makeup friday lecture

Review of Carbon Oxidation & the TCA Cycle

During the previous unit we asked: How many turns of the TCA cycle are required to fully oxidize the two carbons that enter as an acetyl group? The answer is that it takes several successive cycles; the textbook highlights those incoming carbons in blue to help you trace them as they are first converted into a carboxylic-acid group and then released as \text{CO}_2 over subsequent rounds.

An illustrative experiment (Dr. Hathelin, grasshoppers fed ^{14}\text C-labelled food) confirmed that complete oxidation of an entering carbon skeleton requires multiple passes through the cycle before all labelled carbon is lost as \text{CO}_2.

Key recap points

• Bridge (pyruvate-to-acetyl-CoA) reaction – first oxidative decarboxylation, first carbon lost.

• Each TCA turn yields three reduced electron carriers – \text{NADH} and \text{FADH}_2 – more than any earlier stage.

• Stage 3 (Unit 3) = oxidative phosphorylation: electrons from those carriers pass through a series of respiratory complexes, oxygen becomes the final acceptor, water is formed, a proton gradient is established, and Complex V (ATP synthase) converts the gradient’s potential energy into ATP.

Why We Must Understand Membranes Before Ox-Phos

Oxidative phosphorylation is impossible without a selectively permeable biological membrane that can separate two aqueous environments, maintain an electro-chemical gradient, and let Complex V harness that gradient. Thus we revisit the three requirements for life (original slide from Unit 1):

1. Selective isolation – membranes distinguish inside vs. outside.

2. Chemical activity – enzymes carry out metabolism.

3. Genetic information – not our focus in this course.

Selective Isolation, Compartmentation & Metabolic Regulation

• Plasma membrane separates the extracellular milieu from the cytosol.

• Eukaryotes super-impose organelle membranes to create micro-environments; each compartment can fine-tune substrate concentrations, pH, ion levels, etc.

• Membrane‐controlled concentrations let cells push certain reactions far from equilibrium. Opening a “flood-gate” (an enzyme or transporter) can then unleash a large metabolic flux instantaneously.

• Example metaphor: without compartmentation anabolic assembly (building complex molecules) and catabolic disassembly (burning food) would happen in the same space at the same time → futile ATP cycling and uncontrollable heat loss.

Chemical Composition of Biological Membranes

Membranes are self-assembled phospholipid bilayers – no covalent bonds between individual lipids, only weak forces:

• Hydrophobic effect (primary driver)

• Van der Waals forces between tightly packed hydrocarbon tails

• Hydrogen bonds / ionic interactions among polar head-groups & surrounding water

Typical thickness of the hydrophobic core ≈ 30\,\text{Å}. All biological membranes (plasma membrane, ER, Golgi, lysosomes, vesicles, etc.) share this architecture. Some organelles – nucleus and mitochondrion – feature a double membrane. Their dual envelopes fit the endosymbiotic theory: one membrane comes from the engulfed ancestor, the second from the host cell’s plasma membrane.

Density & Phase Behavior Demonstrations

• Lipid density ≈ 0.8-0.9\,\text{g mL}^{-1} vs. water 1.0\,\text{g mL}^{-1} vs. sucrose 1.3\,\text{g mL}^{-1}. Density alone, however, is not why fat beads float; the real driver is hydrophobic exclusion by water.

• Classroom beaker experiment: pure water + mixed fatty acids & phospholipids → lipids migrate to the air–water interface (heads down, tails up). Forcing them into bulk water yields self-assembled structures:

  • Micelle – single-tail lipids (e.g.
    fatty acids) pack into a sphere.

  • Bilayer vesicle – double-tail phospholipids cannot pack as a micelle because the kinked second tail creates voids; instead two leaflets align tail-to-tail.

• Culinary analogy – chicken broth surface fat droplets, or why olive oil separates from vinegar.

Lipid Chemistry Basics

Fatty Acids – the Building Unit

General formula: polar carboxyl head + non-polar hydrocarbon tail. Biological chain lengths n=12\text{–}24 carbons, almost always even because biosynthesis adds 2-carbon acetate units (acetyl-CoA).

Saturation & Double Bonds

• Saturated – only C–C single bonds; chains are straight; pack tightly; maximize Van der Waals contacts.

• Unsaturated – one or more C=C double bonds. The geometry matters:

  • cis – introduces a kink → loosens packing → fewer Van der Waals interactions → increases fluidity.

  • trans – chain remains nearly straight → packs almost like saturated fat.

Example nomenclature (you must interpret it): 18:1\,c\Delta^9

• 18 carbons total

• 1 double bond

• c = cis

• first C of the double bond is carbon 9 (counting from the carboxyl end).

