Glycolysis & Citric Acid Cycle Flashcards
(26 cards)
What is aerobic catabolism?
- Free energy is obtained from the oxidation of carbon compounds in the presence of oxygen
- Electrons are transferred from the carbon compound to oxygen ultimate electron acceptor to form H2O
- Carbon atoms are converted to CO2 which is released as a waste product
- Oxidation is a multistep process = electrons are transferred in some reactions in small numbers
What is an oxidising agent?
Accepts electrons and is reduced itself
E.g. NAD+ + H+ + 2e- —> NADH
What is a reducing agent?
Loses electrons and is oxidised itself
E.g. NADPH —> NADP+ + H+ + 2e-
Role of NADH
- NADH is oxidised later by the respiratory electron-transport chain
- Oxidation of NADH by oxygen has ∆G = -220 kJ mol-1
- This energy is used to produce ATP from ADP and Pi
NAD+ vs NADP+
- NADP+ has an extra PO4 group which is involved in enzyme recognition
- NAD+ is used in catabolic pathways as an oxidising agent
- NADPH is used in anabolic pathways as a reducing agent
What are Flavin redox cofactors
FAD = a dinucleotide
FMN = a mononucleotide
Oxidation of flavin molecules
Step 1 —> oxidised form (Quinone) = FAD/FMN converted into the semi-reduced form (semiquinone) = FADH+/FMNH+ (radicals)
Step 2 —> from semiquinone to the reduced form (hydroquinone) = FADH2/FMNH2
What is glycolysis?
Converts 1 glucose to 2 pyruvate molecules
Net reaction of glycolysis
Produces
- 2x pyruvate molecules
- 2x ATP
- 2x NAD+ reduced to NADH
- 4x electrons from glucose are transferred to NAD+
Further metabolism of pyruvate
- Aerobic conditions = oxidised to Acetyl CoA
- Anaerobic conditions = converted to ethanol or lactate
Lactic fermentation
- conversion of pyruvate into lactate by lactate dehydrogenase
- done by several microorganisms
- and in cells of higher organisms in the absence of oxygen
- and in erythrocytes
What 3 reactions have a large ∆G in glycolysis?
- Glucose + ATP —> Glucose-6-P + ADP has a ∆G of -33 kJ mol-1
- Fructose-6-P + ATP —> Fructose-1,6-bisP + ADP has ∆G of -22 kJ mol-1
- Phosphoenolpyruvate + ADP —> Pyruvate + ATP has ∆G of -17 kJ mol-1
All involve ATP and ADP and the reactions are irreversible
What do irreversible reactions serve as in the glycolysis pathway?
‘Dams’ that are points of regulation of the pathway and control the rate pf glycolysis
Basic concepts of metabolic regulation
- metabolites in the same pathway can have feedback inhibition or feed-forward activation
- metabolites from outside the pathway can have allosteric regulation or metabolic & hormonal regulation
Regulation by hexokinase
- G6P inhibits hexokinase
- Product inhibition = a form of feedback inhibition
- G6P levels increase when glycolysis is inhibited downstream
- Inhibition of hexokinase prevents the accumulation of G6P
- In the liver, a separate enzyme called glucokinase catalyses the same reaction and is not inhibited by G6P
Regulation by phosphofructokinase
Fructose-6-P + ATP —> Fructose-1,6-bisP + ADP
- 3rd step is irreversible = rate limiting
- Phosphofructokinase-1 (PFP1) is the most important regulatory enzyme in glycolysis
- It inhibits by ATP
- PFK2 in the liver
- It is an allosteric enzyme
- ATP and citrate (in liver) are inhibitors
- AMP and fructose-2,6-bisP (in liver) are activators
Role of AMP
- relieves ATP inhibition of PFK1
- ATP build up indicates no need for more energy = PFK1 inhibition
- sufficient ATP levels = glycolysis is inactivated
- low ATP/AMP ratio indicates energy is needed = PFK1 activation
Other regulators
- Fructose-2,6-biphosphate is the most important activator for PFK1 in eukaryotes = controls glycolysis in liver
- High levels of citrate are inhibitory of PFK1
- High H+ concentrations also inhibit PFK1
Regulation by pyruvate kinase
- When high levels of ATP, feedback inhibition occurs
- When high levels of fructose-1,6-biphosphate, feed-forward activation occurs
- Covalent modification = phosphorylation
Pyruvate dehydrogenase complex (PDC)
Consist of 3 enzymes
- 24x E1 —> removes CO2
- 24x E2 —> transfer of acetyl group to Acetyl CoA
- 12x E3 —> cofactor regeneration
In eukaryotes it is located in the mitochondrial matrix
First stage of the citric acid cycle
- 2 carbon atoms (acetyl coA) enter the cycle
- 2 different carbon atoms are oxidised
- 2 molecules of carbon dioxide are released
- 2 molecules of NAD+ are reduced to NADH
- Succinyl-CoA is formed (energy rich thioester)
Second stage of citric acid cycle
- Succinyl-CoA is hydrolysed
- Succinate is oxidised in three steps to oxaloacetate
- One molecule of GTP or ATP is formed
- One CH2 group is oxidised to a C=O group
- One molecule of FAD is reduced to FADH2
- One molecule of NAD+ is reduced to NADH
Main parts of the citric acid cycle
For each acetyl coA that enters the cycle
- two molecules of CO2 are released
- coenzymes NAD+ (x3) and FAD (x1) are reduced to NADH and FADH2
- one GDP/ADP is phosphorylated to GTP/ATP
- initial molecule (oxaloacetate) is reformed
- carbon atoms entering the cycle are not lost in the first turn of the cycle
