Energy Production: Carbohydrate 2

Question 1

What are some important intermediates in glycolysis?

Answer 1

Glycerol phosphate which lays the foundation for biosynthesis for fats.
2,3-biphosphoglycerate which is produced in red blood cells and is an important regulator of haemoglobin O2 affinity. An increased level of 2,3-biphosphoglycerate decreases the affinity for O2 and promotes release.

Question 2

Why is glycerol phosphate an important intermediate of glycolysis?

Answer 2

DHAP goes to glycerol phosphate with the oxidation of NADH.

Glycerol phosphate is important in synthesis of triglycerides and phospholipids

Question 3

Where is DHAP converted into glycerol phosphate?

Answer 3

In adipose tissue and in the liver. This means that lipid synthesis in liver requires glycolysis.

Question 4

What happens if all NAD+ is used up in glycolysis?

Answer 4

It stops because no more NADH can be produced.

Question 5

Where does NAD+ regenerate then?

Answer 5

It is converted from NADH in stage 4 of metabolism (electron transport chain).

Question 6

Why is this a problem in red blood cells?

Answer 6

Because of the red blood cells not having any mitochondria RBCs have no stage 3 and 4 and NAD+ is no regenerated by stage 4. Therefore NAD+ needs to be regenerated via some other route.

Question 7

What other route of NAD+ regeneration do RBCs use?

Answer 7

Via lactate production. Lactate dehydrogenase also called LDH is used:
NADH+H+ + pyruvate -> NAD+ and lactate

Question 8

Where is lactate produced?

Answer 8

In RBCs and skeletal muscle (skin, brain and GI)

Question 9

Where can you find lactate?

Answer 9

It is released into the blood.

Question 10

Where is lactate metabolised?

Answer 10

Usually by the liver and heart but also kidneys.

Question 11

Why would lactate be produced from pyruvate in skeletal muscle instead of pyruvate going into acetyl CoA and then TCA cycle and electron transport chain?

Answer 11

Due to a lack of oxygen. Pyruvate is then converted into NAD+ and lactate so NAD+ can be used again in glycolysis.

Question 12

Why is lactate metabolised in the liver and heart?

Answer 12

Heart as a use for energy.
Liver to form pyruvate again and there make more glucose from gluconeogenesis to transport it to the tissue again and use it for glycolysis.

Question 13

What is an elevated level of plasma lactate concentration called?

Answer 13

Hyperlactaemia. This is at 2-5mM. There is no change in blood pH at this rate.
Lactic acidosis is an even more elevated level of concentration above 5mM. This is above the renal threshold so lactate levels stack up. This causes the blood pH to be lowered. This can be very troublesome as a lower pH means enzymes do not work properly.

Question 14

Glucose is turned into G-6-P then G-3-P and then Pyruvate. Where does fructose, galactose, glycogen and lactate play part in that pathway?

Answer 14

Fructose is directly turned into G-3-P.
Galactose is first turned into G-1-P and then into G-6-P.
Glycogen is first turned into G-1-P and then into G-6-P.
Lactate is turned into Pyruvate.

Question 15

Briefly outline the pathway of Fructose into G-3-P.

Answer 15

Fructose turns into fructose-1-P by fructokinase. Aldolase then converts fructose-1-P to glyceraldehyde and DHAP which are then converted into G-3-P.

Question 16

How is fructose metabolism of clinical importance?

Answer 16

Essential fructosuria:
Fructokinase is missing.
Fructose intolerance:
Aldolase is missing.

Question 17

What are some side effects of essential fructosuria?

Answer 17

The only side effect is fructose in the urine. Because fructokinase is missing fructose never undergoes it reaction to enter glycolysis. It just exits the body. There are no clinical signs.

Question 18

What are some side effects of fructose intolerance?

Answer 18

This is a bit more serious because fructose has already started undergo the reaction to enter glycolysis. The fructokinase step is an irreversible step so there is now a build up of fructose-1-P in the liver. This can lead to liver damage.

Question 19

Briefly outline the pathway of galactose into glucose-1-P.

Answer 19

Lactose is broken down into glucose and galactose. Galactose is then via galactosekinase converted into Galactose-1-P. Uridyl transferase then converts it into glucose-1-P.

Question 20

There is another pathway for galactose than glucose-1-P. Which?

Answer 20

Galactose-1-P can turn into UDP-Galactose then UDP-Glucose and finally glycogen.
Galactose-1-P turns into UDP-galactose via UDP-galactose epimerase.

Question 21

Which of these enzymes can cause galactosaemia?

Answer 21

Any of the three.
Galactokinase
Uridyl transferase
UDP-galacto epimerase

Question 22

What is galactosaemia?

Answer 22

An inability to utilise galactose.
In galactokinase deficiency galactose will acculumulate
In transferase deficiency galactose and galactose-1-P will accumulate.

Question 23

Why is galactosaemia a problem?

Answer 23

The accumulation of galactose means that it will enter another pathway. This pathway is that galactose turns into galactitol via aldose reductase and the oxidation of NADPH to NADP+.

Question 24

What are the consequences of galactose being converted into galactitol?

Answer 24

NADPH is used up which should be used for biosynthesis. The release of the H+ also causes inappropriate disulphide bond formation. This causes loss of structural and functional integrity of some proteins that depend on free -SH groups like the lens of the eye.
This causes cataracts.

Question 25

Why is the elevated level of galactose-1-P a problem?

Answer 25

Because it is toxic in too high levels for the liver, kidney and brain.

Question 26

How can galactosaemia be treated?

Answer 26

By a lactose free diet.

Question 27

Glucose-6-P can go into yet another pathway. Which and why?

Answer 27

If there is plenty of glucose available glucose-6-P can go into pentose phosphate pathway. Here NADPH is formed for biosynthesis and Ribose-5-P that is required for:
Nucleotides
DNA
RNA
Coenzymes.
If it is not used for example nucleotide synthesis it can be fed into glycolysis again.

Question 28

What are the functions of the pentose phosphate pathway?

Answer 28

Production of NADPH for biosynthesis and maintenance of free -SH groups on certain proteins.
Production of Ribose-5-P for production of nucleotides etc.

Question 29

Where can pentose phosphate activity be found then?

Answer 29

In liver and adipose tissue due to the NADPH.

In the bone marrow (dividing tissue) due to the nucleotides.

Question 30

What happens if there is a deficiency of Glucose 6-phosphate dehydrogenase?

Answer 30

NADP+ can’t turn into NADPH, this causes the free -SH to not be present where they need to be, disulphide bonds are instead formed. Same problem as in galactosaemia because of this.
The production of Ribose-5-P won’t work properly this means that the bone marrow won’t work properly.
This causes red blood cell breakdown as well called haemolytic crisis where there is a rapid breakdown.

Question 31

So why is the pentose phosphate pathway important?

Answer 31

Due to the source of NADPH and taking away NADP+. Promotes biosynthesis and prevents formation of disulphide bonds.
Produces C5-sugar riboses that are important for synthesis of nucleotides and DNA and RNA for bone marrow and further on RBCs.
The enzyme used is Glucose-6-phopshate dehydrogenase.