Fates of Pyruvate

Each pyruvate produced by glycolysis has three possible fates, depending on the presence of oxygen and the cell type. This is the branch point where glucose metabolism splits into “aerobic with full oxidation” or “anaerobic with fermentation.”

Fate 1: Acetyl-CoA (Aerobic) - The Main Pipeline

If oxygen is available, pyruvate enters the mitochondrial matrix and is oxidatively decarboxylated by the pyruvate dehydrogenase (PDH) complex:

$\text{Pyruvate + CoA + NAD}^+ \rightarrow \text{Acetyl-CoA + CO}_2 + \text{NADH}$

Each glucose produces 2 pyruvate → 2 acetyl-CoA + 2 CO2 + 2 NADH (in the mitochondrial matrix). Acetyl-CoA then enters the TCA cycle (also called the citric acid cycle or Krebs cycle) for full oxidation. The TCA cycle strips more electrons as NADH and FADH2, which feed the electron transport chain (ETC). The ETC pumps protons, and ATP synthase uses the proton gradient to make ATP. This is the main energy pipeline of aerobic respiration, covered in Chapter 10.

PDH requires 5 coenzymes: TPP (B1), FAD (B2), NAD+ (B3), CoA (B5), and lipoic acid. Mnemonic: “Tender Loving Care For Nancy” = TPP, Lipoic acid, CoA, FAD, NAD.

Fate 2: Lactate (Anaerobic in Animals)

When O2 is scarce or mitochondria are absent (red blood cells have no mitochondria), pyruvate is reduced to lactate:

$\text{Pyruvate + NADH} \xrightarrow{\text{lactate dehydrogenase}} \text{Lactate + NAD}^+$

Why bother? Glycolysis requires NAD+ to keep going (step 6, GAPDH). Without the ETC to recycle NADH back to NAD+, the NAD+ pool would run out. Making lactate regenerates NAD+ so glycolysis can continue (~2 ATP per glucose, slow but oxygen-independent).

Fate 3: Ethanol (Yeast Fermentation)

In yeast, pyruvate is decarboxylated to acetaldehyde, then reduced to ethanol:

$\text{Pyruvate} \rightarrow \text{Acetaldehyde + CO}_2 \rightarrow \text{Ethanol}$

The second step uses NADH, regenerating NAD+ just like lactic acid fermentation. This is how beer, wine, and bread dough are made - yeast ferment sugar, producing CO2 (bubbles) and ethanol (alcohol).