Unit 4: Metabolism and Energy Transfer

Course Code: BT221C | Subject: Biology for Engineers

Coverage: Complete Syllabus + Integrated Answers for PYQs (2022, 2023, 2024)
Focus: Detailed, 15-mark ready content covering thermodynamics, metabolic pathways, and
bioenergetics.
Part 1: Thermodynamics in Biological Systems
1. Fundamental Principles of Energy Transaction
$$Answer to 2022 Q7 / 2024 Q7(a): Discuss fundamental principles of energy transfer... How is
thermodynamics applicable to biological systems? (15 / 7½ marks)$$
The "Open System" Concept:
Unlike engineered engines (often closed systems), biological organisms are Open Systems.
They constantly exchange both Matter (food, waste, gases) and Energy (heat, work) with their
surroundings. However, they strictly obey the laws of thermodynamics. In an open system,
equilibrium is rarely reached; instead, organisms maintain a Steady State, where the rate of
input equals the rate of output, maintaining constant internal conditions (Homeostasis)
despite a continuous flow of energy.
Law 1: Conservation of Energy (Enthalpy, $H$)
●​ Statement: Energy cannot be created or destroyed, only transformed from one form to
another. The total energy of the universe is constant.
●​ Biological Application:
○​ Photosynthesis: Radiant Energy (Sunlight) $\rightarrow$ Chemical Bond Energy
(Glucose). Plants act as biological solar panels, transducing photons into excited
electrons and storing that potential energy in covalent bonds.
○​ Respiration: Chemical Energy (Food) $\rightarrow$ Mechanical Energy (Muscle
Contraction) + Electrical Energy (Nerve Impulses) + Heat (Body temperature).
●​ Significance: Organisms are energy transducers, not producers. The total energy of the
system + surroundings remains constant. If an animal eats 2000 Calories of food, that
energy must either be stored (fat/glycogen), used for work, or released as heat.
Law 2: Entropy and Spontaneity (Entropy, $S$)
●​ Statement: In any spontaneous process, the total entropy (disorder/randomness) of the
universe increases ($\Delta S_{univ} > 0$). Natural processes tend towards disorder.
●​ Biological Paradox: Cells are highly ordered, organized structures (Low Entropy). How
do they exist and grow without violating the 2nd Law?
●​ Resolution (The Entropy Sink):
○​ Cells maintain their internal order (decreasing local entropy, $-\Delta S_{system}$) at
the expense of their surroundings.
○​ They continuously release Heat and simple waste molecules ($CO_2, H_2O$) into the
environment. Heat is the most disordered form of energy. By releasing heat, the cell
 increases the random motion of molecules in the surroundings, drastically increasing
environmental entropy ($+\Delta S_{surroundings}$).
○​ As long as the increase in environmental entropy is greater than the decrease in
cellular entropy, the net entropy of the universe increases, satisfying the Second Law.
Life pays for order with heat.
Gibbs Free Energy ($\Delta G$):
This function combines Enthalpy and Entropy to predict spontaneity.

$$\Delta G = \Delta H - T\Delta S$$

●​ $\Delta G < 0$: The process is Exergonic and spontaneous. The system loses free
energy and becomes more stable. (e.g., Respiration, diffusion).
●​ $\Delta G > 0$: The process is Endergonic and non-spontaneous. The system gains free
energy and becomes less stable. (e.g., Photosynthesis, Protein Synthesis).
●​ $\Delta G = 0$: The system is at Equilibrium. Biological systems avoid this state because
equilibrium = death (no capacity to do work).

2. Reaction Types: Heat vs. Free Energy

$$Answer to 2024 Q8(a): Write about Exothermic and endothermic versus endergonic and
exergonic reactions. (7½ marks)$$
This distinction is crucial for engineers. One refers to Heat ($H$), the other to Useful Work
($G$).

Feature Exothermic / Exergonic / Endergonic

Endothermic

Based On Change in Enthalpy Change in Free Energy

($\Delta H$). ($\Delta G$).

Focus Heat exchange with Spontaneity and Work

surroundings. potential.

Definition (Negative) Exothermic ($\Delta H < Exergonic ($\Delta G <

0$): Releases heat. The 0$): Releases free energy.
chemical bonds of Spontaneous. The system
products are more stable moves to a lower energy
than reactants. state.

Example: Burning wood, Example: ATP Hydrolysis,

Cellular Respiration (40% Oxidation of Glucose.
ATP, 60% Heat).

