Leyland 5 Catabolism stage 2 Flashcards
Glycolysis
- Central pathway of sugar metabolism
- Present in all cell types
- Takes place in the cytoplasm
Glycolysis
Overall reaction:
glucose + 2 Pi + 2 ADP + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Stage 1
- Input of some energy
* ATP used to phosphorylate intermediates
Stage 2
- C6 converted to 2 x C3
- ATP produced
- NADH produced
Aldolase
4
• doubly phosphorylated C6 sugar is converted into 2 x monophosphorylated sugars
Fructose 1,6 bisphosphate -> glyceraldeyde 3-phosphate + dihydroxyacetone phosphate
net yield
2x ATP per molecule of glucose converted to pyruvate.
Glyceraldehyde 3-phosphate dehydrogenase
• Generation of NADH
glyceraldyhde 3-phosphate + Pi -> 1,3, Bisphosphoglycerate
Phosphoglycerate kinase
- Generation of ATP
- Substrate-level phosphorylation
1,3, Bisphosphoglycerate -> 3-phosphoglycerate
Substrate level phosphorylation
Direct formation of ATP by transfer of phosphate group from 1,3 BPG to ADP
Summary of glycolysis
• Glucose oxidised to pyruvate
• C6 and C3 cmpds only; no loss of CO2
• Generates :
2 ATP (net)
2 NADH
• Overall exergonic (-ve DG)
• Irreversible pathway
glucose + 2 Pi + 2 ADP + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2 H+Glycolysis under aerobic conditions
- Pyruvate further oxidised in citric acid cycle
- NADH used to form ATP on oxidative phosphorylation
- NAD+ regenerated to allow glycolysis to continue
Stage III under aerobic conditions
- Stage III of catabolism does not occur
- NADH would not be oxidised
- Glycolysis stops due to lack of NAD+
- No ATP produced
yeast and some microorganisms:
Conversion of pyruvate to ethanol allows the oxidation of NADH to NAD
In mammals:
• when the supply of oxygen is inadequate
Pyruvate + lactate dehydrogenase -> Lactate
(eg skeletal muscle during rigorous exercise)
• in cells without mitochondria (eg red blood cells)
Regulation of Metabolism
Flux through metabolic pathways needs to be regulated in response to the demands of the cell.
In metabolic pathways, enzymes catalyzing essentially irreversible steps are potential sites of control.
Some enzymes can be regulated by :
• allostery (activator/inhibitor binds at ‘other’ site)
• covalent modification (phosphorylation/dephosphorylation)
Glycolysis: Key enzymes:
Hexokinase
- Phosphofructokinase
- Pyruvate kinase
Hexokinase (HK)
- phosphorylates glucose
- ATP consumed
- traps glucose inside the cell
Glucose -> glucose -6-phosphate
Phosphofructokinase (PFK)
- phosphorylates fructose 6-phosphate
- ATP consumed
phosphorylates fructose 6-phosphate -> fructose 1,6-bisphosphate
Pyruvate kinase
• Generation of ATP
• Substrate-level phosphorylation
phosphoenolpyruate -> pyruvate
Catabolism of other monosaccharides
All require activation: addition of phosphate, addition of UDP
2. Most sugar metabolism occurs in the liver
Fructose metabolism
Fructose (+ fructokinase)
-> fructose 1-phosphate ( + fructose 1-phosphate aldolase) -> glyceraldehyde + didroxyacetone phosphate (+triose kinase) -> glyceraldehyde 3-phosphate
fructosuria
Genetic deficiency of fructokinase causes fructosuria
Hereditary fructose intolerance is a severe condtion caused by lack of aldolase B
Galactose metabolism
galactose + atp -> glucose 1 - phosphate + ADP + H+
galactosaemia
Non-classical :Cataract formation
Classical: Abnormal mental development
The pentose phosphate pathway (PPP)
Catabolism of sugars – 5C sugar - phosphates
Cytosolic
Important in liver, RBC, adipose tissue
The pentose phosphate pathway (PPP)
Phase I Oxidative
- Irreversible
* Produces NADPH, CO2 and 5-C sugars
The pentose phosphate pathway (PPP)
Phase II Non-oxidative
- Reversible
* Produces 3-carbon sugars
Importance of The pentose phosphate pathway (PPP)
- NADPH production
- reductive biosynthesis (e.g. FA biosynthesis)
- removal of hydrogen peroxide (free radicals)
- reduction of abnormally formed disulphide bonds
- cytochrome P450 enzyme function
- phagocytosis by white blood cell
- synthesis of nitric oxide
