BIOENERGETIC AND CHEMICAL FOUNDATION

Biochemical energetics is the study of how energy is produced, stored, and utilized within a biological system. Cells require energy to perform various functions, including metabolism, transport, movement, and biosynthesis.

• Energy is essential for:
  • Biosynthesis (formation of macromolecules like proteins, nucleic acids, and lipids).
  • Active transport (movement of molecules against concentration gradients).
  • Mechanical work (muscle contraction, cell movement).
  • Cell signaling (transmission of signals via phosphorylation).

The primary source of energy in the cell is Adenosine Triphosphate (ATP), which acts as an energy currency.

2. Energy Sources in the Cell

Cells obtain energy from three primary macronutrients:

1. Carbohydrates
   • Primary energy source.
   • Glucose undergoes glycolysis and oxidative phosphorylation to produce ATP.
2. Lipids (Fats)
   • Stored in adipose tissue and broken down into fatty acids.
   • Fatty acids undergo β-oxidation to produce ATP.
3. Proteins
   • Used as an energy source in extreme conditions (starvation).
   • Amino acids are deaminated and converted into metabolic intermediates.

3. ATP: The Universal Energy Currency

Structure of ATP

ATP consists of:

• Adenine (a nitrogenous base).
• Ribose (a five-carbon sugar).
• Three phosphate groups (linked by high-energy bonds).

ATP Hydrolysis

• ATP → ADP + Pi (Inorganic phosphate) + Energy (~7.3 kcal/mol)
• The energy released is used for cellular activities.
• ATP can be regenerated from ADP by phosphorylation.

4. Cellular Energy-Generating Pathways

Cells use different metabolic pathways to produce ATP. The primary pathways include glycolysis, the Krebs cycle, and the electron transport chain (ETC).

A. Glycolysis (Cytoplasm)

• The first step in cellular respiration.
  
• Occurs in the cytoplasm of all cells.
  
• Anaerobic process (does not require oxygen).
  
• Breaks down glucose (C₆H₁₂O₆) into 2 pyruvate molecules.
  
• Produces 2 ATP and 2 NADH per glucose molecule.
  
  Key Reactions:
  
  1. Glucose → Glucose-6-phosphate (via hexokinase, using ATP).
  2. Fructose-6-phosphate → Fructose-1,6-bisphosphate (via phosphofructokinase, using ATP).
  3. G3P (Glyceraldehyde-3-phosphate) is oxidized → produces NADH & ATP.
  4. End product: Pyruvate, which enters the mitochondria.

B. Krebs Cycle (Citric Acid Cycle or TCA Cycle) – Mitochondrial Matrix

• Pyruvate from glycolysis is converted into Acetyl-CoA before entering the cycle.
  
• Takes place in the mitochondrial matrix.
  
• Aerobic process (requires oxygen).
  
• Generates energy-rich molecules (NADH and FADH₂) to be used in ETC.
  
  Net Yield per Acetyl-CoA:
  
  • 3 NADH (electron carriers).
  • 1 FADH₂.
  • 1 ATP (or GTP).
  • 2 CO₂ (waste product).
• Since each glucose generates 2 Acetyl-CoA molecules, the total yield is doubled.

C. Electron Transport Chain (ETC) & Oxidative Phosphorylation – Inner Mitochondrial Membrane

• The final step of aerobic respiration.
• Takes place in the inner mitochondrial membrane.
• NADH and FADH₂ donate electrons to the ETC.
• Electrons pass through protein complexes, pumping protons (H⁺) into the intermembrane space.
• This creates a proton gradient, which drives ATP synthesis via ATP synthase.
• Oxygen (O₂) is the final electron acceptor, forming water (H₂O).

 Net ATP Yield:

• 1 NADH → 3 ATP.
• 1 FADH₂ → 2 ATP.
• Total: ~34 ATP per glucose molecule.

5. Anaerobic Respiration & Fermentation

When oxygen is unavailable, cells use anaerobic pathways to generate ATP.

A. Lactic Acid Fermentation (in animals & bacteria)

• Pyruvate is converted into lactic acid to regenerate NAD⁺.
• Occurs in muscle cells during intense activity.
• Produces only 2 ATP per glucose.

B. Alcoholic Fermentation (in yeast & some bacteria)

• Pyruvate is converted into ethanol and CO₂.
• Used in brewing and baking industries.
• Produces 2 ATP per glucose.

6. Alternative Energy Sources

A. Fatty Acid Oxidation (Beta-Oxidation)

• Occurs in the mitochondria.
• Fatty acids are broken down into Acetyl-CoA, which enters the Krebs cycle.
• Yields more ATP than glucose metabolism.