Definition (Positive) Endothermic ($\Delta H > Endergonic ($\Delta G >

 0$): Absorbs heat. The 0$): Consumes free
surroundings get colder. energy. Non-spontaneous.
Requires energy coupling.
Example: Melting ice,
Evaporation of sweat Example: DNA Replication,
(cooling effect). Muscle Contraction.

Relationship An exothermic reaction is An exergonic reaction is

often exergonic, but not the only type that can drive
always. For example, water biological work. Cells
freezing at -10°C is couple exergonic reactions
exothermic (releases heat) to drive endergonic ones.
and exergonic
(spontaneous). But protein
folding is often driven by
entropy (Hydrophobic
effect), not just enthalpy.
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3. Concept of Keq and Standard Free Energy
$$Syllabus Topic: Concept of Keq and its relation to standard free energy$$
To determine if a biological reaction will happen spontaneously under standard conditions, we
relate Gibbs Free Energy to the Equilibrium Constant ($K_{eq}$).

The Relationship:
The actual free energy change ($\Delta G$) of a reaction $A \rightleftharpoons B$ depends
on the standard free energy ($\Delta G^\circ$) and the concentrations of reactants and
products ($Q$).

$$\Delta G = \Delta G^\circ + RT \ln Q$$

At equilibrium, $\Delta G = 0$ and $Q = K_{eq}$. Therefore:

$$0 = \Delta G^\circ + RT \ln K_{eq}$$$$\Delta G^\circ = -RT \ln K_{eq}$$

●​ $R$ = Gas constant ($8.314 \text{ J/mol}\cdot\text{K}$)
●​ $T$ = Absolute Temperature (Kelvin)
Interpretation:
 ●​ If $K_{eq} > 1$ (Products are favored at equilibrium):
○​ $\ln K_{eq}$ is positive.
○​ $\Delta G^\circ$ is Negative (Spontaneous).
○​ The reaction proceeds forward towards products.
●​ If $K_{eq} < 1$ (Reactants are favored):
○​ $\ln K_{eq}$ is negative.
○​ $\Delta G^\circ$ is Positive (Non-spontaneous).
○​ The reaction proceeds backward (or requires energy input).
●​ If $K_{eq} = 1$:
○​ $\Delta G^\circ = 0$. The system is at equilibrium.

4. ATP: The Energy Currency of the Cell

$$Answer to 2022 Q8(c) / 2024 Q8(b): Discuss ATP as an energy currency... (5 - 7½
marks)$$
●​ Structure: Adenosine Triphosphate.
○​ Adenine (Nitrogenous Base).
○​ Ribose (5-Carbon Sugar).
○​ 3 Phosphate Groups ($\alpha, \beta, \gamma$) linked in a chain.
●​ Why is it "High Energy"?
○​ Electrostatic Repulsion: The phosphate groups are all negatively charged
($PO_4^{3-}$). Forcing three negative groups together in a small space creates
immense repulsion (like compressing a stiff spring).
○​ Resonance Stabilization: The products of hydrolysis ($ADP + P_i$) have greater
resonance stabilization than ATP itself.
○​ Solvation: The products ($ADP$ and $P_i$) are better solvated by water than ATP,
stabilizing the hydrolysis products.
●​ Hydrolysis Reaction:​
$$ATP + H_2O \xrightarrow{ATPase} ADP + P_i + Energy$$
○​ $\Delta G^\circ = -7.3 \text{ kcal/mol}$ (Standard conditions).
○​ In the cell, due to high $[ATP]/[ADP]$ ratios, the actual $\Delta G$ is closer to $-12
\text{ kcal/mol}$.
●​ Mechanism of Action (Energy Coupling):
○​ ATP hydrolysis is coupled to endergonic reactions. The phosphate group is often
transferred to a substrate (Phosphorylation), making the substrate unstable and
reactive.
○​ Example: Glucose + ATP $\rightarrow$ Glucose-P + ADP. The high energy of ATP is
used to create a "phosphoryl potential" in Glucose-6-Phosphate, driving the first
step of glycolysis.
Concept of Energy Charge (Atkinson):

$$Energy Charge = \frac{[ATP] + 0.5[ADP]}{[ATP] + [ADP] + [AMP]}$$

●​ It ranges from 0 (all AMP) to 1 (all ATP).
●​ Healthy cells maintain a charge of 0.8 - 0.95.
 ●​ High energy charge inhibits catabolic pathways (like glycolysis, PFK-1 inhibition) and
activates anabolic pathways (like glycogen synthesis).

5. High Energy Compounds (Alternatives to ATP)

While ATP is the main currency, other molecules also store high energy:

Compound ΔG∘ of Hydrolysis Significance

(kJ/mol)

Phosphoenolpyruvate -61.9 Highest energy phosphate.

