and liver are usually O2 rich so cant run out of NAD for stage 4 they therefore receive it from these O2 poor cells

Question 9

Why might the regeneration of NAD-NADH in the liver be impaired?

Answer 9

May be impaired by 
Liver disease
The vitamin deficiency of Thiamine
Alcohol turns NAD to NADH meaning the lactate is not deoxidised
Enzyme deficiencies

Question 10

What is the normal plasma lactate concentration?

Answer 10

Normally rests under 1 mM

Question 11

Describe Hyperlactaemia and when it occurs.

Answer 11

A plasma lactate conc of 2-5mM
Still below the renal threshold
No change in blood pH (within buffering capacity)

Question 12

Describe lactic acidosis and when it may occur.

Answer 12

Plasma lactate conc of above 5mM
Above the renal threshold
Lowered blood pH (outside buffering capacity)
A critical marker in an acutely unwell patient

Question 13

What 2 other sugars can the body metabolise?

Answer 13

Fructose and Galactose

Question 14

How are these other sugars (not glucose) metabolised?

Answer 14

They enter glycolysis after several other stages each.

Question 15

Name 2 key enzymes in fructose metabolism

Answer 15

Fructokinase and Aldolase

Question 16

Name 2 enzyme related issues that may occur in the metabolism of fructose and explain them.

Answer 16

1) Essentail Fructosuria- fructokinase enzyme missing = fructose present in urine, no damage caused, no treatment
2) Fructose Intolerance- Aldolase missing= fructose_1_P accumulates in the liver causing damages, treat by removing fructose from diet

Question 17

List 3 enzymes key for galactose metabolism.

Answer 17

Galactokinase
UDL-galactose epimerase
Uridyl transferase

Question 18

What are the roles of Galactokinase and Gallactose_1_P uricyl transferase in galactose metabolism?

Answer 18

Galactokinase uses 1 ATP to convert galactose to Galacoe_1_P.

Galactose_1-p uridyl transferase and UDP galactose epimerase, swaps UDP_glucose to UDP_galactose meaning Galactose_1_P is switched to glucose_1_P which can enter glycolysis.

Question 19

What is glactosaemia and what do the 2 types cause (accumulation wise)?

Answer 19

Unable to utilise glucose due to an enzyme deficiency.
If galactokinase deficiency (rare) then galactose accumulates

If transferase deficiency (common) then galactose and galactose_1_P accumulate

Question 20

What does a galactokinase deficiency cause?

Answer 20

Galactose accumulates in tissues.
As it cant enter glycolysis it enters other pathways

Aldose reductase enzyme uses NADPH to convert galactose to galactitiol and NADP+.
This deplete NADPH store which causes structural damage to protiens eg those in the eye lens (cataracts)

Treatment = no lactose in diet

Question 21

What does a transferase deficiency cause (in galactosaemia)

Answer 21

Galactose and galactose_1_P accumulate in tissues

Galactose uses up NADPH stores to make glactitol (using aldose reductase) causing issues with protein structures esp in eye lens

Galactose_1-p damages the liver, kidney and brain.

Treatment=no lactose in diet

Question 22

How do low NADPH levels caused by galactosaemia affect proteins?

Answer 22

Depleted NADPH levels prevent maintenance of free sulphydryl groups on protiens, leadin to inappropriate disulphides bond formation. This causes loss of structural and functional integrity of protiens that depend on free -SH groups.
Eg, in eye lens

Question 23

What is the pentose phosphate pathway?

Answer 23

A branch off of glycolysis.
G6PDH feeds a 6C molecule out of glycolysis into this pathway.
It expels CO2 and creates NADPH.
The Ribose-5-P product can either feed back into a sugar used in glycolysis or be used for nucleotides, DNA, RNA or coenzyme synth.

Question 24

What is NADPH used for?

Answer 24

Needed for fatty acid biosynthesis
Steroid biosynthesis
GSH regeneration

Question 25

Name the two stages in the pentose phosphate pathway.

Answer 25

1) oxidative decarboxylation (Glucose-6-P to C5 sugar and CO2 as NADP turns to NADPH)
2) rearrange the to glycolytic intermediates (multistep)

Question 26

What is the pentose phosphate pathway controlled by?

Answer 26

The NADP/NADPH ratio at G6P dehydrogenase

Question 27

What are the main functions f the pentose phosphate pathway?

Answer 27

Produce NADPH in cytoplasm (for biosynthetic reducing power and maintain free SH groups on proteins)

Produce C5 sugars for nucleotides needed in nucleic acid synthesis

Therefore high activity in dividing tissue (bone marrow etc)

Question 28

What happens if a person has a Glucose-6-Phosphate dehydrogenase (G6PDH) deficiency?

Answer 28

In RBCs low levels of NADPH, leads to formation of disulphide bonds, formation of aggregate proteins called Heinz bodies (look like baked beans), this leads to haemolytsis. In turn causes anaemia.

ESP effects eye lens