Respiration

After pyruvate (a 3-carbon molecule) is synthesized by glycolysis, it moves into the mitochondria and is oxidized to form carbon dioxide (a 1-carbon molecule) and acetyl CoA (a two carbon molecule). Cells can also make acetyl CoA from fats and amino acids and this is how cells often derive energy, in the form of ATP, from molecules other than glucose or complex carbohydrates.

After acetyl CoA forms, it enters into a series of nine sequential enzymatic reactions, known as the citric acid cycle. These reactions are so named because the first reaction makes one molecule of citric acid (a 6-carbon molecule) from one molecule of acetyl CoA (a 2-carbon molecule) and one molecule of oxaloacetic acid (a 4-carbon molecule). A complete round of the citric acid cycle expels two molecules of carbon dioxide and regenerates one molecule of oxaloacetic acid, hence the cyclic nature of these reactions. The citric acid cycle is sometimes called the Krebs cycle, in honor of Hans Krebs, the English biochemist who first proposed that pyruvate is broken down by a cycle of biochemical reactions.

The citric acid cycle has several important features:

1. It makes NADH (reduced nicotinamide adenine dinucleotide) and FADH₂ (reduced flavin adenine dinucleotide), high energy molecules which are used to make ATP in the electron transfer chain (see below). For each glucose molecule which initially enters glycolysis, the citric acid cycle makes 6 molecules of NADH and 2 molecules of FADH₂.
2. It makes GTP (guanosine triphosphate) by a process known as substrate-level phosphorylation. GTP is a high energy molecule which cells can easily use to make ATP by a separate mitochondrial reaction. For each molecule of glucose which initially enters glycolysis, the citric acid cycle makes two molecules of ATP.
3. Some of the intermediates of the citric acid cycle reactions are used to make other important compounds. In particular, certain intermediates are used to synthesize amino acids, the building blocks of proteins, nucleotides, the building blocks of DNA, and other important molecules.