Carbohydrate Metabolism I: Glycolysis and Gluconeogenesis

Chapter 9: Carbohydrate Metabolism I: Glycolysis and Gluconeogenesis

6 min read Updated Apr 18, 2026
Read the entire chapter on one page Every section in order, with the sidebar tracking where you are as you scroll.
🎯 Diagnostic: Test Your Starting Level 18 questions (2 per section). No prior reading required - see what you already know.

Aim to answer every question before checking. Missed questions point you to the sections you need most.

1. (9.1) Catabolism refers to:
B. Catabolism = breakdown (exergonic, releases energy, often oxidative). Anabolism = building up (endergonic, uses ATP/NADPH, often reductive). Glycolysis, β-oxidation, and TCA are catabolic.
2. (9.1) ATP is considered the universal energy currency because:
D. ATP's phosphoanhydride bonds store moderate energy that can be coupled to endergonic reactions via phosphoryl transfer. The actual cellular ΔG is more negative than standard because [ATP] >> [ADP][Pi].
3. (9.2) The first step of glycolysis, catalyzed by hexokinase, is:
A. Hexokinase phosphorylates glucose → G6P, consuming the first ATP. This "traps" glucose in the cell (charged G6P can't cross membranes) and commits it to glycolysis or glycogen storage. In liver, glucokinase (a hexokinase IV isoform) does this job with a higher Km so it only activates after meals.
4. (9.2) Phosphofructokinase-1 (PFK-1) is considered the rate-limiting enzyme of glycolysis because:
C. PFK-1 is activated by AMP and F2,6BP (low-energy or hormonal signals), inhibited by ATP and citrate (high-energy signals). Controlling PFK-1 controls the whole pathway.
5. (9.3) The net yield of glycolysis per glucose is:
B. Invested: 2 ATP. Produced: 4 ATP + 2 NADH + 2 pyruvate. Net: 2 ATP + 2 NADH + 2 pyruvate. Glycolysis alone = small yield; the big ATP numbers come from feeding pyruvate into the TCA cycle and ETC.
6. (9.3) Substrate-level phosphorylation in glycolysis occurs at which enzymes?
D. Phosphoglycerate kinase transfers a phosphate from 1,3-BPG to ADP → ATP. Pyruvate kinase transfers a phosphate from PEP to ADP → ATP. Each glucose produces 2 × (1+1) = 4 ATP from substrate-level phosphorylation.
7. (9.4) Fructose-2,6-bisphosphate is a potent allosteric activator of:
C. F2,6BP is a regulatory molecule, not a pathway intermediate. Its level is controlled by the bifunctional enzyme PFK-2/FBPase-2, which is itself regulated by insulin and glucagon. Net effect: insulin raises F2,6BP → glycolysis on, gluconeogenesis off. Glucagon inverts this.
8. (9.4) Insulin promotes glycolysis by:
A. Insulin activates phosphatases that dephosphorylate PFK-2/FBPase-2. This favors its kinase activity, making F2,6BP, which activates PFK-1 and inhibits FBPase-1 - the fed-state switch that runs glycolysis and blocks gluconeogenesis simultaneously.
9. (9.5) Under anaerobic conditions in muscle, pyruvate is reduced to:
B. Lactate dehydrogenase converts pyruvate + NADH → lactate + NAD+. This recycles NAD+ back to glycolysis so it can keep making ATP without oxygen. Yeast do ethanol fermentation instead (pyruvate → acetaldehyde → ethanol).
10. (9.5) Under aerobic conditions, pyruvate is transported to mitochondria and converted to:
D. PDH is a huge multi-enzyme complex that uses 5 cofactors (TPP, lipoamide, CoA, FAD, NAD+) to oxidatively decarboxylate pyruvate. The acetyl-CoA feeds into the TCA cycle in Chapter 10.
11. (9.6) Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors. It occurs primarily in:
C. Liver is the main gluconeogenic organ; it maintains blood glucose between meals. The kidney contributes about 10% in fasting. Muscle cannot release free glucose (lacks glucose-6-phosphatase). Gluconeogenic precursors: lactate, glycerol, glucogenic amino acids.
12. (9.6) Gluconeogenesis differs from reversed glycolysis at which three "irreversible" steps?
A. Bypasses: (1) pyruvate → PEP via pyruvate carboxylase + PEPCK; (2) F1,6BP → F6P via fructose-1,6-bisphosphatase; (3) G6P → glucose via glucose-6-phosphatase (liver only). Each bypass uses energy - gluconeogenesis costs 6 high-energy phosphate bonds per glucose.
13. (9.7) Glycogen phosphorylase breaks down glycogen by:
B. Phosphorolysis uses Pi instead of H2O. Output: glucose-1-phosphate, which is converted to glucose-6-phosphate and enters glycolysis - bypassing the need for hexokinase's ATP. An energetic savings for the cell.
14. (9.7) Epinephrine and glucagon stimulate glycogen breakdown by:
D. Classic Sutherland cascade: hormone → Gαs → adenylyl cyclase → cAMP → PKA → phosphorylase kinase → glycogen phosphorylase (GPa form). The cascade amplifies: one hormone molecule triggers millions of glucose releases.
15. (9.8) The main purpose of the pentose phosphate pathway is to produce:
C. PPP makes NADPH (for fatty acid/cholesterol synthesis, for glutathione reduction) and R5P (for DNA/RNA). Operates in liver, adipose, erythrocytes, and rapidly dividing tissues. G6PD is the rate-limiting enzyme.
16. (9.8) G6PD deficiency causes hemolytic anemia because:
A. NADPH regenerates reduced glutathione, which neutralizes ROS. Without G6PD, oxidative stress (from fava beans, antimalarials, infections) overwhelms the defense, cross-links hemoglobin (Heinz bodies), and hemolysis follows.
17. (9.9) In the Cori cycle, lactate from exercising muscle is:
B. Cori cycle: muscle (net 2 ATP from glycolysis to lactate) sends lactate to the liver (spends 6 ATP to rebuild glucose). The cycle transfers the energy cost to the liver, sparing the muscle during heavy exertion.
18. (9.9) In the glucose-alanine cycle:
D. Alanine carries muscle's nitrogen waste to the liver safely (avoiding a spike of toxic free ammonia). Liver deaminates alanine back to pyruvate + glutamate, feeds NH3 into the urea cycle, uses pyruvate for gluconeogenesis.