B. Protein Catabolism

• Proteins are broken down into amino acids.
• Amino acids undergo deamination (removal of the amino group).
• The remaining carbon skeleton enters the Krebs cycle.
• Used during starvation when carbohydrate and fat stores are low.

7. Regulation of Cellular Energy Metabolism

Cells regulate energy production based on demand.

A. Allosteric Regulation

• Enzymes in metabolic pathways are regulated by ATP levels.
• Example: Phosphofructokinase (PFK) in glycolysis is inhibited by ATP.

B. Hormonal Regulation

• Insulin (high blood glucose) → Stimulates glucose uptake & glycolysis.
• Glucagon (low blood glucose) → Stimulates gluconeogenesis & fatty acid oxidation.

C. Feedback Inhibition

• When ATP levels are high, ATP synthesis slows down.
• Example: ATP inhibits key enzymes in glycolysis and the Krebs cycle.

• Biochemical energetics focuses on how energy is produced and used in cells.
• ATP is the main energy carrier, generated via glycolysis, Krebs cycle, and ETC.
• Aerobic respiration (with O₂) produces ~38 ATP per glucose.
• Anaerobic respiration (without O₂) produces only 2 ATP per glucose.
• Cells also use fats and proteins for energy when needed.
• Metabolism is tightly regulated to ensure energy efficiency.

Applications of Biochemical Energetics

• Medical Science: Understanding metabolic disorders (e.g., diabetes, mitochondrial diseases).
• Biotechnology: Engineering microbes for biofuel production.
• Exercise Physiology: Enhancing athletic performance via metabolic optimization.

MCQ

1. Basic Concepts of Bioenergetics

1. What is the primary energy currency of the cell?
   a) Glucose
   b) NADH
   c) ATP ✅
   d) FADH₂
2. Which of the following is NOT a function that requires energy in cells?
   a) Biosynthesis
   b) Diffusion ✅
   c) Active transport
   d) Mechanical work
3. ATP consists of:
   a) Adenine, ribose, and three phosphate groups ✅
   b) Guanine, deoxyribose, and two phosphate groups
   c) Thymine, ribose, and three phosphate groups
   d) Uracil, ribose, and three phosphate groups
4. The high-energy bonds in ATP are located between:
   a) Adenine and ribose
   b) Ribose and phosphate groups
   c) Phosphate groups ✅
   d) Nitrogenous base and ribose
5. Which process regenerates ATP from ADP?
   a) Glycolysis
   b) Phosphorylation ✅
   c) Hydrolysis
   d) Fermentation

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2. Energy Sources in Cells

6. Which macronutrient is the primary source of energy?
   a) Proteins
   b) Lipids
   c) Carbohydrates ✅
   d) Vitamins
7. When carbohydrates are unavailable, cells prefer to use:
   a) Proteins
   b) Lipids ✅
   c) Nucleic acids
   d) Vitamins
8. The breakdown of fatty acids for energy occurs through:
   a) Glycolysis
   b) Beta-oxidation ✅
   c) Fermentation
   d) Transamination
9. In extreme starvation, cells use _______ for energy.
   a) Only lipids
   b) Only carbohydrates
   c) Proteins ✅
   d) Nucleotides
10. What is the first step in glucose metabolism?
    a) Electron transport chain
    b) Glycolysis ✅
    c) Krebs cycle
    d) Beta-oxidation

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3. Glycolysis

11. Where does glycolysis occur?
    a) Mitochondria
    b) Cytoplasm ✅
    c) Endoplasmic reticulum
    d) Nucleus
12. Glycolysis is an _______ process.
    a) Aerobic
    b) Anaerobic ✅
    c) Endergonic
    d) Oxidative
13. What is the net ATP gain from one molecule of glucose in glycolysis?
    a) 4
    b) 2 ✅
    c) 6
    d) 8
14. What is the end product of glycolysis?
    a) ATP
    b) Acetyl-CoA
    c) Pyruvate ✅
    d) NADH
15. How many molecules of NADH are produced per glucose in glycolysis?
    a) 1
    b) 2 ✅
    c) 3
    d) 4

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4. Krebs Cycle (Citric Acid Cycle)

