Glycolysis Flashcards
What is glycolysis ?
A key pathway in preparing glucose (and other CHO) for oxidative degradation.
A series of reactions.
Glycolysis - sugar splitting
What happens in glycolysis ?
Transport of glucose
Blood glucose is transported into cells (e.g. Glut2 and Glut4 - enhanced by insulin), lowering blood concentrations.
Where does glycolysis take place ?
In the cytosol of the cell
Describe some fates of glucose within the cell
Glycolysis
Glycogen
Fat
Glycolysis
Catabolism
Glycogen
Anabolism
Fat
Anabolism
What is the aim of glycolysis ?
One molecule of glucose is converted into 2 molecules of pyruvate.
Pyruvate is then converted into acetyl co-enzyme A, which enters the Citric Acid Cycle.
State the stages of Glycolysis
Investment
Cleavage
Energy Harvest
How much energy is required for glycolysis ?
2 ATP are required for early reactions
State the net yield of ATP generated by glycolysis
4 ATP are generated later, giving a NET YIELD of :
2 ATP per glucose
How many carbon molecules are in pyruvate and glucose ?
Pyruvate - 3
Glucose - 6
Describe the 2 fates of pyruvate produced from glycolysis
In AEROBIC conditions :
- pyruvate enters the citric acid cycle
- converted to acetyl-co-enzyme A
IN ANAEROBIC (low oxygen) conditions :
- Lactate is formed from pyruvate (fermentation)
State the strategy for the glycolysis pathway
- Add phosphoryl groups to glucose and intermediates
- Chemically convert phosphorylated intermediates to compounds with high energy phosphate bond potential.
- Chemically couple the hydrolysis of reactive compounds to generate ATP (and NADH+ and H+)
Describe step 1 of Glycolysis
Phosphorylation of glucose at carbon 6
Requires ATP (INVESTMENT STAGE)
Locks glucose inside the cell
(maintains glucose gradient)
Describe step 2 of Glycolysis
Conversion of glucose-6-P to fructose-6-P
G-6-P ring structure opens to enable isomerisation and subsequent ring closure. F-6-P
(G-6-P : Glucose 6 phosphate)
Describe step 3 of Glycolysis
Fructose 6 phosphate is phosphorylated at carbon 1, and becomes fructose 1,6-biphosphate (FBP)
Requires ATP (INVESTMENT phase)
Phosphofructokinase (PFK) key regulatory point
Describe step 4 of Glycolysis
Aldolase cleaves the FBP into 2x trioses
Glyceraldehyde-3-phosphate (GAP)
Dihydroxyacetone phosphate (DHAP)
Describe step 5 of Glycolysis
DHAP is readily converted into GAP
2 GAPs for every glucose molecule.
Glyceraldehyde-3-phosphate (GAP)
Dihydroxyacetone phosphate (DHAP)
Describe step 6 of Glycolysis
Oxidation and Phosphorylation of GAP by NAD+ and Pi
First ‘high energy’ intermediate-aldehyde oxidation (exergonic reaction)
This drives the synthesis of the 1-3 bisphosphoglycerate
Describe step 7 of Glycolysis
First formation of ATP (energy harvest)
The newly formed high-energy phosphate bond used to synthesise ATP and 3-phosphoglycerate (3PG)
Describe step 8 of Glycolysis
3PG converted to 2PG
This is essential preparation for the next energy harvest step.
Describe step 9 of Glycolysis
2PG dehydration to form phosphoenolpyruvate (PEP)
Converts low energy phosphate ester bond of 2PG into high-energy intermediate phosphate bond
Describe step 10 of Glycolysis
Hydrolysis of PEP high-energy bond generates ATP and pyruvate.
This is a physiological irreversible reaction
e.g. of substrate level phosphorylation
Describe the energy yield from glycolysis
Glycolysis releases relatively little energy from glucose - the majority is released during the final stage, electron transfer chain and oxidative phosphorylation.
What happens to pyruvate under anaerobic conditions ?
Converted to lactate
What happens to pyruvate under aerobic conditions ?
Pyruvate is transported to the mitochondrial matrix and converted to acetyl-coenzyme A, which feeds into the citric acid cycle.
NADH+ and H+ are oxidised to replenish NAD+ via the electron transport chain.
When cellular energy levels (ATP) in excess, acetyl-coenzyme A used for synthesis of fatty acids.
What happens to pyruvate under high cellular energy levels ?
Fatty acids or ketone bodies
Describe lactate production in anaerobic conditions
For glycolysis to continue in anaerobic conditions, NAD+ must be replenished.
When ATP demand is high and oxygen is depleted, homolactic fermentation regenerates NAD+
Reversible reaction which enables glycolysis to continue for short amounts of time.
The build up of lactate causes muscle cramps and limits activity.
Slow/fast twitch myofibre composition determines the rate of muscle fatigue.
What type of reaction is the production of lactate ?
A redox reaction
Oxidisation of NADH into NAD
Reduction of pyruvate into lactate
A highly exergonic reaction
Describe the structure of lactate dehydrogenase
Composed of 2 different types of subunit : H or M
5 isozymes - Tissue specific expression
Tetrameric - different combinations of subunits combine
What does the presence of lactate dehydrogenase in the blood indicate ?
Gives an indication of where in the body damage has occurred.
What does tetrameric mean ?
Different combinations of subunit combine.
Describe lactate dehydrogenase in aerobic conditions
LDHB gene –> subunit H
Chromosome 12
H subunits found in the heart tissue
Describe lactate dehydrogenase in anaerobic conditions
LDHA gene –> subunit M
Chromosome 11
M subunits found in muscle tissue
State the use of lactate dehydrogenase in diagnosis
Differing properties and tissue locations
Damage to specific tissues releases cell contents into circulation.
Changes in serum levels - aids disease diagnosis
Where is LDH 1 found ?
Predominantly / only found in cardiac tissue (also RBCs and kidneys)
Elevated in myocardial infarction
Fastest moving
Where is LDH 5 found ?
Skeletal muscle, Liver
Elevated in skeletal muscle and liver diseases
Slowest moving
State ways in which the rate of glycolysis is controlled
Key enzymes
High ATP inhibit enzyme activity
Intermediate substrates (e.g. fructose-6-P) stimulate PFK activity
High citric acid inhibits
Low pH inhibits
Hormones
State the key regulatory enzymes involved in glycolysis
Hexokinase
PFK
Pyruvate kinase
Function of hexokinase
Locking glucose into the cell
Describe hexokinase
What is it inhibited by ?
Allosterically inhibited by G-6-P
Describe phosphofructokinase
What is it activated and inhibited by ?
Most IMPORTANT site of control
- first step unique to glycolysis
High [ATP] inhibits PFK : allosterically bind a region separate from the active site
High [AMP] activates PFK (2ADP –> ATP + AMP)
Function of phosphofructokinase
1st step unique to glycolysis
Describe pyruvate kinase
What is it activated and inhibited by ?
Inhibited by high ATP and alanine and activated by FBP
Function of pyruvate kinase
Last step from high energy compound into pyruvate
