WEEK 1: Glycolysis and pyruvate dehydrogenase complex Flashcards
what is cellular respiration?
the oxidation of glucose to form ATP
what is glycolysis?
first step of cellular respiration that is the breakdown of sugar.
Glucose —> Pyruvate
one 6-carbon molecule of glucose into two 3-carbon molecules of pyruvate
why is glycolysis significant? (5)
- principal route for glucose and other hexose metabolism
- it is the only pathway that takes place in all cells of the body
- it is the only energy source for erythrocytes
- it provides carbon skeletons for synthesis of non-essential amino acids
- most of the reaction of the glycolytic pathway are reversible
how long can glycolysis support strenuous activity?
2 mins
how is cardiac muscle adaptive for anaerobic performance?
- does not fatigue like skeletal muscle
- has low glycolytic activity
is glycolysis anaerobic or aerobic?
anaerobic
as strenuousness of activity increases, what happens to the ratio of aerobic exercise compared to anaerobic exercise?
anaerobic glycolysis provides energy for activity almost entirely, then decreases as aerobic activity increases simultaneously.
what happens during anaerobic activity? (5)
- production of NADH exceeds the capacity of the electron transport chain
- pyruvate is converted to lactate by lactate dehydrogenase
- this converts NADH back into NAD+, lowering the level of NADH
- reduces intracellular pH
- lactate diffuses out into bloodstream and is processed by the liver to produce glucose
what would the lactate levels be of someone that is untrained compared to someone that is trained or an athlete after completing endurance training?
the lactate levels would be higher
where is the site of glycolysis?
it occurs in the cytosol
what are the first 5 steps of glycolysis known as?
energy investment step (think of the ripcord for a motor to start)
what are the next 5 steps (6-10) of glycolysis known as?
energy generation
what occurs in the first step of glycolysis?
hexokinase reaction - phosphorylation of the hexoses (mainly glucose)
why is glucose converted in the first step?
converting it keeps the level of glucose low, so more glucose will enter the cell.
it is prevented from leaving the cell due to the charge the phosphate adds to the molecule.
where does the phosphate group come from in most steps of glycolysis?
ATP donates it but must be associated with Mg.
APT converts into ADP
when ATP converts into ADP, what is being donated?
phosphate
why must ATP be associated with Mg?
when Mg is not associated, there is no Mg-ATP complexed. With out the substrate, un-complexed ATP is a potent inhibitor of hexokinase.
how does hexokinase catalyse the first step?
by proximity effect - brings 2 substrates in close proximity
what inhibits hexokinase at the end of the first step?
inhibited by high concentration of product (G6P) compared to substrate
give differences between hexokinase and glucokinase.
Hexokinase
-Km low, high affinity for glucose
- Non-specific, can phosphorylate any of hexoses
- Present in tissues, supplies glucose to tissues even in low blood glucose concentration
- Not affected by insulin
- Allosterically inhibited by glucose
Glucokinase
- Km high, low affinity for glucose
- Specific, can phosphorylate only glucose
- Present in liver only
- Helps drive movement of glucose from blood to cells after meal.
- Stimulated by glucose and insulin
- Not inhibited by glucose-6-phosphate
what occurs in the second step of glycolysis?
isomerization of glucose-6-phosphate to fructose-6-phosphate
what is the enzyme needed in step 2 of glycolysis?
phosphoglucose isomerase
what cofactor does phosphoglucose/phosphohexose isomerase (PGI) require for activity?
Mg2+
what other roles does PGI have?
- neural growth factor
- driver of cancer metastasis and maturation
what occurs in the third step of glycolysis?
transfer of phosphate group from ATP to C-1 of F6P to produce Fructose 1,6 bisphosphate
what step is the first irreversible step?
glucose to g6p
what enzyme catalyses step 3?
Phosphofructokinase-1 check on ninja nerd
what activates Phosphofructokinase-1 in step 3?
fructose 2,6 biphosphate, ADP and AMP
what occurs in step 4 of glycolysis?
splitting of fructose 1,6 bisphosphate into glyceraldehyde 3 phosphate and dihydroxy acetone phosphate (isomers)
conversion of aldose to ketose
what enzyme catalyses step 4?
aldolase
does step 4 require energy?
yes
what occurs in step 5 of glycolysis?