Alternative ω (n-) naming counts from the terminal (ω) methyl carbon. ω-3 means the first double bond starts 3 carbons from the end – important for neural myelin synthesis (fish oil).

Even More Numbers to Remember

• Hydrophobic core of a membrane ≈ 30 Å.

• Glycogen stores sustain humans < 24 h without food; long-term energy is fat.

• Biologically common tails: \text{C}{16} (palmitic), \text{C}{18} (stearic, oleic), \text{C}{20}, \text{C}{22}, \text{C}_{24}.

Storage Lipids – Triacylglycerols (TAGs)

Structure = glycerol + 3 fatty acyl esters (no polar head). Extremely hydrophobic → excellent compact energy store. Accumulate in adipocytes, forming bulk adipose tissue surrounding organs and under skin. TAGs deliver more ATP per carbon than carbohydrates because their carbons are more reduced (fewer C–O bonds to start with).

Clinical note – adipocytes serve additional roles: heat insulation, cushioning, endocrine signaling (leptin, adiponectin).

Membrane Fluidity & Everyday Examples

• Olive oil (rich in cis-monounsaturated oleic 18:1) is liquid at room temperature because poor packing ↓ Van der Waals cohesion.

• Coconut oil (mostly saturated 12:0, 14:0) solidifies easily – tight packing ↑ melting point.

• Chemical hydrogenation (margarine production, deep-fryer reuse) converts cis to trans bonds → semi-solids → introduces dietary trans fats.

Health & Ethics of Trans Fatty Acids

• Natural occurrence in milk fat ≈ 0.1\%.

• Industrial processing yields high levels – snack chips, fast-food frying oils.

• Humans possess few enzymes able to metabolize trans fats → they circulate & deposit in vasculature → associations with cardiovascular disease, atherosclerosis, type-2 diabetes. Mechanistic hypotheses:

  • Accumulation due to metabolic inertness.

  • Aberrant metabolites interfere with normal lipid signaling pathways.

Physical Basis of Membrane Function

• Lipids move laterally in the bilayer – semi-fluid mosaic. No specific directional Van der Waals preference → a “2-D sea” in which proteins can drift, rotate, or cluster.

• Weak interactions make the membrane strong enough yet flexible; a covalently cross-linked ‘exoskeleton’ would cripple motility, vesicle budding, cytokinesis, etc.

Double-Membrane Organelles & Endosymbiosis

• Nucleus – host membrane + engulfed ancestor membrane (possibly viral).

• Mitochondrion – striking resemblance to modern α-proteobacteria; inner membrane retains bacterial-style lipid composition.

• Recent lab observation: amoeba swallowed algae but did not digest them → a living snapshot of potential endosymbiotic events.

Classroom Metaphors, Examples & Demonstrations

1. Flood-gate analogy – an enzyme opening instantly drives a pathway set far from equilibrium.

2. Chicken-soup fat layer – why hydrophobic molecules segregate at the surface.

3. Oil vs. water beaker – micelles versus bilayers under forced mixing.

4. Olive vs. coconut oil taste-and-melt demo – linking saturation level to melting point.

5. Radiolabelled grasshopper carbon tracing – multi-cycle carbon loss.

Connection to Earlier & Future Units

• Unit 1 enzyme kinetics → now explains membrane semi-fluidity (lipid diffusion resembles substrate diffusion).

• Unit 2 glycolysis & TCA → supplied reduced carriers; Unit 3 will convert them to ATP via the membrane-bound respiratory chain.

• Regulatory themes (enzyme quantity, allostery, substrate availability) now acquire a spatial dimension – membranes let the cell partition reactants.

Ethical / Practical / Societal Angles

• Nutritional guidelines removing artificial trans fats (FDA rulings, WHO global initiative) aim to reduce preventable cardiovascular events.

• Fish-oil supplementation debates: balancing sustainability of fisheries with neuro-developmental benefits of ω-3 lipids.

• Industrial hydrogenation vs. consumer perception – “It’s not butter!” marketing vs. biochemical reality.

Essential Take-Home Messages

• Biological membranes are phospholipid bilayers formed by the hydrophobic effect and stabilized by weak forces.

• Fluidity is modulated by fatty-acid chain length, saturation, cis/trans geometry, temperature, and cholesterol.

• Compartmentation underlies metabolic control and enables oxidative phosphorylation.

• Triacylglycerols are the major long-term energy reserve; saturated vs. unsaturated composition dictates physical state.

• Trans fats are rare in nature, created industrially, poorly metabolized, and epidemiologically linked to disease.

These principles set the stage for our deep dive into electron-transport complexes, proton-motive force, and ATP synthesis in the remainder of Unit 3.