(PEP) Drives ATP synthesis in
Glycolysis (Step 10).

1,3-Bisphosphoglycerate -49.3 High energy intermediate in

Glycolysis (Step 7).

Creatine Phosphate -43.0 Energy reservoir in muscles

for bursts of activity. Can
regenerate ATP rapidly.

ATP -30.5 The Goldilocks Molecule:

Intermediate energy level
allows it to be both made
(by PEP) and used
efficiently.

Glucose-6-Phosphate -13.8 Low energy phosphate

ester. Requires ATP to be
formed.

Part 2: Metabolic Pathways (Glycolysis & Krebs

Cycle)
1. Glycolysis (The Breakdown of Glucose)
$$Answer to 2022 Q8(b) / 2023 Q7: What are the silent features of glycolysis? Mention the
steps... (15 marks)$$
●​ Definition: The metabolic pathway that converts Glucose ($C_6$) into 2 molecules of
Pyruvate ($C_3$). "Glyco" = Sugar, "Lysis" = Splitting.
●​ Location: Cytoplasm (Cytosol).
●​ Nature: Anaerobic (Does not require Oxygen). It is the universal pathway found in all
organisms (bacteria to humans).
 ●​ Net Yield: 2 ATP + 2 NADH per Glucose.
Detailed Steps (10 Steps in 2 Phases):

Phase I: Investment Phase (Consumes 2 ATP)