Conversion of Dihydroxyacetone phosphate to glyceraldehyde 3 Phosphate
what enzyme catalyses step 5?
Triose phosphate isomerase
give a summary of the first 5 step of glycolysis (one word answer for each step).
phosphorylation
isomerisation
phosphorylation
cleavage/splitting
isomerisation
what occurs in step 6 of glycolysis?
Conversion of GAP to Bisphosphoglycerate
what enzyme catalyses step 6?
Glyceraldehyde-3-phosphate dehydrogenase
what groups are added in step 6?
2 phosphate groups
how is step 6 an energy yielding step?
inorganic phosphate is incorporated in the reaction without any use of ATP
what does NAD+ do in step 6?
it is the cofactor which acts as an oxidising agent.
NAD+ —> NADH + H
what occurs at step 7 of glycolysis?
Transfer of phosphoryl group from 1,3 bisphosphoglycerate to ADP generating ATP
what enzyme is required for step 7?
Phosphoglycerate kinase
is step 7 reversible?
yes
how does step 7 generate ATP?
SUBSTRATE-LEVEL PHOSPHORYLATION
what occurs in the 8th step of glycolysis?
Conversion of 3-phosphoglycerate to 2-phosphoglycerate
what enzyme is required for step 8?
Phosphoglycerate Mutase
what occurs at step 9 of glycolysis?
Dehydration of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP)
enzyme is required for step 9?
Enolase
what occurs in step 10 of glycolysis?
Transfer of phosphoryl group from PEP to ADP generating ATP and Pyruvate.
enzyme is required for step 10?
Pyruvate Kinase
2 steps of glycolysis produce ATP?
7 and 10
give a summary of steps 6-10 of glycolysis (one word answer for each step).
oxidation and phosphorylation
substrate level phosphorylation
substrate level phosphorylation
isomerisation
dehydration
how much ATP is produced and why?
energy investment phase produces 2 molecules of glyceraldehyde-3-phosphate.
double 2 ATP productions we see (7 and 10), 4 ATP is produced
what happens to the 2 NADH molecules produced?
they are oxidised in the mitochondria under aerobic conditions
if 2 NADH are oxidised in the mitochondria under aerobic conditions, how many molecules of ATP can be synthesized from their free energy?
6
how does insulin stimulate step 1 and step 2?
Insulin stimulate Hexokinase & Glucokinase by converting glucose to glu-6-PO4
Insulin stimulate Phosphofructokinase converting fru-6-PO4 to Fru-1,6 bisphosphate
how does glycolysis stimulate step 2?
Glucagon stimulate liver glu-6-PO4 by converting glu-6-PO4 to glucose & fru-1,6- bisphosphate.
inhibitors? do i need to know
what are the two types of control for metabolic reaction?
substrate limited
enzyme limited
what does substrate limited mean?
When concentrations of reactant and products in the cell are near equilibrium, substrate availability drive reaction rat
what does enzyme limited mean?
When concentration of substrate and products are far away from the equilibrium, then it is activity of enzyme that decides the rate of reaction
what 3 enzymes work comparatively slower and may limit glycolysis?
I. The hexokinase (HK)
II. The phosphofructokinase (PFK)
III. The pyruvate kinase
how many molecules of pyruvate are produced from one molecule of glucose?
2
where does aerobic respiration take place
mitochondria
what happens to pyruvate once it enters the mitochondria?
pyruvate undergoes oxidative decarboxylation
what is the chemical eq for the oxidative decarboxylation of pyruvate?
Pyruvate + NAD+ + CoA –> acetyl CoA + NADH + CO2
what enzyme complex catalyses the oxidative decarboxylation of pyruvate in the mitochondria?
pyruvate dehydrogenase complex
is the oxidative decarboxylation of pyruvate in the mitochondria reversible or irreversible?
irreversible
what 3 enzymes make up the pyruvate dehydrogenase complex?
E1 = pyruvate dehydrogenase
E2 = dihydrolipoamide transacetylase
E3 = dihydrolipoamide dehydrogenase
what happens during starvation?
circulating blood glucose levels are lower.
glucose becomes scarce.
PDC is activated by PDK to ensure there is better utilisation of fats as an energy source.
Tries to spare bodily stores of glycogen and glucose as well.
what does calorimetry measure?
heat
