BB17 Glycolysis Flashcards
Glycolysis is an
energy conservation pathway
Glycolysis
- sequence of reactions that converts glucose into pyruvate
* relatively small amount of ATP produced
The chemical intermediates in glycolysis are either
six-carbon units
• derivatives of glucose or fructose
three-carbon units
• derivatives of glyceraldehydes, dihydroxyacetone, glycerate, pyruvate
All intermediates are phosphorylated with the phosphoryl groups linked as either
esters
anhydrides
••phosphorylation activates these intermediates
Stages of glycolysis
Stage 1 – trapping of glucose and its destabilization
Stage 2 – breakdown of a six-carbon unit to create 2 three-carbon units
Stage 3 – generates ATP
Stage 1
• traps glucose, forms a compound easily broken down into phosphorylated 3-C units
- add phosphate to trap and destabilize (glucose-6-phosphate)
- isomerization
(fructose-6-phosphate) - further phosphorylation (fructose-1,6-bisphosphate)
… adds phosphate to glucose to make glucose-6-phosphate
Hexokinase
Isomerization of
glucose-6-phosphate to
fructose-6-phosphate
catalyzed by
phosphoglucose isomerise • opens 6-membered ring • catalyzes the isomerisation • promotes the formation of a 5-membered ring * still 6 carbons – 1 is a side group
Second phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate catalyzed by
phosphofructokinase
Fructose-1,6-bisphosphate
molecule that’s easily cleaved into two 3-carbon units
Stage 2
produces two different 3-carbon units that are interconvertible
… cleaves
fructose-1,6-bisphosphate
into two 3-carbon units
aldolase
Fructose-1,6-bisphosphate is cleaved into
- glyceraldehydes 3-phosphate (on glycolytic pathway)
* dihydroxyacetone phosphate (not on glycolytic pathway)
Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate
• can be interconverted in an isomerisation process
• catalyzed by triose phosphate isomerise
(Tim-barrel)
Product of stage 2
2 x glyceraldehyde 3-phosphate
Stage 3
produces ATP
2x
4 ATP – 2ATP from stage 1
= 2 ATP gained
Stage 3
• 5 steps
1. glyaldehyde 3-phosphate
=>1,3-bisphosphoglycerate
(1,3-BPG)
2. 1,3-BPG
=> 3-phosphoglycerate
3. 3-phosphoglycerate
=> 2-phosphoglycerate
4. 2-phosphoglycerate
=> phosphoenolpyruvate
5. phosphoenolpyruvate
=> pyruvate + ATP
forms 2 ATP but repeated = 4 ATP
Oxidation of glyceraldehyde 3-phosphate to
1,3-bisphosphoglycerate
• catalyzed by glyceraldehyde 3-phosphate dehydrogenase
• requires reduction of NAD+ to NADH
1,3-BPG is a
high-potential phosphorylated product
• more energy released when losing phosphoryl group than in creating bond to make ATP from ADP
A phosphoryl group is transferred from 1,3-BPG to ADP, forming
3-phosphoglycerate and ATP
• catalyzed by phosphoglycerate kinase
A phosphoryl shift occurs in the conversion of 3-phosphoglycerate to
2-phosphoglycerate
• catalyzed by phosphoglycerate mutase
• 2-phosphoglycerate is less stable
A dehydration converts
2-phosphoglycerate to
phosphoenolpyruvate
• catalyzed by enolase
• phosphoenolpyruvate is another high-potential phosphorylated compound
A phosphoryl group is transferred from phosphoenolpyruvate to ADP, forming
pyruvate and ATP • losing phosphoryl = pyruvate in unstable enol form • rearranges to pyruvate • catalyzed by pyruvate kinase • virtually irreversible reaction
The net reaction in the transformation of glucose into pyruvate is
• Glucose • 2Pi • 2 ADP • 2 NAD+ = • 2 Pyruvate • 2 ATP • 2 NADH • 2H+ • 2 H2O
One glucose molecule generates
2 molecules of ATP
2 molecules of pyruvate
The reactions of glycolysis
(energetically favourable) are coupled to
the synthesis of ATP (energetically unfavourable)
via shared chemical intermediate
There are 2 positions where ATP is formed
1) 1,3-Bisphosphoglycerate to 3-phosphoglycerate
• 1,3-BPG passes phosphate to ADP
= substrate level phosphorylation
2) the phosphoenolpyruvate to pyruvate
• loss of phosphate makes pyruvate in an unstable enol form
• free energy released on the arrangement of pyruvate into its more stable ketone form is more than is needed to produce ATP
Glycolysis regulation reflects its dual role in
- degrading glucose to make ATP
* providing building blocks for biosynthetic reactions (ie formation of long chain fatty acids)
In metabolic pathways, enzymes catalyzing… are potential sites of control/regulation
essentially irreversible reactions
Reactions catalyzed by…are virtually irreversible
- Phosphofructokinase
- Hexokinase
- Pyruvate kinase
Activities of control sites are regulated by
- reversible allosteric control (ie feedback inhibition) – in milliseconds
- reversible covalent modifaction (ie phosphorylation) – in seconds
- transcriptional control – in hours
The most important controlling element in the glycolytic pathway of mammals is
Phosphofructokinase
2 features of the phosphofructokinase enzyme
1) regulation of ATP production
2) regulation to provision of building blocks
Phosphofructokinase regulation of ATP production
• allosteric inhibition by high levels of ATP
• allosteric activation by high levels of AMP
(glycolysis is stimulated as the energy charge falls)
• to prevent excess formation of lactate the enzyme is also inhibited by H+ (low pH)
Phosphofructokinase is stimulated by
fructose 2,6-bisphosphate
• a molecule produced only when glucose is abundant
Phosphofructokinase regulation of provision of building blocks
the enzyme is inhibited by citrate, an early intermediate in the citric acid cycle
Other enzymes that regulate glycolysis
- hexokinase
* pyruvate kinase
Hexokinase
inhibited by increased levels of glucose 6-phosphate
fructokinase 6-phosphate
• ie when phosphofructokinase is inactive
Fructose 1,6-bisphosphate
activates pyruvate kinase
ATP
allosterically inhibits pyruvate kinase
feed-forward activation