Goal: To trap glucose and destabilize its structure.
1.​ Phosphorylation: Glucose is phosphorylated by Hexokinase to form
Glucose-6-Phosphate. (Uses 1 ATP).
○​ Purpose: Traps glucose inside the cell (charged molecules cannot cross the lipid
bilayer).
○​ Regulation: Hexokinase is inhibited by its product, Glucose-6-Phosphate (Feedback
Inhibition).
2.​ Isomerization: Glucose-6-P (Aldose) is converted to Fructose-6-Phosphate (Ketose)
by Phosphoglucoisomerase.
○​ Purpose: Sets up the molecule for symmetrical cleavage later.
3.​ Phosphorylation (The Major Control Point): Fructose-6-P is phosphorylated by
Phosphofructokinase-1 (PFK-1) to form Fructose-1,6-bisphosphate. (Uses 1 ATP).
○​ Significance: This is the Rate Limiting Step and the "Point of No Return".
○​ Regulation: PFK-1 is inhibited by high levels of ATP and Citrate (signals "we have
enough energy"), and activated by AMP and ADP (signals "we need energy").
4.​ Cleavage: The 6-carbon sugar splits into two 3-carbon sugars:
Glyceraldehyde-3-Phosphate (G3P) and Dihydroxyacetone Phosphate (DHAP) via the
enzyme Aldolase.
5.​ Isomerization: DHAP is converted into G3P by Triose Phosphate Isomerase.
○​ Result: We now have 2 molecules of G3P to proceed to the payoff phase.
Phase II: Payoff Phase (Produces 4 ATP & 2 NADH)
(Note: All reactions occur twice per glucose molecule)
6.​ Oxidation & Phosphorylation: G3P is oxidized by G3P Dehydrogenase.
○​ $NAD^+$ is reduced to NADH (carrying high-energy electrons).
○​ Inorganic phosphate ($P_i$) is added to form 1,3-Bisphosphoglycerate (1,3-BPG).
This bond is very high energy.
7.​ Substrate-Level Phosphorylation: A phosphate is transferred from 1,3-BPG to ADP to
make ATP.
○​ Enzyme: Phosphoglycerate Kinase.
○​ Product: 3-Phosphoglycerate. This reaction pays back the 2 ATP debt from Phase I.
8.​ Isomerization: 3-Phosphoglycerate $\rightarrow$ 2-Phosphoglycerate (phosphate
moves position) via Phosphoglycerate Mutase.
9.​ Dehydration: Removal of water by Enolase forms Phosphoenolpyruvate (PEP).
○​ Significance: PEP has an extremely high energy phosphate bond ($\Delta G = -61.9$
kJ/mol), higher than ATP.
10.​Substrate-Level Phosphorylation: PEP transfers phosphate to ADP to make ATP via
Pyruvate Kinase.
○​ Product: Pyruvate.
 ○​ Regulation: Pyruvate Kinase is activated by Fructose-1,6-bisphosphate
(Feed-forward activation) and inhibited by ATP.
Fate of Pyruvate:
●​ Aerobic (Humans/Plants): Enters Mitochondria $\rightarrow$ Acetyl-CoA $\rightarrow$
Krebs Cycle $\rightarrow$ $CO_2 + H_2O$ (Total oxidation).
●​ Anaerobic (Humans/Bacteria): Converted to Lactate via Lactate Dehydrogenase. This
reaction is crucial because it regenerates $NAD^+$ required for Step 6, allowing
glycolysis to continue in the absence of oxygen. (Causes muscle burn).
●​ Anaerobic (Yeast): Converted to Ethanol + CO2 via Pyruvate Decarboxylase and
Alcohol Dehydrogenase. (Basis of brewing/baking).
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2. Krebs Cycle (TCA Cycle / Citric Acid Cycle)
$$Answer to 2024 Q7(b): Glycolysis and Krebs cycle... (Part of question).$$
●​ Location: Mitochondrial Matrix (Eukaryotes).
●​ Prerequisite (Link Reaction): Pyruvate enters the mitochondria and is converted to
Acetyl-CoA by the massive Pyruvate Dehydrogenase Complex (PDC). (Releases $1
CO_2$ and $1 NADH$). This connects Glycolysis to the Krebs Cycle.
Steps of the Cycle (8 Enzymatic Steps):
1.​ Condensation: Acetyl-CoA (2C) combines with Oxaloacetate (4C) to form Citrate (6C).
○​ Enzyme: Citrate Synthase.
○​ Regulation: Inhibited by ATP, NADH, Succinyl-CoA (Product inhibition).
2.​ Isomerization: Citrate is rearranged into Isocitrate (via cis-Aconitate). Enzyme:
Aconitase. Moves the -OH group to set up decarboxylation.
3.​ Oxidative Decarboxylation 1: Isocitrate is oxidized to $\alpha$-Ketoglutarate (5C).
○​ Enzyme: Isocitrate Dehydrogenase.
○​ Releases $CO_2$.
○​ Produces NADH.
○​ Regulation: Activated by ADP; Inhibited by ATP/NADH.
4.​ Oxidative Decarboxylation 2: $\alpha$-Ketoglutarate is oxidized to Succinyl-CoA
(4C).
○​ Enzyme: $\alpha$-Ketoglutarate Dehydrogenase.
○​ Releases $CO_2$.
○​ Produces NADH.
○​ This step is structurally similar to the Link Reaction.
5.​ Substrate-Level Phosphorylation: Succinyl-CoA is converted to Succinate.
○​ The high energy thioester bond breakage drives the formation of GTP (which
converts to ATP).
○​ Enzyme: Succinyl-CoA Synthetase.
6.​ Oxidation: Succinate oxidized to Fumarate.
○​ Enzyme: Succinate Dehydrogenase (This enzyme is embedded in the inner
mitochondrial membrane and is part of the Electron Transport Chain).
○​ Produces $FADH_2$.
7.​ Hydration: Water is added to Fumarate to form Malate. Enzyme: Fumarase.
8.​ Dehydrogenation: Malate is oxidized to regenerate Oxaloacetate.
○​ Enzyme: Malate Dehydrogenase.
○​ Produces NADH.
○​ Oxaloacetate is now ready to bond with a new Acetyl-CoA to restart the cycle.
Total Yield (Per Glucose): Since 1 Glucose = 2 Pyruvates = 2 Turns of Cycle.
●​ $6 NADH$ (3 per turn)
●​ $2 FADH_2$ (1 per turn)
 ●​ $2 ATP/GTP$ (1 per turn)
●​ $4 CO_2$ (2 per turn)
Amphibolic Nature: The TCA cycle is not just for breakdown (Catabolism). It is a metabolic
hub where intermediates are used for synthesis (Anabolism):
●​ Oxaloacetate $\rightarrow$ Precursor for Glucose (Gluconeogenesis) and Amino Acids
(Aspartate).
●​ Succinyl-CoA $\rightarrow$ Precursor for Heme (Hemoglobin) and Chlorophyll.
●​ Citrate $\rightarrow$ Precursor for Fatty Acids and Sterols (exported to cytoplasm).
●​ $\alpha$-Ketoglutarate $\rightarrow$ Precursor for Glutamate and other amino acids.
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Part 3: Photosynthesis (Synthesis of Glucose)

