Chapter 7 — Cellular Respiration & Fermentation

What is glycolysis?

The process of breaking down glucose (6C) into two pyruvates (3C) in the cytosol, producing ATP and NADH.

Where does glycolysis occur?

In the cytosol.

What controls glucose concentration?

• Substrate & energy availability

• Hormones

• Feedback inhibition

• Enzymatic control (glycogenesis, glycogenolysis)

How does Type 1 diabetes affect glucose regulation?

Not enough insulin

How does Type 2 diabetes affect glucose regulation?

Insulin resistance

What are the products of glycolysis?

• 2 ATP (net gain)

• 2 NADH + H⁺

• 2 Pyruvate

How many steps are in glycolysis and what are the two phases?

10 steps:

• Phase 1: Energy investment (5 reactions)

• Phase 2: Energy payoff (5 reactions)

What enzyme starts glycolysis?

Hexokinase — adds phosphate to glucose (irreversible).

Why is adding phosphate to glucose important?

It traps glucose in the cell and commits it to metabolism.

What are the three control points in glycolysis?

1. Hexokinase

2. Phosphofructokinase

3. Pyruvate kinase

What does phosphofructokinase do?

Regulates the rate of glycolysis; inhibited by ATP and citrate, activated by ADP and AMP.

What determines pyruvate’s fate?

Oxygen availability — aerobic → mitochondria, anaerobic → fermentation.

What happens if oxygen isn’t available?

Fermentation occurs (anaerobic process).

What are free radicals and how are they controlled?

Reactive oxygen species from metabolism; neutralized by antioxidants

What is fermentation?

Anaerobic process regenerating NAD⁺ to keep glycolysis going.

What are fermentation products?

• Yeast: Ethanol (2C) + CO₂ (1C)

• Muscle: Lactate (3C)

Why is NADH important in glycolysis?

It carries high-energy electrons to be used later in oxidative phosphorylation.

What reaction shows fermentation’s role?

Glucose + 2ADP + 2Pi + 2NAD⁺ → 2ATP + 2NADH + 2 pyruvate → lactate or ethanol + NAD⁺

What causes bread to rise?

CO₂ produced anaerobically by yeast during fermentation.

Who discovered the citric acid cycle?

Hans Krebs (1930s); won the Nobel Prize in 1953.

What is the concept of a metabolic cycle?

A series of reactions where certain molecules enter and others leave, regenerating the starting compound each turn.

Where does the citric acid cycle occur?

In the mitochondrial matrix.

What enters the citric acid cycle?

Acetyl-CoA (2C) combines with oxaloacetate (4C) → citrate (6C).

What happens during one turn of the cycle?

• 2 CO₂ released

• 3 NADH

• 1 FADH₂

• 1 ATP (via GTP)

• Oxaloacetate regenerated

What are the net products per acetyl group?

3 NADH, 1 FADH₂, 1 ATP, and 2 CO₂.

What are NADH and FADH₂ used for?

Carry high-energy electrons to the electron transport chain (ETC).

How is the citric acid cycle regulated?

• Controlled by substrate availability (acetyl-CoA, NAD⁺)

• Feedback inhibition by NADH and ATP

• Activated by NAD⁺ and ADP

Which enzymes regulate the Krebs cycle most?

Citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase.

What other role does the cycle play besides energy?

Provides intermediates for amino acid, nucleotide, and lipid synthesis.

What is oxidative phosphorylation?

Process where electrons from NADH/FADH₂ power ATP synthesis via the electron transport chain and chemiosmosis.

Where does oxidative phosphorylation occur?

Inner mitochondrial membrane.

What are the two parts of phosphorylation?

• Electron Transport Chain (ETC)

• Chemiosmosis (ATP synthesis)

What happens in the ETC?

Electrons pass through complexes I–IV, pumping protons into the intermembrane space.

What is the final electron acceptor in phosphorylation?

Oxygen (O₂), forming H₂O.

How is ATP made?

Protons flow back into the matrix through ATP synthase, driving ATP formation.

What is F₀ in ATP synthase?

Membrane section, rotates and moves protons

What is F₁ in ATP synthase?

Matrix section, synthesizes ATP

What is a proton gradient?

High H⁺ concentration in the intermembrane space; drives ATP production.

What happens if the ETC is blocked?

ATP production stops → cell death (no energy).

Order of phosphorylation?

• Complex I (NADH dehydrogenase):

  • Electrons: NADH → Complex I → Ubiquinone (CoQ)

  • Protons: pumped from matrix → intermembrane space

  Complex II (Succinate dehydrogenase):

  • Electrons: FADH₂ → Complex II → Ubiquinone (CoQ)

  • Protons: not pumped

  Ubiquinone (CoQ):

  • Electrons: carries from Complex I & II → Complex III

  • Protons: not pumped

  Complex III (Cytochrome bc₁ complex):

  • Electrons: CoQ → Complex III → Cytochrome c

  • Protons: pumped from matrix → intermembrane space

  Cytochrome c:

  • Electrons: Complex III → Complex IV

  • Protons: not pumped

  Complex IV (Cytochrome c oxidase):

  • Electrons: Cytochrome c → Complex IV → O₂ → H₂O

  • Protons: pumped from matrix → intermembrane space

  Proton gradient:

  • Intermembrane space: high H⁺ concentration

  • Matrix: low H⁺ concentration

Complex I

Rotenone, Amytal, Metformin

Blocks electron transfer to CoQ

Complex II

Malonate

Inhibits succinate dehydrogenase

Complex III

Antimycin A

Blocks cytochrome b → c

Complex IV

Cyanide, CO, Azide, H₂S

Prevents O₂ from accepting electrons

What does arsenic do?

Inhibits pyruvate dehydrogenase → prevents Acetyl-CoA formation.

What vitamins are required for oxidative phosphorylation?

B₃ (Niacin)

B₂ (Riboflavin)

B₅ (Pantothenic acid)

Coenzyme of B₃ (Niacin)

NAD⁺

Forms NADH

Coenzyme of B₂ (Riboflavin) and function

FAD, FMN

Accept electrons (Complex II)

Coenzyme of B₅ (Pantothenic acid) and function

CoA

Forms Acetyl-CoA

How are carbohydrate, protein, and fat metabolism interconnected?

They share enzymes and pathways; breakdown products enter glycolysis or the citric acid cycle.

How do proteins enter respiration?

Broken into amino acids → modified to enter glycolysis or the citric acid cycle.

How do fats enter respiration?

• Glycerol → G3P (glycolysis)

• Fatty acids → acetyl-CoA (citric acid cycle)

What is an advantage of shared pathways?

Efficiency — cells use the same enzymes for multiple types of molecules.

What happens during the ketogenic (keto) diet?

Body shifts to burning fats → produces ketones as fuel instead of glucose.

What are possible long-term effects of keto adaptation?

Body becomes more efficient at using ketones; basal metabolic rate may decrease.