Glycolysis (Carbohydrate catabolism) Flashcards
Glucose-6-phosphate has 3 fates
1) Stockage of glucose (as glycogen)
2) Used in glycolysis
3) Pentose Phosphate Pathway
Glycolysis
Pathway where 6-carbon sugars are split to yield a 3-carbon compound (pyruvate)
T or F: During glycolysis the potential energy store in these six-carbon sugars is used in the synthesis of ATP from ADP
True
What 2 conditions does glycolysis occur under
- Anaerobic
- Aerobic
2 origins of the sugars used in glycolysis
1) In food stores - Digestion of polysaccharides (Starch and glycogen) and disaccharides (sucrose, maltose, lactose)
2) Metabolism - Non-carbohydrate precursors (gluconeogenesis in the liver and kidney)
Reactions 1-5 of glycolysis are part of the
Energy Investment Phase
Reactions 6-10 of glycolysis are part of the
Energy Generation Phase
Reaction 1 of glycolysis
α-D-Glucose is phosphorylated to form α-D-Glucose-6-phosphate (G6P) by hexokinase (enzyme)
Name 4 characteristics of reaction 1 of glycolysis
- Investment of ATP because reaction is initially not favourable
- Mg2+ makes it more favourable for phosphate to bind to form ATP
- Becomes highly favourable with ATP investment
- IRREVERSIBLE (-18.4kj/mol)
Km
Concentration at half of Vmax (maximum speed of enzyme will be reached)
Reaction 1 is catalyzed by
Hexokinases
Name the 4 types of hexokinases found in mammals
Hexokinas I-IV
4 characteristics of hexokinase I, II, and III
- Found in multiple tissues but mainly located in skeletal muscle.
- Not specific to glucose (could used other substrates like fructose and mannose).
- Low KM enzymes meaning they have strong affinity (around 0.04mM) = tiny concentration of glucose means enzyme uses immediately
- They are strongly inhibited by the product of the reaction, glucose-6-phosphate (negative feedback when product becomes in great quantities because waste of energy to produce more
T or F Hexokinase I, II, and II react to only high concentrations of glucose
False, they will react to very little concentrations of glucose because the muscles need energy right away (Eg. Once start running use lots of glucose (enzymes activated), then when stop running glucose consumption stops and products form to inhibit enzymes)
T or F Hexokinase I, II, and II react to only high concentrations of glucose
False, they will react to very little concentrations of glucose because the muscles need energy right away (Eg. Once start running use lots of glucose (enzymes activated), then when stop running glucose consumption stops and products form to inhibit enzymes)
** Intracellular glucose concentration is normally around 2-15mM so hexokinase I-III are operating at saturating substrate concentration
T or F: Muscle glucose intake must be controlled to prevent starvation of the brain’s energy
T
T or F: Muscle glucose intake must be controlled to prevent starvation of the brain’s energy
T
Hexokinase IV is alco called
Glucokinase
Hexokinase IV/Glucokinase 5 characteristics
- Found in the liver and pancreas
- Glucose specific
- High KM enzyme, low affinity (around 7.5mM reach half Vmax)
- Allow the liver to adjust its rate of glucose usage to the variations in blood glucose levels.
- Not inhibited by Glucose-6 phosphate
Liver and pancreas adjust to glucose levels in the bloodstream to
regulate a constant supply of glucose to the blood (adjusts to any concentration of glucose increase or decreases
2 functions of liver in terms of glucose synthesis or storage
- Can store glucose as glycogen to decrease blood glucose
- Can break down glycogen to increase blood glucose
Explain the difference in glucose concentrations needed for hexokinase I-III and hexokinase IV
Glucose Transporters (GLUT)
move glucose molecules across the plasma membrane
T or F: There is more than 12 glucose transporter expressed in various tissues and having slightly different roles.