1. Photosynthesis: Overview & Light Reaction
$$Answer to 2022 Q8(a) / 2023 Q8: Describe the process of synthesis of glucose from
oxygen and carbon dioxide. (15 marks)$$
●​ Definition: The physiochemical process by which green plants use light energy to drive
the synthesis of organic compounds (Glucose).
●​ Equation: $6CO_2 + 12H_2O \xrightarrow{Light, Chlorophyll} C_6H_{12}O_6 + 6H_2O +
6O_2$.
●​ Location: Chloroplasts.
Stage 1: Light-Dependent Reaction (The "Photo" Part)
●​ Location: Thylakoid Membranes.
●​ Goal: Convert Light Energy $\rightarrow$ Chemical Energy (ATP + NADPH).
●​ Mechanism (Z-Scheme/Non-Cyclic Photophosphorylation):
1.​ Excitation: Light hits Photosystem II (P680). Electrons get excited and jump to a
primary electron acceptor.
2.​ Photolysis of Water: To replace the lost electrons, water is split by the Oxygen
Evolving Complex:​
$$2H_2O \rightarrow 4H^+ + 4e^- + O_2$$​
​
This is the source of the Oxygen we breathe.
3.​ Electron Transport Chain (ETC): Electrons travel from PSII to PSI through carriers
(Plastoquinone, Cytochrome b6f, Plastocyanin). As electrons move, protons ($H^+$)
are pumped into the thylakoid lumen, creating a gradient.
4.​ Photophosphorylation: The proton gradient (Proton Motive Force) drives ATP
Synthase to produce ATP.
5.​ Reduction: Electrons reach Photosystem I (P700), get re-excited by light, and are
finally used to reduce $NADP^+$ to NADPH.

2. Calvin Cycle (Light-Independent Reaction)

●​ Location: Stroma of Chloroplast.
●​ Goal: Use ATP & NADPH to fix $CO_2$ into Glucose.
Steps (C3 Cycle):
1.​ Carbon Fixation (Carboxylation): Atmospheric $CO_2$ combines with a 5-carbon
sugar acceptor Ribulose-1,5-bisphosphate (RuBP).
○​ Enzyme: Rubisco (Ribulose Bisphosphate Carboxylase Oxygenase).
○​ Product: An unstable 6C compound that immediately splits into two molecules of
3-Phosphoglycerate (3-PGA).
2.​ Reduction:
 ○​ 3-PGA is phosphorylated by ATP.
○​ It is then reduced by NADPH.
○​ Product: Glyceraldehyde-3-Phosphate (G3P) (a triose sugar).
3.​ Regeneration:
○​ For every 3 turns of the cycle, 1 G3P exits to make glucose.
○​ The remaining 5 G3P molecules are rearranged (using ATP) to regenerate 3
molecules of RuBP. This ensures the cycle can continue to accept new $CO_2$.
4.​ Synthesis:
○​ Two G3P molecules exiting the cycle combine to form Fructose, which isomerizes to
Glucose, which polymerizes to Starch (storage) or Sucrose (transport).
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Photorespiration (The Glitch):
Rubisco is an imperfect enzyme. It can bind $O_2$ instead of $CO_2$ (Oxygenase activity).
●​ This occurs when $O_2$ levels are high and temperatures are high.
●​ Result: It breaks down RuBP into phosphoglycolate, wasting ATP and releasing previously
fixed $CO_2$ without producing sugar. This can reduce photosynthetic efficiency by
25-50%.
●​ Adaptation: C4 Plants (like maize, sugarcane) evolved a spatial separation (Mesophyll
vs Bundle Sheath cells) to concentrate $CO_2$ around Rubisco, eliminating
 photorespiration.

3. Energetics Summary (ATP Yield)

$$Answer to 2024 Q8(b): Explain concept of energy change... (Part of question).$$
Total ATP Calculation (Aerobic Respiration):
1.​ Glycolysis:
○​ 2 ATP (net).
○​ 2 NADH ($\approx$ 3-5 ATP, depending on the shuttle used to enter mitochondria).
2.​ Link Reaction:
○​ 2 NADH ($\approx$ 5 ATP).
3.​ Krebs Cycle:
○​ 2 GTP (= 2 ATP).
○​ 6 NADH ($\approx$ 15 ATP).
○​ 2 FADH2 ($\approx$ 3 ATP).
4.​ Total: 30-32 ATP per Glucose molecule (Modern estimate). Old text books may say
36-38 ATP.
Efficiency:
●​ Combustion of glucose releases 686 kcal/mol.
●​ Cellular respiration captures approx 270 kcal/mol as ATP.
●​ Efficiency: $\approx 40\%$.
●​ The remaining 60% is lost as Heat. This heat is not "waste" for warm-blooded animals; it
is essential for maintaining body temperature (homeostasis) and enzyme kinetics.