Glycolysis and PDH Flashcards
1
Q
Glycolysis
A
- splitting of 1 6-carbon glucose into 2 3-carbon pyruvate molecules
- NAD+ is reduced to NADH
2
Q
Aerobic glycolysis
A
- when O2 supply is plentiful, NADH reoxidised to NAD+ via mitochondria
- pyruvate taken up by mitochondria, metabolised to CO2 and H2O via TCA cycle
3
Q
Anaerobic glycolysis
A
- NADH production exceeds the capacity of the electron transport chain
- Pyruvate is converted to lactate by lactate dehydrogenase
- Converts NADH back into NAD+, lowering the level of NADH
- Reduces intracellular pH
- Lactate diffuses out into bloodstream & is processed by the liver to produce glucose
4
Q
Significance of glycolysis
A
- only pathway that takes place in all cells of the body
- only source of energy in erythrocytes and only fuel normally used by neurones
- provides carbon skeletons for synthesis of non-essential amino acids as well as glycerol part of fat
- Most reactions of glycolytic pathway are reversible, which are used for gluconeogenesis
5
Q
Glycolysis in exercise
A
- Rapid formation of energy during short-term strenuous exercise: glycolysis could support activity up to c. 2 minutes
- Cardiac muscle is adapted for aerobic performance: doesn’t fatigue like skeletal muscle, has low glycolytic activity, rapidly damaged under ischaemic conditions
6
Q
Site of glycolysis
A
- occurs in the cytosol of all the cells of the body
7
Q
Two phases of glycolysis
A
- energy investment (reactions 1-5)
- energy generation (reactions 6-10)
8
Q
Energy investment (reactions 1-5)
A
- sugar phosphates are synthesised at the expense of ATP -> ADP
- the sugar is metabolically activated by phosphorylation
- 6C split into 2x3C sugar phosphates (triose phosphates)
9
Q
Energy generation (reactions 6-10)
A
- further activation of triose phosphates to energy-rich compounds
- reduced electron carriers are generated (NADH)
- the energy-rich compounds then transfer phosphate to ADP to form ATP = substrate-level phosphorylation
10
Q
Substrate-level phosphorylation
A
- generation of an energy-rich phosphate bond driven by the breakdown of a more energy-rich substrate
11
Q
Hexokinase reaction: phosphorylation of hexoses (mainly glucose)
A
- Hexokinase is present in most cells.
- In liver, Glucokinase is the main hexokinase (both ISOENZYMES) which prefers glucose as substrate
- It requires Mg-ATP complex as a substrate. Uncomplexed ATP - potent competitive inhibitor of this enzyme.
- Enzyme catalyses the reaction by bringing the two substrate in close proximity.
- This enzyme undergoes large conformational change upon binding with glucose. It is inhibited allosterically by G6P.
12
Q
Hexokinase
A
- 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 effected by insulin
- Allosterically inhibited by glucose
13
Q
Glucokinase
A
- 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
14
Q
Phosphohexose Isomerase: Isomerization of Glucose-6-Phosphate (G6P) to Fructose-6-phosphate (F6P)
A
- catalyses the reversible isomerization of G6P - (an aldohexose) to F6P - (a ketohexose)
- requires Mg++ for its activity.
- specific for G6P and F6P
- extracellular PGI have multiple additional roles in health and disease: neural growth factor, driver of cancer cell metastasis and maturation
15
Q
Phosphofructokinase-1 (PKF-1) Reaction: Transfer of phosphoryl group from ATP to C-1 of F6P to produce Fructose 1,6 bisphosphate
A
- important irreversible, regulatory step.
- PFK-1 is one of the most complex regulatory enzymes, with various allosteric inhibitors and activators.
- ATP is an allosteric inhibitor, and Fructose 2,6 biphosphate is an activator of this enzyme.
- ADP and AMP also activate PFK-1 whereas citrate is an inhibitor.
- PFK-1 has 3 different sub-units whose distribution may be tissue-specific
