2.2 Energy Production - Carbohydrate Metabolism

Question 1

Explain why lactic acid (lactate) production is important in anaerobic glycolysis.

Answer 1

Needed to regenerate NAD+ by an alternative pathway.

For example due to insufficient oxygen for oxidative phosphorylation.

Lactate dehydrogenase:
pyruvate <–> lactate (NADH + H+ –> NAD+)

Reversible reaction.

ALSO: pyruvate may be used in gluconeogenesis to produce glucose in the liver. May be impaired by vitamin/enzyme deficiencies.

Question 2

Explain how the blood concentration of lactate is controlled.

Answer 2

Normal lactate <1mM.
- normally constant, with production, utilisation (liver/heart/muscle) and disposal by the kidneys.

2-5mM:
- hyperlactaemia.
- no pH change due to buffering.

5mM+:
- lactic acidosis
- pH drops (outside 7.35-7.45 normal range)
- critically unwell.

Question 3

Explain how sugars other than glucose are metabolised.

Answer 3

Fructose:
- metabolised in liver.
- fructose –> G-3-P –> pyruvate.
- essential fructosuria (fructokinase missing) –> fructose in urine.
- fructose intolerance (aldolase missing) –> fructose 1 phosphate accumalates in liver, causing depletion of phosphate ions, so liver damage as unable to make ATP.

Galactose:
1. galactokinase (galactose –> galactose-1-phophate)
2. Galactose-1-phophate uridyl transferase (GALT) (galactose-1-phosphate –> glucose-1-phosphate + UDP-galactose)
3. UDP-galactose 4’-epimerase (UDP-galactose –> UDP-glucose)

Question 4

Explain the biochemical basis of the clinical conditions of galactosaemia.

Answer 4

unable to digest galactose.. e.g. lactose in milk.

caused by the absence of:

• galactokinase, rare. Galactose accumalates.
• galactose-1-phosphate uridyl transferase (GALT), common. Galactose & galactose-1-phosphate accumalates.

Leads to galactose entering other pathways:
- galactose –> (aldose reductase) galactitol
- depletes lens of NADPH, leading to cateracts.

Question 5

Explain why the pentose phosphate pathway is an important metabolic pathway in some tissues.

Answer 5

Glucose-6-phosphate dehydrogenase enzyme.

Source of NADPH - needed to provide reducing power for biosynthesis, maintain GSH levels and detoxification reactions.

Produces 5 carbon ribose sugar, which is needed to synthesise nucleotides, DNA and RNA.

Produces CO2. No ATP.

Question 6

Describe the clinical condition of glucose 6-phosphate dehydrogenase deficiency and explain the biochemical basis of the signs and symptoms.

Answer 6

1. Deficiency in NADPH.
2. Less -SH groups, more -S.
3. Disulphide bonds form between -S groups.
4. Proteins aggregate called heinz bodies.
5. Haemolysis (RBC destroyed) –> leads to conditions like anaemia.

Question 7

Describe the control of glycolysis.

Answer 7

Stage 3 of glycolysis.

Phosphofructokinase converts fructose-6-phophate to fructose-1,6-bisphosphate using a molecule of ATP.

Enzyme inhibited by high ATP or high citrate.
Stimulated by high AMP or fructose-2,6-bisphophate (low energy signal & end product inhibition).

Occurs at allosteric site.

Stimulated by insulin –> causes glucose to be used up.
Inhibited by glucagon –> reduces glucose used up.

ALSO:
- Stage 1: hexokinase (NOT glucokinase in liver) inhibited by glucose-6-phosphate.
- Stage 10: pyruvate kinase stimulated by high insulin:low glucagon.