16. Where does the Krebs cycle occur?
    a) Cytoplasm
    b) Mitochondrial matrix ✅
    c) Chloroplast
    d) Endoplasmic reticulum
17. Which molecule enters the Krebs cycle?
    a) Pyruvate
    b) Acetyl-CoA ✅
    c) Glucose
    d) Fructose
18. The Krebs cycle is an _______ process.
    a) Anaerobic
    b) Aerobic ✅
    c) Non-enzymatic
    d) Unregulated
19. How many NADH molecules are produced per Acetyl-CoA in the Krebs cycle?
    a) 1
    b) 2
    c) 3 ✅
    d) 4
20. What is the main function of the Krebs cycle?
    a) Produce ATP
    b) Generate electron carriers for ETC ✅
    c) Break down fatty acids
    d) Store energy

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5. Electron Transport Chain (ETC) & Oxidative Phosphorylation

21. Where does the ETC occur?
    a) Cytoplasm
    b) Inner mitochondrial membrane ✅
    c) Nucleus
    d) Endoplasmic reticulum
22. What is the final electron acceptor in the ETC?
    a) ATP
    b) Oxygen ✅
    c) NADH
    d) Glucose
23. The proton gradient created in the ETC powers:
    a) Glycolysis
    b) ATP synthase ✅
    c) Krebs cycle
    d) Fermentation
24. How many ATP are produced from one NADH in the ETC?
    a) 1
    b) 2
    c) 3 ✅
    d) 4
25. What is the total ATP yield from one glucose molecule through aerobic respiration?
    a) 12
    b) 24
    c) 38 ✅
    d) 50

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6. Anaerobic Respiration & Fermentation

26. What happens to pyruvate in anaerobic conditions?
    a) Enters the Krebs cycle
    b) Converts into lactate or ethanol ✅
    c) Forms Acetyl-CoA
    d) Becomes ATP
27. Lactic acid fermentation occurs in:
    a) Yeast
    b) Muscle cells ✅
    c) Plants
    d) Bacteria only
28. Alcoholic fermentation produces:
    a) Lactate
    b) Ethanol & CO₂ ✅
    c) Acetyl-CoA
    d) ATP & FADH₂
29. How many ATP does fermentation yield per glucose?
    a) 2 ✅
    b) 4
    c) 6
    d) 8
30. Why is fermentation less efficient than aerobic respiration?
    a) Produces less ATP ✅
    b) Uses more oxygen
    c) Requires mitochondria
    d) Generates too much CO₂

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7. Regulation of Energy Metabolism

31. Which enzyme regulates glycolysis?
    a) Hexokinase
    b) Phosphofructokinase ✅
    c) ATP synthase
    d) Citrate synthase
32. High ATP levels inhibit:
    a) Glycolysis ✅
    b) Fatty acid oxidation
    c) Electron transport
    d) Fermentation
33. Insulin stimulates:
    a) Glycolysis ✅
    b) Gluconeogenesis
    c) Fatty acid oxidation
    d) ATP synthase
34. Glucagon signals the liver to:
    a) Break down glycogen ✅
    b) Store glucose
    c) Inhibit glycolysis
    d) Stimulate ATP synthase
35. What is the primary function of feedback inhibition?
    a) Prevent ATP loss
    b) Maintain energy balance ✅
    c) Produce excess ATP
    d) Break down proteins

8. ATP and Energy Transfer

1. What type of reaction is ATP hydrolysis?
   a) Endergonic
   b) Exergonic ✅
   c) Anabolic
   d) Non-spontaneous
2. Which enzyme catalyzes ATP hydrolysis?
   a) ATP synthase
   b) Phosphofructokinase
   c) ATPase ✅
   d) Pyruvate kinase
3. What is released during ATP hydrolysis?
   a) Glucose
   b) Energy ✅
   c) Oxygen
   d) NADH
4. ATP is regenerated in cells through:
   a) Phosphorylation ✅
   b) Hydrolysis
   c) Reduction
   d) Fermentation
5. The phosphate bonds in ATP are often referred to as:
   a) Weak-energy bonds
   b) Peptide bonds
   c) High-energy bonds ✅
   d) Hydrogen bonds

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9. Glycolysis: Enzymes and Steps

6. Which enzyme converts glucose to glucose-6-phosphate?
   a) Hexokinase ✅
   b) Phosphofructokinase
   c) Pyruvate kinase
   d) ATP synthase
7. Which step in glycolysis consumes ATP?
   a) Pyruvate conversion
   b) Fructose-6-phosphate to fructose-1,6-bisphosphate ✅
   c) NADH formation
   d) Glucose transport
8. Glycolysis produces ATP through:
   a) Oxidative phosphorylation
   b) Substrate-level phosphorylation ✅
   c) Photophosphorylation
   d) Beta-oxidation
9. What is the intermediate step before pyruvate enters the Krebs cycle?
   a) It undergoes deamination
   b) It converts to lactate
   c) It forms Acetyl-CoA ✅
   d) It is directly used in the ETC
10. What inhibits phosphofructokinase in glycolysis?
    a) Low ATP levels
    b) High ATP levels ✅
    c) Low citrate levels
    d) High ADP levels

