Energy & Metabolism

Every ATP your cells make comes from breaking glucose apart, piece by piece, and capturing the released energy. Three stages. Two can run without oxygen. One cannot. The one that can't is where 90% of your energy comes from.

Cellular respiration is the process of converting glucose (C₆H₁₂O₆) into ATP using oxygen. Net equation: C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + ~36–38 ATP

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Why ATP — what it actually does

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ATP (adenosine triphosphate) is the universal energy currency of the cell. When a cell needs energy — to contract a muscle, pump ions, synthesize a protein — it breaks the bond between the second and third phosphate group of ATP. That bond releases about 7.3 kcal/mol of free energy. The leftover molecule is ADP (adenosine diphosphate). Cellular respiration uses the energy from glucose to reattach that phosphate group, regenerating ATP from ADP. The cell is constantly cycling ATP ↔ ADP, never making ATP from scratch but recycling the same molecules over and over.

💡 A human at rest recycles their body weight in ATP roughly every day. You don't store it — you cycle it continuously.

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NADH and FADH₂ — the electron carriers

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Glycolysis and the Krebs cycle don't make most of their ATP directly. Instead they strip electrons from glucose intermediates and load them onto carrier molecules: NAD⁺ becomes NADH, FAD becomes FADH₂. These are like charged batteries. They carry electrons to the electron transport chain, where the energy from those electrons is used to make most of the ATP. Without the ETC, NADH and FADH₂ would just pile up and glycolysis would grind to a halt — which is exactly what happens in anaerobic conditions, requiring fermentation to recycle them.

Glycolysis — "glucose splitting" — happens in the cytoplasm, requires no oxygen, and breaks one 6-carbon glucose into two 3-carbon pyruvate molecules. NET gain: 2 ATP and 2 NADH.

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Glycolysis and your yogurt — the connection

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S. thermophilus runs glycolysis to break down lactose (after splitting it into glucose and galactose). The pyruvate it produces doesn't go into the Krebs cycle — it gets converted to lactic acid instead (fermentation). That's anaerobic glycolysis: the same first 10 steps, but pyruvate goes sideways into lactate production instead of forward into the mitochondria. The lactic acid accumulation drops the pH in your vat. Glycolysis is the same in your cells and in your cultures — just different fates for the pyruvate.

The Krebs cycle (citric acid cycle) happens in the mitochondrial matrix. Each pyruvate first gets converted to acetyl-CoA (releasing CO₂). Then acetyl-CoA enters the cycle — 8 steps, spinning twice per glucose. Direct yield: 2 ATP, 6 NADH, 2 FADH₂ — but its real job is loading electron carriers for the ETC.

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Why it's called a cycle — and why it matters

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The cycle ends by regenerating oxaloacetate — the same 4-carbon molecule it started with. That's why it can keep spinning. Acetyl-CoA enters each turn, gets fully oxidized to CO₂, and the energy is captured as NADH and FADH₂. If oxaloacetate runs low (starvation, very low carb diet), the cycle slows dramatically. The Krebs cycle is essentially a carbon-processing machine that strips electrons from carbon compounds and loads them onto electron carriers for the ETC. The CO₂ you breathe out is the carbon from your food, exhausted from the Krebs cycle.

The Electron Transport Chain is where most ATP is made — ~28–32 per glucose. Located in the inner mitochondrial membrane. NADH and FADH₂ deliver electrons; oxygen accepts them at the end. The energy drives ATP synthase.

The ETC: electrons flow downhill through protein complexes, pumping H⁺ ions. ATP synthase uses the H⁺ gradient to spin and make ATP

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Chemiosmosis — how ATP synthase works

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As electrons move through Complexes I, III, and IV of the ETC, they release energy that's used to pump H⁺ ions (protons) from the matrix into the intermembrane space. This creates a proton gradient — high concentration outside, low inside. H⁺ ions flow back through ATP synthase (like water through a turbine), and that flow physically rotates the ATP synthase enzyme, which drives the phosphorylation of ADP to ATP. This is called chemiosmosis — using a chemical gradient to drive synthesis. ~2.5 ATP per NADH, ~1.5 ATP per FADH₂.

💡 NADH enters at Complex I — higher yield. FADH₂ enters at Complex II — bypasses Complex I, so lower yield. That's why NADH = ~2.5 ATP and FADH₂ = ~1.5 ATP.

