Cellular Respiration – Glucose, Proteins & Fats

Overview of Cellular Respiration and Fuel Flexibility

• Cellular respiration = umbrella term for catabolic pathways that harvest the chemical energy of food molecules and convert it to the chemical energy stored in \text{ATP}.

• Three principal nutrient classes feed into the pathway:

  • Carbohydrates (reference fuel = glucose)

  • Proteins

  • Fats (triacylglycerols)

• All three converge on the same aerobic machinery—Krebs (citric-acid) cycle + Electron Transport Chain (ETC)—but differ in preprocessing steps, entry points, ATP yield, and waste products.

Glucose Metabolism (Reference Pathway)

• Sequential pathway:

  • Glycolysis (cytosol)

  • Link (pyruvate → acetyl-CoA)

  • Krebs cycle (matrix)

  • ETC + oxidative phosphorylation (inner mitochondrial membrane)

• Net ATP yield per glucose: \approx 36\text{–}38\;\text{ATP} (variation due to shuttle systems & membrane potential cost).

• Waste products: \text{CO}2 (decarboxylations) and \text{H}2\text{O} (final reduction of \text{O}_2).

• Significance: fastest, most direct energy source; brain and red blood cells are heavily glucose-dependent.

Protein Metabolism

• Proteins → amino acids via proteolysis.

• Deamination (mainly in liver): removes amino group, producing ammonia → converted to urea (less toxic, excreted via kidneys).

• Carbon skeleton fate depends on side-chain structure:

  • Can become pyruvate, acetyl-CoA, or one of several Krebs intermediates (α-ketoglutarate, succinyl-CoA, fumarate, oxaloacetate).

• ATP yield = variable; higher when entry is earlier (e.g., as pyruvate) and lower when later (e.g., fumarate) due to fewer oxidation steps remaining.

• Waste: \text{CO}2, \text{H}2\text{O}, and urea [(\text{NH}2)2\text{CO}].

• Contextual note: protein catabolism generally increases in prolonged fasting or intense exercise when glycogen/lipid stores are depleted; excessive reliance can damage muscle mass.

Fat Metabolism

• Triacylglycerol → glycerol + 3 fatty-acid chains.

• Glycerol (a 3-carbon molecule): phosphorylated → glyceraldehyde-3-phosphate → enters glycolysis.

• Fatty acids: sequentially cleaved in β-oxidation (mitochondrial matrix) → multiple acetyl-CoA molecules + reduced coenzymes \text{NADH} and \text{FADH}_2.

  • Example: palmitic acid (16 C) → 8 acetyl-CoA; total ATP yield \approx 129\;\text{ATP}.

• High energy density: more C–H bonds and is largely anhydrous storage; therefore, preferred for long-term energy reserves.

• Waste: \text{CO}2 + \text{H}2\text{O} (no nitrogen).

Comparative Summary of Fuels

• Entry pathways & preprocessing:

  • Glucose: none → glycolysis.

  • Proteins: deamination → various Krebs entry points.

  • Fats: β-oxidation → acetyl-CoA (fatty acids) or glycolytic intermediate (glycerol).

• Relative ATP yields:

  • Glucose: 36\text{–}38.

  • Proteins: dependent; can be similar to or less than glucose.

  • Fats: very high; long-chain FA >100\;\text{ATP}.

• Waste products:

  • Glucose & fats: CO2, H2O.

  • Proteins: CO2, H2O + urea.

Key Take-Home Points

• Glucose is metabolically most accessible and usually prioritized, especially under standard dietary conditions.

• Fats provide the greatest ATP per molecule but require oxygen and time for β-oxidation; dominate during rest, low-intensity exercise, or prolonged fasting.

• Proteins serve as an emergency fuel; their metabolism is limited by toxic nitrogen handling and the structural/functional necessity of proteins.

• All three fuels intersect at the Krebs cycle and rely on the ETC; thus, adequate oxygen availability remains the ultimate bottleneck for maximal ATP production.