Chapter Review
Bioenergetics
Cellular Respiration of Carbohydrates, Fats and Proteins
Cellular Respiration Overview
Step-by-step breakdown of organic molecules within cells to harvest usable energy as ATP. Glucose, fats, and proteins all feed into the same central pathways — glycolysis, Krebs cycle, and the electron transport chain.
Key Points
- •Four aerobic stages: Glycolysis (cytosol), pyruvate oxidation (mitochondrial matrix), Krebs cycle (matrix), ETC (inner mitochondrial membrane)
- •Aerobic respiration completely oxidises glucose to $CO_2$ and $H_2O$, yielding approximately 36–38 ATP
- •Anaerobic fermentation yields only 2 ATP per glucose — approximately 2% of available energy
- •Mitochondria are the primary aerobic respiration sites; cristae house ETC proteins, matrix contains Krebs enzymes
- •Fats and proteins also enter respiration at specific entry points — glucose is not the only fuel
Glycolysis
Ten-enzyme pathway in the cytosol that splits one glucose (6C) into two pyruvate molecules (3C). Does not require oxygen. Net yield: 2 ATP, 2 NADH.
Key Points
- •Preparatory phase: 2 ATP consumed to form fructose 1,6-bisphosphate, which is cleaved into G3P and DHAP
- •Payoff phase: Each G3P is oxidised to produce NADH and ATP via substrate-level phosphorylation; 4 ATP produced
- •Net yield: 2 ATP + 2 NADH + 2 pyruvate (4 produced − 2 consumed)
- •G3P is the key 3-carbon intermediate; glycerol from fats enters glycolysis here as DHAP
- •In absence of oxygen, pyruvate undergoes fermentation instead of entering the Krebs cycle
Formula
$$C_6H_{12}O_6 + 2NAD^+ + 2ADP + 2P_i \longrightarrow 2C_3H_4O_3 + 2NADH + 2H^+ + 2ATP$$
Pyruvate Oxidation (Link Reaction)
Pyruvate is transported into the mitochondrial matrix and oxidatively decarboxylated to acetyl-CoA. Each pyruvate loses one carbon as $CO_2$ and generates one NADH.
Key Points
- •Catalyst: Pyruvate dehydrogenase complex requires 5 coenzymes — $NAD^+$, CoA, FAD, lipoic acid, thiamine ($B_1$)
- •Each pyruvate (3C) → acetyl-CoA (2C) + $CO_2$ + NADH
- •Per glucose: 2 pyruvate → 2 acetyl-CoA + 2 $CO_2$ + 2 NADH
- •This is an irreversible step — once pyruvate becomes acetyl-CoA, it cannot return to glycolysis
- •Links glycolysis to the Krebs cycle
Formula
$$C_3H_4O_3 + NAD^+ + CoA \longrightarrow CH_3CO \sim SCoA + CO_2 + NADH + H^+$$
Krebs Cycle
Eight-enzyme cyclic pathway in the mitochondrial matrix. Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C); two carbons are released as $CO_2$ and oxaloacetate is regenerated. Each turn yields 1 ATP, 3 NADH, 1 $FADH_2$.
Key Points
- •Intermediates (in order): Citrate → isocitrate → $\alpha$-ketoglutarate → succinyl-CoA → succinate → fumarate → malate → oxaloacetate
- •Oxaloacetate is both the starting and ending molecule — never consumed
- •Two $CO_2$ released per turn represent carbons from acetyl-CoA, not oxaloacetate
- •$FADH_2$ is produced at succinate → fumarate step by succinate dehydrogenase
- •Per glucose (2 turns): 2 ATP + 6 NADH + 2 $FADH_2$
Electron Transport Chain and Oxidative Phosphorylation
NADH and $FADH_2$ donate electrons to carrier proteins (coenzyme Q, cytochromes) in the inner mitochondrial membrane, ultimately reducing $O_2$ to $H_2O$. The energy released pumps protons, creating a gradient that drives ATP synthase.
Key Points
- •Carriers (in order): NADH → Complex I → CoQ → Complex III (cytochrome b) → cytochrome c → Complex IV (cytochrome a/a₃) → $O_2$
- •NADH enters at Complex I and yields approximately 3 ATP; $FADH_2$ enters at CoQ (bypasses Complex I) and yields approximately 2 ATP
- •Chemiosmosis: Proton gradient across inner membrane drives ATP synthase to phosphorylate ADP
- •Cytochromes undergo reversible $Fe^{2+}/Fe^{3+}$ valency changes to transfer electrons
- •ETC produces approximately 34 ATP from 10 NADH and 2 $FADH_2$ — the bulk of total ATP
Formula
$$NADH + H^+ + 3ADP + 3P_i + \frac{1}{2}O_2 \longrightarrow NAD^+ + H_2O + 3ATP$$
Anaerobic Respiration (Fermentation)
When oxygen is unavailable, pyruvate undergoes fermentation to regenerate $NAD^+$, allowing glycolysis to continue. Yields only 2 ATP per glucose.