T
High Insulin levels means
High glucose levels are present (must store) in the muscle
High glucagon levels means
Low glucose levels present in the muscle
4 characteristics of GLUT2 transporters
- Found in the liver, pancreas and kidney
- Insulin independent
- Quickly equilibrates concentration of glucose across plasma membrane
- Allow the hexokinase IV to adjust its rate to the concentration of glucose in the blood
3 characteristics of GLUT4 transporters
- Found in the skeletal muscle, adipose tissues and heart
- Regulated by insulin, but also epinephrine
- In absence of sugar, this transporter is sequestered. It is released upon insulin presence
Blood glucose concentration vs hexokinase activity
Glycolysis Reaction 2
α-D-Glucose-6-phosphate (G6P) is isomerized into D-Fructose-6-phosphate (F6P) by the phosphohexose isomerase. (delta G =1.7kj/mol)
Is glycolysis reaction 2 reversible or irreversible
reversible
What reactions help push reaction 2 into the forward/favourable direction
1) Reaction 1 is so favourable it will push reaction 2 into a favourable reaction because so much reactant of glucose so it will convert G6p to F6P even though it is considered reversible (move in forward direction)
2) Reaction 3 also aids reaction 2, because reaction 3 is so favourable that it will instantly convert F6P to FBP
Which step of glycolysis is the commiting step and the rate limiting (regulating step)
Reaction 3
Reaction 3 of glycolysis
D-Fructose-6-phosphate (F6P) is phosphorylated at C-1 by the phosphofructokinase 1 (PFK) to generate D-Fructose-1,6-bisphosphate (FBP)
3 characteristics of reaction 3 glycolysis
- Consumes an ATP
- Highly favourable (delta G = -15.9 kJ/mol)
- Irreversible
Reaction 4 glycolysis
D-Fructose-1,6-bisphosphate (FBP) (aldolase) is cleaved to generate two 3-carbons (3C) molecules : Glyceraldehyde-3-phosphate (GAP) and Dihydroxyacetone phosphate (DHAP)
Fructose-1,6-biphosphate aldolase is also called
aldolase
Characteristics of reaction 4
- Strongly endergonic so it requires energy to proceed (should never occur under standard state conditions (+23.9 kJ/mol)
- With the help of energy investments in cell conditions it becomes favourable (-1.3 kJ/mol)
- Reversible
Can you explain the discrepancy between the standard and actual delta G of reaction 4 (+23.9kj/mol vs -1.3 kj/mol)
This reaction can move in this direction if there is an increase in reactant (FBP) or a decrease in product (DHAP and GAP) that in turn decreases the standard delta g to make it something more close to a reversible reaction instead of irreversible
Reaction 5 glycolysis
Isomerization of the Dihydroxyacetone phosphate (DHAP) to Glyceraldehyde-3-phosphate (GAP) by the Triose phosphate isomerase (TPI)
Reaction 5 characteristics
- Weakly endergonic (requires energy to proceed)
- ΔGo’ = +7.6kJ/mol (standard state conditions)
- ΔG = ~ 0kJ/mol in cell conditions
- Reversible
Reaction 5 characteristics
- Weakly endergonic (requires energy to proceed)
- ΔGo’ = +7.6kJ/mol (standard state conditions)
- ΔG = ~ 0kJ/mol in cell conditions
- Reversible
In reaction 5 going from DHAP to GAP, what group is change
Goes from ketone (DHAP) to an aldehyde (GAP)
How can a reaction that is highly endergonic move in an favourable direction?
having exergonic reaction before or after, increasing reactant or product of reaction
Eg. Reaction 3 has an effect on reaction 4 and 5 and 6 to make it favourable and push it in the forward direction
In the energy investment phase (First 5 reactions of glycolysis( what is the total net ATP, glucose and glyceraldehyde-3-phosphate used/made
1) two ATP molecules are used to convert
2) one molecule of glucose to
3) two molecules of glyceraldehyde-3-phosphate
Energy generation phase (Reaction 6-10)
Reaction 6 of glycolysis
Oxidation and phosphorylation of Glyceraldehyde-3-phophate (GAP) to generate 1,3-bisphosphoglycerate (BPG)
**Need inorganic phosphate with GAP to produce BPG
(Dont memorize intermediates)
Cysteine held in place by enzyme
What catalyzes reaction 6 of glycolysis
Reaction is catalyzed by the Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a coenzyme, NAD+ (Nicotinamide adenine dinucleotide)
*NAD+ is an electron acceptor for the oxidation reaction
Characteristics of reaction 6 glycolysis
1.ΔGo’ = +6.3kJ/mol (standard state conditions)
2. Reversible
OILRIG
Oxidation Is a Loss (of electrons); Reduction Is a Gain (of electrons)
Reaction 7 glycolysis
Synthesis of an ATP by the transfer of a phosphoryl group from 1,3-bisphosphoglycerate (BPG) to produce 3-phosphoglycerate (3PG).
Reaction 7 is catalyzed by
Phosphoglycerate kinase
Characteristics of reaction 7
- ΔGo’ = -17.2kJ/mol (standard state conditions)
- ΔG = around 0 kJ/mol in cell conditions
- Reversible
- It is pulling on the reactants from reaction 5 and 6 to push the reaction 7 product to the following reactions 8 and 9 to push in the forward direction, that is why delta G is close to 0kJ/mol in cell conditions
Reaction 8 glycolysis
Isomerization of 3-phosphoglycerate (3PG) into 2-phosphoglycerate (2PG) by the phosphoglycerate mutase
Characteristics of reaction 8
- 3PG concentration is kept high by reaction 6 and 7 (mostly 7) driving forward reaction 8.
- ΔGo’ = +4.4kJ/mol (standard state conditions)
- Moving phosphate to carbon 2 from carbon 3
Characteristics of reaction 8
- 3PG concentration is kept high by reaction 6 and 7 (mostly 7) driving forward reaction 8.
- ΔGo’ = +4.4kJ/mol (standard state conditions)
- Moving phosphate to carbon 2 from carbon 3
Reaction 9 glycolysis
Dehydration of 2-phosphoglycerate (2PG) in phosphoenolpyruvate (PEP) by the enolase
**condensation reaction (removal of water)
Characteristics of reaction 9
- ΔGo’ = -3.2kJ/mol (standard state conditions)
- Reversible
- PEP concentration kept low by pyruvate kinase in next step in order to push forward (use all the reactant for reaction 10)
Reaction 10 glycolysis
Synthesis of an ATP by the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) by the pyruvate kinase producing pyruvate
Characteristics of reaction 10 glycolysis
- ΔGo’ = -29.7kJ/mol (standard state conditions)
- Irreversible
Pyruvate has 2 chemical groups, what are they?