Glycolysis breaks glucose into pyruvate, capturing a little energy along the way. It is the oldest and most universal energy pathway - every living cell has it. In this chapter we cover glycolysis, the fate of pyruvate, gluconeogenesis (glucose from pieces, in reverse), glycogen metabolism, and a handful of related carbohydrate pathways.

Why Glycolysis, and Where Does It Lead?

Glycolysis is step 1 of getting energy from glucose. By itself it produces only 2 ATP per glucose - not much. Its real value is in handing off pyruvate to the mitochondrion, where pyruvate dehydrogenase converts it to acetyl-CoA, and the citric acid cycle (also called the TCA cycle or Krebs cycle) oxidizes acetyl-CoA all the way to CO2. Each turn of the TCA cycle strips electrons as NADH and FADH2. Those electron carriers then donate their electrons to the electron transport chain (ETC), which uses the energy to pump protons and drive ATP synthase. So the pipeline is:

Glucose → glycolysis (cytoplasm) → pyruvate → PDH (mitochondrion) → acetyl-CoA → TCA cycle → NADH/FADH2 → ETC → proton gradient → ATP synthase → ATP.

This chapter handles glycolysis and its immediate neighbors. Chapter 10 picks up at pyruvate dehydrogenase and finishes the pipeline through the TCA cycle and ETC.

Glycolysis is Cracking a Hundred-Dollar Bill

Keep in mind that glycolysis invests 2 ATP upfront, then earns 4 ATP back plus 2 NADH. Net: 2 ATP and 2 NADH per glucose, plus 2 pyruvate for further processing. No oxygen required. It happens in the cytoplasm of every cell.

In This Chapter