Energy: Carbohydrates 2 Flashcards
2,3-bisphosphoglycerate (2,3-BPG)
(an important intermediate of glycolysis
- produced from 1,3-bisphosphoglycerate in RBC with the enzyme bisohosphoglycerate mutase
- is an important regulator of O2 affinity of Haemoglobin (reduces Hb affinity for oxygen by stabilising the tense form - more oxygen is released at the tissues)
Metabolic regulation of glycolysis
- high NADH concentration (low NAD+) = high energy signal
- results in product inhibition of step 6 (glyceraldehyde-6-phosphate to 1,3-BPG
- inhibition of glycolysis
Enzyme regulation
Enzymes catalysing irreversible steps (committing step) are potential sites of control
- ALLOSTERY (activator/inhibitor binds at a site other than the active site)
- COVALENT MODIFICATION (phosphorylation/dephosphorylation) phosphate is large and negatively charged - will affect the shape and therefore the properties of the protein
- PRODUCT INHIBITION (the accumulation of the product of a reaction inhibits its own production)
Oxidation/reduction step 6
- NAD+ linked - 2 moles of NADH produced per mole of glucose
- glycolysis needs NAD+
- total NAD+/NADH in cell is constant
- under aerobic conditions NAD+ is regenerated by reoxidation of NADH in stage 4 of metabolism
But: RBC have no stage 3/4 - stage 4 needs oxygen and supply of oxygen to muscle is often reduced - e.g. during exercise
NEED TO REGENERATE NAD+ BY ANOTHER METHOD - (LDH) Lactate Dehydrogenase
Lactate Dehydrogenase reaction
NADH + H+ NAD+ + lactate
- lactate is produced by RBC and skeletal muscle
- released into the blood (would acidify the cell otherwise)
- normally metabolised by the liver and heart (via LDH)
Tissues that work anaerobically (e.g. skeletal muscle during exercise) with tissues that work aerobically (e.g. the liver and heart)
Lactate utilisation
Via pyruvate (LDH enzyme)
NAD+ + lactate –> NADH + H+ + pyruvate
Heart muscle
lactate –> CO2
Liver
lactate –> glucose (by gluconeogenesis)
this is impaired in liver disease, B1 (thiamine) and enzyme deficiency, on alcohol consumption
Lactate production
Produced from glucose (and alanine) via pyruvate
Without major exercise (40-50g/24hrs)
Strenuous exercise/hearty eating (30g/5mins)
- plasma levels increase x10 in 2-5mins
- return to normal by 90mins
Pathological situations e.g. shock or congestive heart disease
Plasma lactate concentrations
(normally constant
Hyperlactaemia
- 2-5mM
- below renal threshold - no lactate in urine
- no change in blood pH (due to the buffering capacity)
Lactic Acidosis
- >5mM (can be achieved with intense exercise)
- a over renal threshold
- blood pH is lowered
Metabolism of fructose and galactose
All sugars can lead into glycolysis
All sugars are activated by ATP
GALACTOSE
- converted to G-1-P then G-6-P which enters glycolysis
FRUCTOSE
- converted to G-3-P which then enters glycolysis
Fructose metabolism
in the liver
Fructose is activated by ATP and converted to Fructose-1-P by fructokinase.
Fructose-1-P is converted to 2-glyceraldehyde-3-P (which enters glycolysis) by aldolase.
- fructokinase missing (fructose in urine, no clinical signs)
- aldolase missing (fructose-1-P accumulates in the liver causing liver damage - fructose has to be removed from the diet)
Galactose metabolism
in the liver
Lactose = galactose + glucose
Galactose is activated by ATP and converted to galactose-1-P by galactokinase
Galactose-1-P is swapped for glucose (UDP-galactose –> UDP-glucose) with UDP-galactose 4’epimerase and then converted to glucose-1-P (which enters glycolysis) by the enzyme galactose-1-P uridyl transferase
Galactosaemia
Galactokinase deficient is rare (galactose accumulates in the blood and is excreted in the urine)
Transferase deficiency is more common (galactose and galactose-1-P accumulate which causes problems)
- galactose enters other pathways: galactose is reduced by NADPH to galactitol via aldose reductase
- this depletes the level of NADPH - causes structure damage in the lens of the eye and results in cataracts
- causes inappropriate disulphide bond formation, loss of structural and functional integrity of some proteins - they precipitate causing cataracts
- accumulation of galactose-1-P affects the liver, kidney and brain
- treatment is to remove lactose from the diet
The pentose phosphate pathway
activated when energy levels are high
Important pathway in the production of NADPH
Cytoplasmic
- oxidative decarboxylation (irreversible) - produced 5C sugar phosphates
- rearrangement into glycogen intermediates
- no ATP production
- controlled by NADP+/NADPH ratio at G6P dehydrogenase
Produces NADPH in the cytoplasm
- a Biosynthetic reducing power (e.g. for lipid synthesis - therefore high levels in the liver and adipose tissue)
- maintains free -SH group on certain proteins (prevents the formation of inappropriate disulphide bonds by oxidation)
Produces 5C sugar for nucleotides (so high activity in dividing tissues e.g. bone marrow)
Glucose 6-phosphate dehydrogenase deficiency
G6P cannot be used to regenerate NADPH (less 5C sugars are produced) - the structural integrity of many proteins is compromised
In RBC a reduction in NADPH leads to:
- inappropriate disulphide bond formation
- aggregated proteins - Heinz bodies formation
- haemolysis
- ANAEMIA as production can not keep up with the destruction of RBC
Glycerol Phosphate (an important intermediate of glycolysis)
Dihydroxyacetone phosphate (DHAP) is reduced by NADH by the enzyme glycerol-3-phosphate dehydrogenase to produce glycerol phosphate
- important to triglyceride and phospholipid biosynthesis
- produced from DHAP in adipose tissue and liver
- LIPID SYNTHESIS IN THE LIVER REQUIRES GLYCOLYSIS for the glycerol-3-phosphate