- Ketone
- Carboxylic acid
Metabolic (net) yield of glycolysis
Rxn 1-5: 2 ATP invested
Rxn 6-10: 4 ATP and 2 NADH produced
1 Glucose -> 2 pyruvate
What are the 3 fates of pyruvate
Goes to either:
1. Aerobic glycolysis
2. Anaerobic glycolysis
3. Gluconeogenesis
T or F: Glycolysis was not the first energy yielding pathway utilized by the earliest known organisms, when the atmosphere was still anaerobic
False it was
How many ATP does anaerobic glycolysis yield
2 ATP (low energy efficiency) per 1 glucose
How many ATP does aerobic glycolysis yield
30-32 ATP (high energy efficiency) per 1 glucose
Aerobic glycolysis
Anaerobic glycolysis
Fermentaion (anaerobic glycolysis)
Anaerobic degradation of a nutrient (glucose), with no net change in the oxidation state, to produce energy. (NADH that was produced by glycolysis will be used up)
2 types of fermenation
- Lactic fermentation: Reduction of pyruvate to lactate
- Alcoholic fermentation: Reduction of pyruvate to ethanol
T or F: In 100-200m sprints your muscle will never use oxygen
True, muscle usually takes 1 minute of energy output (exercise) for it to be aerobic instead of anaerobic
-First minute of exercise is anaerobic, generate energy without consuming oxygen
Lactic fermentation characteristics
- Generation of energy (ATP) without consuming oxygen
- No net change in oxidation state of the sugars
- Reduction of pyruvate to lactate
- Regenerates NAD+ (reduction:gain of electrons) for further glycolysis under anaerobic conditions
Lactic fermentation pathway
- Reduction = break even for NADH and ATP = 0 = no net change occurs, use the energy we made
- Delta G standard because NADH is a lot of energy when broken down to NAD+ by lactate dehydrogenase
Lactic acid pathway in the body
- In the early moment of a strenuous exercise, lactate builds up in the muscle and the amounts of oxygen required doesn’t match the amount needed for aerobic glycolysis.
- The lactate produced will diffuse (recycles) through the tissue and travel to the liver via the bloodstream
- In the liver, lactate is catabolized through aerobic glycolysis or be converted to glucose through the Cori Cycle (gluconeogenesis)
Red blood cells rely on [blank] glycolysis and why
Red blood cells rely on anaerobic glycolysis since they lack mitochondria.
4 characteristics of lactate build up
- Conversion of lactate into glucose is costly so body needs oxygen and tons of ATP to convert all the lactate back to glucose because we are in debt
- Lactate is toxic to the body
- Lactate build up is due to lack of oxygen use = accumulates
- Don’t want lactate to accumulate so it needs to go to liver for conversion
4 characteristics of lactate build up
- Conversion of lactate into glucose is costly so body needs oxygen and tons of ATP to convert all the lactate back to glucose because we are in debt
- Lactate is toxic to the body
- Lactate build up is due to lack of oxygen use = accumulates
- Don’t want lactate to accumulate so it needs to go to liver for conversion
Lactic fermentation (anaerobic glycolysis) fate
- Lactate is used as a percursor for gluconeogenesis (Cori Cycle)
- Needs an investment of 6 ATP to convert back to glucose (because high energy molecule = cost energy)
- Net of 4 ATP because 2 ATP is produced by forming 2 lactate
- Lactate is still a high energy molecule because it only requires 4 ATP instead of 6 ATP to be converted back to glucose
Alcoholic fermentaion (anaerobic glycolysis) conversion of pyruvate to ethanol
- Decarboxylation (losing one carb to CO2)
- Aldehyde is converted to alcohol
Alcoholic fermentation (anaerobic glycolysis) pathway
Acetaldehyde and ethanol are added to the end after pyruvate = no net change in oxidative state (exact same as lactic fermentation, but we lose one carbon along the way (technically 2 because 2 pyruvate) to produce 2 ethanol)
Energy balance sheets of 4 reactions
Don’t need to memorize but know difference
Aerobic = 32 ATP produced and very – delta G (high energy)
Glucose to pyruvate = small – delta G
Glucose to lactic acid = small – delta G
Glucose to ethanol = small – delta G
We invest a lot more energy in first reaction, compared to last 3, so we need aerobic respiration because it produces such a high amount of energy
Energy profile of anaerobic glycolysis
Reaction 4-9 is reversible but can tilt reaction in forward reaction by how much product is produced by reaction 3 and how much product is used as a reactant in reaction 10
Free energy change table of glycolytic reactions
NOTE: Reaction 7 delta G ends up being 0 because it helps pull reaction 4,5, and 6, and push reaction 7 and 8