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Why you need oxygen — the final electron acceptor

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Electrons need somewhere to go at the end of the chain. Oxygen is the final electron acceptor — it accepts electrons at Complex IV and combines with H⁺ to form water (H₂O). Without oxygen, electrons back up in the chain, NADH can't unload its electrons, and the whole ETC stops. When the ETC stops, the Krebs cycle stops (NADH piles up). Only glycolysis continues — but only if fermentation recycles the NADH. This is exactly why aerobic respiration requires oxygen and why anaerobic conditions dramatically reduce ATP yield.

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The ATP count — where each one comes from

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Glycolysis
2 ATP direct
2 NADH → ~5 ATP

Pyruvate ox.
0 ATP direct
2 NADH → ~5 ATP

Krebs ×2
2 ATP direct
6 NADH → ~15 ATP
2 FADH₂ → ~3 ATP

Total: ~30–32 ATP (modern estimate) or ~36–38 (older textbook estimate)

When there's no oxygen — or not enough — the ETC shuts down. Cells switch to fermentation to regenerate NAD⁺ so glycolysis can keep running. Only 2 ATP per glucose. Two main types: lactic acid fermentation and alcoholic fermentation.

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Yogurt fermentation — lactic acid in action

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S. thermophilus and L. bulgaricus are homofermentative — they almost exclusively produce lactic acid from fermentation. No alcohol, no CO₂ (unlike baker's yeast). The lactic acid they produce is what drops the pH in your vat during fermentation. The pH drop causes casein proteins to unfold and aggregate around pH 4.6 (the isoelectric point of casein) — that's what forms the yogurt gel. The biochemistry is: glucose → 2 pyruvate → 2 lactate. The NAD⁺ recycling is what makes the whole thing keep running. When the pH gets too low, the organisms slow down and stop — self-limiting by their own metabolic byproduct.

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Muscle fatigue — same chemistry as your vat

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When muscles work harder than oxygen delivery allows, they switch to lactic acid fermentation. Lactate accumulates. It's not actually the lactate causing the burn — it's the H⁺ ions (the acid part of lactic acid) interfering with muscle fiber contraction and dropping local pH. Same chemistry as your yogurt: lactic acid → H⁺ accumulation → inhibition. A fighter's burning muscles and your souring vat are running the same reaction. Lactate threshold training increases the muscle's ability to clear lactate and buffer H⁺ before fatigue sets in.

ATP tally

Per glucose

Glycolysis: 2 ATP
Pyruvate ox: 0 ATP
Krebs ×2: 2 ATP
ETC: ~28–32 ATP

Total: ~32–36 ATP

Anaerobic only:
2 ATP per glucose
No ETC, no Krebs

Key vocabulary

ATP

Adenosine triphosphate — universal energy currency. ADP + phosphate + energy → ATP. Breaking the bond releases ~7.3 kcal/mol.

NADH / FADH₂

Electron carriers. Load electrons in glycolysis/Krebs, deliver them to ETC. NADH yields ~2.5 ATP; FADH₂ yields ~1.5 ATP.

Pyruvate

3-carbon end product of glycolysis. Goes to Krebs (aerobic) or becomes lactate/ethanol (anaerobic).

Acetyl-CoA

2-carbon molecule that enters the Krebs cycle. Made from pyruvate (losing 1 CO₂) or from fatty acid breakdown.

Chemiosmosis

H⁺ gradient across inner mitochondrial membrane drives ATP synthase. ~90% of ATP made this way.

Substrate-level phosphorylation

Direct ATP production in glycolysis and Krebs — enzyme transfers phosphate directly to ADP. Doesn't need ETC.

Fermentation

Anaerobic process to regenerate NAD⁺. NOT for ATP — for keeping glycolysis running. Produces lactate or ethanol.

Exam reminders

Glycolysis: cytoplasm, no O₂ needed. Krebs + ETC: mitochondria, need O₂.

NET 2 ATP from glycolysis (4 made − 2 used). NOT 4.

Krebs runs twice per glucose — once per pyruvate.

ETC makes most ATP via chemiosmosis, not directly.

Oxygen is the final electron acceptor in ETC. Without O₂, ETC stops.

Fermentation regenerates NAD⁺ — it does NOT make extra ATP.

Lactate ≠ lactic acid exactly — at physiological pH, most dissociates to lactate + H⁺. The H⁺ causes the burn.