Key Points
- •Purpose: Regenerate $NAD^+$ (NOT to produce more ATP) so glycolysis can continue
- •Lactic acid fermentation: Pyruvate → lactate (via lactate dehydrogenase) — occurs in muscle cells during intense exercise
- •Alcoholic fermentation: Pyruvate → acetaldehyde (+$CO_2$) → ethanol — occurs in yeast and some plant cells
- •Lactate accumulation is temporary — transported to liver and converted back to pyruvate (Cori cycle)
- •Products still contain most of glucose's energy; only complete oxidation (Krebs + ETC) extracts the full amount
Respiration of Fats
Triglycerides are hydrolysed into glycerol and fatty acids. Glycerol enters glycolysis as G3P; fatty acids undergo beta-oxidation to produce acetyl-CoA units that enter the Krebs cycle.
Key Points
- •Lipolysis: Triglyceride → 1 glycerol + 3 fatty acids (by lipase enzymes)
- •Glycerol path: Glycerol → glycerol-3-phosphate (−1 ATP) → DHAP → G3P → glycolysis payoff phase
- •Beta-oxidation: Each cycle removes 2 carbons as acetyl-CoA, producing 1 NADH + 1 $FADH_2$
- •Fatty acid activation (attachment to CoA) costs 2 ATP equivalents
- •One palmitic acid (C₁₆) yields approximately 129 ATP — far more than glucose (38 ATP)
- •Fatty acids cannot be converted to glucose in animals (pyruvate dehydrogenase is irreversible)
Formula
$$\text{Palmitic acid (C}_{16}) \longrightarrow 8\text{ Acetyl-CoA} + 7\text{NADH} + 7\text{FADH}_2$$
Respiration of Proteins
Proteins are used as fuel during prolonged fasting. Amino acids are deaminated (amino group removed as urea), and the carbon skeletons enter glycolysis or Krebs cycle at various points.
Key Points
- •Deamination: Amino group ($NH_2$) removed by transaminases or oxidative deamination; nitrogen excreted as urea (ornithine cycle)
- •Glucogenic amino acids: Carbon skeletons convert to pyruvate or Krebs intermediates → can produce glucose via gluconeogenesis (e.g., alanine → pyruvate)
- •Ketogenic amino acids: Degrade to acetyl-CoA — cannot be converted to glucose in animals. Leucine and lysine are purely ketogenic
- •Both: Isoleucine, phenylalanine, tyrosine, threonine, tryptophan produce both glucogenic and ketogenic fragments
- •Ketone bodies: Excess acetyl-CoA during fasting converted to acetone, acetoacetate, $\beta$-hydroxybutyrate — alternative brain fuel
Correlating the Three Nutrient Pathways
Carbohydrates, fats, and proteins all converge on the same central metabolic core (Krebs cycle + ETC), just entering at different points. Cells preferentially use glucose first, then fats, then proteins as a last resort.
Key Points
- •Glucose: Glycolysis → pyruvate → acetyl-CoA → Krebs cycle → ETC
- •Glycerol: DHAP/G3P → glycolysis → pyruvate → acetyl-CoA → Krebs cycle → ETC
- •Fatty acids: Beta-oxidation → acetyl-CoA → Krebs cycle → ETC
- •Amino acids: Pyruvate, acetyl-CoA, or various Krebs intermediates → ETC
- •Energy per gram: Fats (~9 kcal/g) > proteins (~4 kcal/g) ≈ carbohydrates (~4 kcal/g)
- •Glycerol can be converted to glucose; fatty acids cannot; glucogenic amino acids can
Formulas
Glycolysis Net Equation
Net production per glucose in the cytosol: 2 pyruvate, 2 net ATP, 2 NADH
Formula
$$C_6H_{12}O_6 + 2NAD^+ + 2ADP + 2P_i \longrightarrow 2C_3H_4O_3 + 2NADH + 2H^+ + 2ATP$$
Total ATP per Glucose
2 (glycolysis net) + 2 (Krebs substrate-level) + 30 (10 NADH × 3) + 4 (2 FADH₂ × 2) = 38 ATP
Formula
$$2 + 2 + 30 + 4 = 38$$
Pyruvate Oxidation
Each pyruvate decarboxylated and oxidised to acetyl-CoA, releasing CO₂ and producing NADH
Formula
$$C_3H_4O_3 + NAD^+ + CoA \longrightarrow CH_3CO \sim SCoA + CO_2 + NADH + H^+$$
Beta-Oxidation Cycle Count
For n-carbon fatty acid: cycles = n/2 − 1, acetyl-CoA produced = n/2
Formula
$$\text{Cycles} = \frac{n}{2} - 1, \quad \text{Acetyl-CoA} = \frac{n}{2}$$
ATP per Acetyl-CoA (Krebs + ETC)
Each acetyl-CoA through one Krebs turn yields 12 ATP total
Formula
$$3 \times 3 + 1 \times 2 + 1 = 12$$
Oxidative Phosphorylation (per NADH)
Each NADH yields 3 ATP through ETC; each FADH₂ yields 2 ATP (enters at CoQ)
Formula
$$NADH + H^+ + 3ADP + 3P_i + \frac{1}{2}O_2 \longrightarrow NAD^+ + H_2O + 3ATP$$
Palmitic Acid Total ATP
C₁₆: 8 acetyl-CoA × 12 + 7 NADH × 3 + 7 FADH₂ × 2 − 2 = 129 ATP
Formula
$$8(12) + 7(3) + 7(2) - 2 = 129$$