← The Library

Vol. VI · Biochemistry

The Metabolic Map

The pathways of the cell, drawn as one wall chart — metabolites, enzymes, and the steps between them.

Chart notes

What this metabolic map shows

Central metabolism is usually printed as one enormous wall chart, and the chart is the problem: hundreds of arrows, almost none of them explained. This one is cut down to the three pathways that carry a molecule of glucose all the way to ATP: glycolysis, the citric acid cycle, and the electron transport chain. Every step is listed below in full, enzyme by enzyme, with what goes in and what comes out.

The tables are the reference. The chart above is the same data made drillable: an arrow lights up and you name the enzyme, or you are handed a substrate and asked to click where it lands. There is no login, and your progress stays in your own browser.

Glycolysis — glucose to pyruvate

Glycolysis runs in the cytosol and needs no oxygen, which is why it is the most widely shared pathway in biology. Bacteria, yeast, and a sprinting muscle all run the same ten enzymes. The pathway spends two ATP preparing the sugar, splits the six-carbon chain into two three-carbon pieces, then earns four ATP back, a net gain of two.

The split is where most people lose the thread. Aldolase cuts fructose 1,6-bisphosphate into G3P and DHAP, but only G3P continues down the pathway, so triose phosphate isomerase converts the DHAP across rather than let half the glucose go to waste. Every step after that point happens twice per glucose.

Net per glucose: 2 pyruvate · 2 ATP · 2 NADH

StepEnzymeConversionWhat happens
1HexokinaseGlucose → Glucose 6-PSpends 1 ATP; traps glucose inside the cell
2Phosphoglucose isomeraseGlucose 6-P → Fructose 6-PAldose to ketose; nothing spent
3Phosphofructokinase-1 (PFK-1)Fructose 6-P → Fructose 1,6-BPSpends 1 ATP; the committed, rate-limiting step
4AldolaseFructose 1,6-BP → G3PSplits the six-carbon sugar; the other half is DHAP
4′AldolaseFructose 1,6-BP → DHAPThe ketone half of the same cut
5Triose phosphate isomerase (TPI)DHAP → G3PFunnels DHAP onward so both halves continue
6Glyceraldehyde-3-P dehydrogenase (GAPDH)G3P → 1,3-BPGMakes 1 NADH; adds inorganic phosphate, not ATP
7Phosphoglycerate kinase (PGK)1,3-BPG → 3-PGMakes 1 ATP by substrate-level phosphorylation
8Phosphoglycerate mutase3-PG → 2-PGRelocates the phosphate from carbon 3 to carbon 2
9Enolase2-PG → PEPRemoves water, building a high-energy enol phosphate
10Pyruvate kinase (PK)PEP → PyruvateMakes 1 ATP; irreversible finish

Ten enzymes, eleven arrows: aldolase gets a row for each product of the cleavage.

The citric acid cycle — acetyl-CoA to CO₂

Pyruvate does not enter the citric acid cycle as itself. Pyruvate dehydrogenase strips one carbon off as CO₂ and hands the remaining two-carbon acetyl group to coenzyme A, and acetyl-CoA is what the cycle actually consumes. That handoff happens in the mitochondrial matrix, and so does everything in the table below.

The cycle is a wheel rather than a line. Oxaloacetate accepts the acetyl group, eight reactions oxidize it away as two molecules of CO₂, and the final step regenerates oxaloacetate so the next acetyl group can enter. Nothing is used up except the fuel. Also known as the Krebs cycle or the TCA cycle, after the tricarboxylic acid it builds first.

Per turn: 3 NADH · 1 FADH₂ · 1 GTP · 2 CO₂. One glucose makes two acetyl-CoA, so it turns the wheel twice.

StepEnzymeConversionWhat happens
1Citrate synthaseOxaloacetate → CitrateCondenses acetyl-CoA with OAA (2C + 4C → 6C)
2AconitaseCitrate → IsocitrateIsomerization via cis-aconitate; moves the hydroxyl
3Isocitrate dehydrogenase (IDH)Isocitrate → α-KetoglutarateMakes 1 NADH, releases the first CO₂; rate-limiting
4α-Ketoglutarate dehydrogenaseα-Ketoglutarate → Succinyl-CoAMakes 1 NADH, releases the second CO₂
5Succinyl-CoA synthetaseSuccinyl-CoA → SuccinateMakes 1 GTP; the cycle's only substrate-level step
6Succinate dehydrogenase (SDH)Succinate → FumarateMakes 1 FADH₂; this enzyme is Complex II of the chain
7FumaraseFumarate → MalateAdds water across the double bond
8Malate dehydrogenase (MDH)Malate → OxaloacetateMakes 1 NADH and regenerates the acceptor

Citrate synthase appears twice on the chart: once for the oxaloacetate side, once for the acetyl-CoA arriving each turn. Succinate dehydrogenase is the only step bound to the inner membrane, which is how it doubles as Complex II.

The electron transport chain — electrons to oxygen

Glycolysis and the citric acid cycle make very little ATP directly, four molecules between them. What they really produce is reduced carriers, NADH and FADH₂, and the electron transport chain is where those get cashed.

Four complexes sit in the inner mitochondrial membrane and pass electrons down a falling energy gradient toward oxygen, the final acceptor, which becomes water. Three of the four spend the released energy pumping protons out of the matrix. Those protons then flow back in through ATP synthase and spin it like a turbine, and that rotation is what builds ATP. Peter Mitchell called this chemiosmosis and spent about fifteen years being disbelieved about it before the Nobel committee agreed with him.

Where a carrier enters decides what it is worth. NADH enters at Complex I and drives three pumps, roughly 2.5 ATP. FADH₂ enters further along at Complex II, which pumps nothing, so it is worth roughly 1.5.

ComplexAlso calledConversionWhat happens
INADH dehydrogenaseNADH → Ubiquinone (CoQ)Pumps 4 H⁺; the high-energy entry point
IISuccinate dehydrogenaseFADH₂ → Ubiquinone (CoQ)Pumps no protons; the low-energy entry point
IIICytochrome bc₁Ubiquinone → Cytochrome cPumps 4 H⁺ via the Q cycle
IVCytochrome c oxidaseCytochrome c → O₂Pumps 2 H⁺; reduces oxygen to water. Blocked by cyanide
VATP synthaseADP + Pᵢ → ATPNot an electron carrier; the proton gradient spins it

Ubiquinone and cytochrome c are mobile carriers, not complexes. They ferry electrons between the fixed pumps.

The energy ledger, one glucose end to end

Adding it up is the part exams ask for, and the honest answer is a range rather than a number.

Glycolysis (cytosol)2 ATP · 2 NADH
Pyruvate dehydrogenase, ×22 NADH
Citric acid cycle, 2 turns6 NADH · 2 FADH₂ · 2 GTP
Oxidative phosphorylation~2.5 ATP per NADH · ~1.5 per FADH₂
Total~30–32 ATP per glucose

Older textbooks say 36–38. The lower modern figure accounts for the protons spent importing phosphate and exporting ATP, and for the leak across the membrane. The range survives because the two NADH made in the cytosol have to be ferried into the mitochondrion: the malate-aspartate shuttle delivers them as NADH, while the glycerol phosphate shuttle delivers them as FADH₂ and loses about one ATP each.