bioch lec 9- glycolysis and PDH
What does glycolysis convert glucose into, and how many ATP/NADH does it directly generate? (3 numbers)
It converts 1 glucose → 2 pyruvate, producing 2 net ATP and 2 NADH directly.
What distinguishes glycolysis as ancient and conserved? (1 concept)
It is an anaerobic ATP-generating pathway that functions in almost all cells and predates oxygen-based metabolism.
Where does glycolysis occur and how many enzyme-catalyzed steps does it include? (2 facts)
It occurs in the cytosol and includes 10 enzyme-catalyzed reactions.
What are the two stages of glycolysis and what happens in each? (2 definitions)
Energy investment: ATP is consumed to activate glucose.
Energy payout: ATP and NADH are produced from triose intermediates.
Which glycolysis steps consume ATP, and which generate ATP? (4 steps)
Consume ATP: Steps 1 & 3 (hexokinase, PFK-1).
Generate ATP: Steps 7 & 10 (phosphoglycerate kinase, pyruvate kinase)
Which steps of glycolysis are substrate-level phosphorylations? (2 steps)
Steps 7 (1,3-BPG → 3-PG) and 10 (PEP → pyruvate).
Which step is the oxidation step, and what cofactor is produced? (1 step + product)
Step 6 (GAPDH), producing NADH.
Which three steps are irreversible in glycolysis? (3 steps)
Steps 1 (hexokinase), 3 (PFK-1), and 10 (pyruvate kinase).
Which enzyme is the rate-limiting step of glycolysis? (1 enzyme)
Phosphofructokinase-1 (PFK-1).
What are four key features of the hexokinase reaction? (4 features)
Irreversible, exergonic (ΔG ≪ 0), ATP-coupled phosphate transfer, inhibited by G6P (product inhibition).
Why is glucose → fructose conversion an isomerization? (1 explanation)
It converts an aldohexose → ketohexose, shifting the carbonyl between C1 and C2.
What four features characterize the PFK-1 reaction? (4 features)
Irreversible, ATP-dependent phosphorylation, rate-limiting, highly regulated allosterically.
Into what two molecules does aldolase split F-1,6-BP? (2 products)
GAP and DHAP, which are structural isomers
Why must DHAP be converted to GAP? (1 reason)
Only GAP continues down the payoff phase, so DHAP is isomerized to maintain two triose molecules.
How many total GAP molecules are generated per glucose? (1 number)
Two, and all downstream reactions occur twice per glucose.
Why is 1,3-BPG a high-energy intermediate? (1 chemical reason)
It contains an acyl phosphate, whose hydrolysis yields highly stabilized resonance products.
What are the two “energy capture” steps of glycolysis? (2 steps + products)
Step 6: NADH generated; Step 7: ATP generated.
What type of reaction forms PEP? (1 word)
A dehydration reaction (2-PG → PEP).
Why does the pyruvate kinase step release large free energy? (1 explanation)
Conversion from enolpyruvate → pyruvate is highly favorable (ΔG ≪ 0).
How many ATP does pyruvate kinase generate per glucose? (1 number)
2 ATP per glucose (one per PEP).
What is the net ATP from glycolysis? (1 value)
2 net ATP. (4 generated − 2 consumed).
What are the four major mechanisms that regulate glycolysis flux? (4 mechanisms)
Substrate availability, enzyme activity regulation, enzyme amount, compartmentation.
What three enzymes are the key regulatory points of glycolysis? (3 enzymes)
Hexokinase, PFK-1, pyruvate kinase.
What inhibits hexokinase? (1 inhibitor)
G6P (product inhibition).
How do AMP/ADP and PEP regulate PFK-1? (2 opposite effects)
AMP/ADP activate PFK-1; high PEP inhibits via feedback inhibition.
What two allosteric regulators affect pyruvate kinase? (2 regulators)
Activated by F-1,6-BP (feed-forward) and inhibited by ATP.
Why must irreversible steps be synchronously regulated? (1 reason)
To maintain steady-state concentrations of intermediates and prevent futile flux.
Which glycolysis steps are considered “ATP investment”? (2 steps)
Steps 1 & 3
Which two steps are dehydration and isomerization in the payoff phase? (2 steps)
Step 8: isomerization (3-PG ⇌ 2-PG).
Step 9: dehydration (2-PG → PEP).
Why does glycogen breakdown increase the net ATP yield of glycolysis? (1 reason)
Because G-1-P → G-6-P requires no ATP, saving one ATP compared to glucose entry.
Why is anaerobic pyruvate reduction required? (1 reason)
To regenerate NAD⁺ so glycolysis can continue without oxidative phosphorylation.
What are the two anaerobic fates of pyruvate? (2 fates)
Lactate (muscle, RBCs) and ethanol (yeast)
Why is lactate not an acid, and where is it exported? (2 facts)
Lactate exists as a deprotonated anion, and it is exported via a specific membrane transporter.
What benefit does lactate export provide during intense exercise? (1 benefit)
It removes accumulated H⁺ from ATP hydrolysis, preventing acid damage to muscle fibers.
How is lactate used as a fuel in cardiac tissue? (1 pathway)
It is converted to pyruvate → acetyl-CoA → CAC for oxidation.
Where does the PDH reaction occur, and what transporter is required? (2 facts)
PDH occurs in the mitochondrial matrix, requiring pyruvate translocase co-transporting H⁺
What three processes make up the PDH reaction? (3 processes)
Oxidation, decarboxylation, and transacetylation
Oxidation, decarboxylation, and transacetylation
Pyruvate + CoA + NAD⁺ → Acetyl-CoA + NADH + CO₂.
Why is PDH irreversible and highly regulated? (1 reason)
Because acetyl-CoA cannot be converted back to glucose in mammals.
What are the three catalytic enzymes and three required cofactors of PDH? (6 items)
Enzymes: E1, E2, E3 (decarboxylation, transfer, oxidation).
Cofactors: NAD⁺, FAD, CoA (plus two more: TPP and lipoamide).
What are two advantages of PDH being a multienzyme complex? (2 advantages)
It speeds reactions and limits side reactions, allowing coordinated control.
What three molecules regulate PDH via allostery and substrate/product effects? (3 regulators)
NADH (inhibits), acetyl-CoA (inhibits), NAD⁺/HS-CoA (activate)
How is PDH regulated by phosphorylation? (2 statements)
Kinase phosphorylates and inactivates PDH; phosphatase dephosphorylates and activates it
What role does Ca²⁺ play in PDH regulation in muscle? (1 role)
Ca²⁺ activates PDH phosphatase, turning PDH on during muscle contraction