Glucose as a Fuel Molecule #2 Flashcards
Breif glycolysis overview
- the splitting of glucose
- conversion of one molecule of glucose (6 carbons) to two molecules of pyruvate (3 carbons)
- energy conserved in ATP and NADH
- pyruvate may be further metabolised aerobically or anaerobically
what are the two phases that glycolysis can be split into?
Energy investment phase:
- activation of glucose, getting the molecule into a form so energy can be captured
- requires 2ATP
- the molecule is split (1x6C to 2x3C) at the end of the investment phase
Energy payoff phase:
- after a conversion, both 3C molecules are processed the same way
- return on the investment
- making an ATP profit (4 ATP produced, so making 2 ATP extra overall)
- 4ADP go to 4 ATP and 2NAD+ go to 2NADH
what are the key reactions for the activation of glucose?
Glucose:
- hexokinase (- delta G)
(1st activation of glucose; ATP hydrolysis)
Glucose-6-phoasphate (G-6-P):
- glucsephasphate isomerase (+ delta G) (rearrangement, driven forward in pathway as not standard conditions)
Fructose-6-phosphate (F-6-P):
- phosphofrcutoknase (-delta G)
(second activation of glucose; ATP hydrolysis)
Fructose-1,6-biphosphate (FBP)
Describe the first reactions in the first step of glycolysis activation of glucose)
Reaction 1: Glucose + phosphate -> glucose-6-phosphate + H2O (+delta G)
- energetically unfavourable so coupled with another reaction
Reaction 2: ATP + H2O -> ADP + phosphate (-delta G)
Overall reaction:
Glucose + ATP -> glucose-6-phosphate + ADP (- delta G)
describe the second reaction in glycolysis (splitting or aldolase reaction)
has a low +delta G but the overall pathway is favourable so this step proceeds
- triose phosphate isomerase (rearrangement)
G-3-P is in equilibrium with DHAP but:
G-3-P is used in the energy payoff phase
- keeps G-3-P concentration low
- drives reaction from DHAP to G-3-P
what are the two different types of reactions involving ATP and ADP in glycolysis?
Substrate level phosphorylation:
- direct (A + ADP -> B + ATP)
- energy comes from substrate
- The direct use of energy from a substrate molecule stored drive the synthesis of ATP (or equivalent)
- One way to release the energy to drive a SLP is the cleavage of a high-energy phosphate ester bond on a substrate (however, this wouldn’t be good because then we would make 2ATP and have spend 2ATP, not gaining anything. so to add that bond we use coenzymes)
Oxidative phosphorylation:
- indirect (reduced co-enzymes)
describe NAD as a coenzyme
NAD: nicotinamide adenin dinucleotide
- a coenzyme required by some enzymes that catalyse redox reactions (including in glycolysis, fatty acid oxidation, citric acid cycle)
- derived from nicotine (vitamin B3)
Undergoes a two-electron reduction (with reducing equivelents)
NAD+ is the oxidised form
NADH is the reduced form, and carries 2xe- and 1xH+
- carries one electron on the nitrogen in the ring to get rid of the + charge, and carries the other one by making a bond with H on the opposite side of the ring
describe the third stage of glycolysis, the key reaction for making an ATP profit (involving the addition of a high energy bond with phosphate)
- NAD+ is reduced (provides oxidising power)
- phosphate from solution added to substrate
G-3-P goes to 1,3-BPG by using phosphate and reducing NAD+
- the addition of phosphate does not require ATP so we are now set up to make ATP profit
describe the fourth stage of glycolysis, the first substrate level phosphorylation
1,3-BPG goes to 3-phosphoglycerate (3PG) using a phosphoglycerate kinase)
- The 1# carbon phosphate of 1,3-BPG is very reactive
- Phosphate cleaved: releases energy (-delta G)
- energy used for substrate-level phosphorylation (ADP + P -> ATP) (+delta G)
- overall negative delta G (coupled reaction)
It is the energy that is making this a substrate level phosphorylation, not the fact that ADP + P goes to ATP
describe how arsenic poisons glycolysis
Arsenate substitutes for phosphate (because their structure is similar and the enzyme can’t tell the difference)
- G-3-P goes to 1-arsono-3 phosphoglycerate
- unstable, senate hydrolysed but energy not captured
- ATP not synthesised by pjsphoglyceate kinase
- no net gain of ATP in glycolysis (as the energy is just released as heat)
describe the fifth step in glycolysis
Rearrangement: getting the molecule into a form that enables the following reactions
3PG -> 2PG -> posphoenolpyruvate (PEP)
describe the sixth step in glycolysis, the second substrate level phosphorylation
PEP -> pyruvate via pyruvate kinase
- phosphate cleaved: releases energy (-ve delta G)
- energy used for substrate-level phosphorylation (ADP + P -> ATP) (+ve delta G)
- overall negative delta G
describe the overall features of the glycolysis reaction
Glucose _ 2NAD+ +2ADP + 2Pi -> 2 pyruvate + 2NADH + 2ATP + 2H+
Glycolysis overall: Delta G*’ = -73 kJ/mol
pathway is energetically favourable
some energy also converted to heat
describe the two ways that pyruvate is then used
Aerobic oxidation (oxygen available)
- pyruvate is converted to acetyl-CoA to be further metabolised in the citric acid cycle
- occurs in the mitochondria matrix
- pyruvate dehydrogenase reaction (so will be redox)
- multi enzyme complex with lots of cofactors/coenzymes
- net reaction is an oxidative decarboxylation (- delta G) (basically chopping a C off, adding CoA and the energy to do this comes from oxidising pyruvate
- CO2 released (decarboxylation; 3C to 2C)
- pyruvate is oxidised, energy captured in NADH and used to add Coenzyme A (CoA) to two-carbon chain
Anaerobic glycolysis (low oxygen)
- red blood cells, muscles in anaerobic conditions
- pyruvate goes to lactate (by lactate dehydrogenase)
- NADH goes to NAD+ so the energy is no longer stored in NADH
- low concentration of coenzymes in cells
- during aerobic oxidation coenzymes are oxidised (regenerated) in oxidative phosphorylation
Lactate formation allows for the regeneration of NAD+:
- lactate dehydrogenase reactions oxidised NAD
- sufficient NAD+ for the G-3-P dehydrogenase reaction
- glycolysis can continue to generate ATP even when low oxygen
describe how Coenzyme A (CoA) is another important enzyme in the pathways
- derived from pantothenic acid (vitamin B5)
- not a carrier of electrons (not reduced/oxidised)
Carries: acyl groups (2C to long C chains)
Two forms:
- free coenzyme A (CoASH)
- acyl group attached: Acyl-CoA (AcCoA)
CoASH (free)
- has a reactive SH- group on the end (called CoASH to show that that bit is not bound to anything)
- acyl group gets attached through the sulfur (which gives us Acyl-CoA)