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10. Krebs Cycle: Key Molecules

11. How many times does the Krebs cycle turn per glucose molecule?
    a) 1
    b) 2 ✅
    c) 3
    d) 4
12. Which enzyme catalyzes the first step of the Krebs cycle?
    a) Citrate synthase ✅
    b) Hexokinase
    c) ATP synthase
    d) Pyruvate dehydrogenase
13. How many FADH₂ molecules are generated per Acetyl-CoA?
    a) 1 ✅
    b) 2
    c) 3
    d) 4
14. What is the total NADH yield from one glucose molecule in the Krebs cycle?
    a) 2
    b) 4
    c) 6 ✅
    d) 8
15. What waste product is released during the Krebs cycle?
    a) Oxygen
    b) Water
    c) Carbon dioxide ✅
    d) Ammonia

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11. Electron Transport Chain (ETC) Mechanics

16. Which molecule donates electrons to Complex I of the ETC?
    a) FADH₂
    b) NADH ✅
    c) ATP
    d) Oxygen
17. What is the role of cytochrome c in the ETC?
    a) Produces ATP
    b) Transports electrons ✅
    c) Pumps protons
    d) Accepts NADH
18. Which complex in the ETC directly synthesizes ATP?
    a) Complex I
    b) Complex III
    c) Complex IV
    d) ATP synthase ✅
19. What happens when oxygen is unavailable for the ETC?
    a) NADH accumulates ✅
    b) More ATP is produced
    c) Electron transfer speeds up
    d) ATP yield increases
20. What is the net ATP production from one molecule of glucose via oxidative phosphorylation?
    a) 10
    b) 20
    c) 34 ✅
    d) 40

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12. Anaerobic Pathways: Fermentation

21. What is the purpose of fermentation?
    a) Produce ATP directly
    b) Regenerate NAD⁺ ✅
    c) Break down fatty acids
    d) Form Acetyl-CoA
22. Which enzyme is responsible for converting pyruvate into lactate?
    a) Lactate dehydrogenase ✅
    b) Pyruvate kinase
    c) Hexokinase
    d) ATP synthase
23. Alcoholic fermentation is primarily used by:
    a) Muscle cells
    b) Yeast ✅
    c) Plants
    d) Bacteria
24. Which byproduct of fermentation causes muscle fatigue?
    a) Ethanol
    b) Carbon dioxide
    c) Lactic acid ✅
    d) Oxygen
25. What is the ATP yield per glucose in fermentation?
    a) 2 ✅
    b) 4
    c) 6
    d) 8

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13. Alternative Energy Sources

26. Beta-oxidation breaks down:
    a) Proteins
    b) Glucose
    c) Fatty acids ✅
    d) Nucleotides
27. What is the end product of beta-oxidation?
    a) Pyruvate
    b) Acetyl-CoA ✅
    c) ATP
    d) Citrate
28. Proteins are used for energy when:
    a) ATP levels are high
    b) Carbohydrate and fat stores are low ✅
    c) There is excess oxygen
    d) Glucose levels are high
29. What process removes amino groups from amino acids?
    a) Transamination
    b) Deamination ✅
    c) Fermentation
    d) Hydrolysis
30. Which macronutrient yields the most ATP per gram?
    a) Carbohydrates
    b) Proteins
    c) Lipids ✅
    d) Nucleic acids

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14. Metabolic Regulation

31. Which hormone lowers blood glucose levels?
    a) Glucagon
    b) Insulin ✅
    c) Epinephrine
    d) Cortisol
32. Which process generates glucose from non-carbohydrate sources?
    a) Glycolysis
    b) Gluconeogenesis ✅
    c) Fermentation
    d) Beta-oxidation
33. What inhibits ATP production in the Krebs cycle?
    a) Low ATP levels
    b) High ATP levels ✅
    c) High glucose levels
    d) Low citrate levels
34. High levels of ADP signal cells to:
    a) Increase ATP synthesis ✅
    b) Slow down glycolysis
    c) Reduce glucose uptake
    d) Store more fats
35. Which enzyme is a key regulator of the Krebs cycle?
    a) Citrate synthase ✅
    b) Hexokinase
    c) ATP synthase
    d) Pyruvate kinase