Step 1: Citrate synthase. The first step is to put energy into the system. ...

Step 2: Aconitase. ...

Step 3: Isocitrate dehydrogenase. ...

Step 4: α-Ketoglutarate dehydrogenase. ...

Step 5: Succinyl-CoA synthetase. ...

Step 6: Succinate dehydrogenase. ...

Step 7: Fumarase. ...

Step 8: Malate dehydrogenase

The Krebs Cycle (also known as the Citric Acid or Tricarboxylic Acid (TCA) cycle) is the process through which aerobic cellular metabolism occurs. Hans Krebs received the 1953 Nobel Prize in Medicine for his “discovery” of the citric acid cycle. This cycle involves a series of reactions involving a (1) a substrate, Oxaloacetate, that is modified in every reaction, (2) Acetyl–CoA, from which energy is extracted, (3) energy transport reactants, which collect the extracted energy, and (4) the controlling enzymes, which regulate the steps of the cycle. This cycle is ubiquitous in living organisms, single and multi-celled, both plants and animals — including humans. Organizationally, the process is often divided into 8 steps, one for each controlling enzyme, usually beginning with the combination of the Oxaloacetate substrate to the Acetyl–CoA, which is produced from either glycolysis or pyruvate oxidation.

But because of the cyclical nature of the process, different methods of categorizing the reactions and their reactants, as well as ongoing scientific investigation, there is some variation in terminology, organization, and detail. Also, while the Krebs cycle is a topic in elementary science and biology, it is also studied in detail in advanced collegiate biology and biochemistry courses which can lead to respectively over or under simplification. Because of these issues, tutors and students should exercise care when utilizing this summary and diagram to ensure that the language their answers use correspond to the assigned class materials and their instructor’s expectations. Nevertheless, this summary tries to provide a simplified description balanced with sufficient detail to enable understanding of the process while being able to use it as a base upon which supplemental information can be added.

Energy Extraction via the Krebs Cycle

Theoretical Yield: 24 Molecules of ATP / Molecule of GlucosePractical Yield: 20 Molecules of ATP / Molecule of Glucose

The Krebs cycle is the primary metabolic pathway through which aerobic energy is released from carbohydrates, proteins, and fats in a useable form. When measuring the energy production of the Krebs cycle, the output is measured in molecules of ATP (Adenosine triphosphate) per molecule of glucose. In total, the theoretical (and typical textbook) yield of cellular respiration (including the Krebs cycle) from one molecule of glucose is 38 molecules of ATP, but in practice the actual yield is closer to 30-32 ATP. Since one molecule of glucose produces two molecules of Acetyl–CoA, the Krebs cycle’s energy output is usually expressed as the product of the two cycles necessary to breakdown both Acetyl–CoA’s. Two Krebs cycles create two GTP, Guanosine triphosphate, which can be readily converted into 2 ATP. The other energy-producing products of the Krebs cycle (NADH, and QH2) theoretically generate an additional 22 ATP, but in practice produce closer to 18 ATP via the mitochondrial electron transport chain. This practical difference results from energy lost from the active transport of various reactants as well as the leakage of electrons within the electron transport chain.

Steps in the Krebs Cycle

The Krebs Cycle releases energy from Acetyl–CoA, but the cellular challenge is to release the energy gradually and in useable forms. So the pathway (1) links the Acetyl-CoA’s acetyl group (2-carbon) to the substrate (4-carbon) to make a 6-carbon molecule; (2) rearranges the 6-carbon molecule to a more reactive form; (3) removes one of the substrate’s carbon molecules to form a 5-carbon molecule and release energy; (4) removes another of the substrate’s carbon atoms, to form a 4-carbon molecule, and release energy; and (5) rearranges the 4-carbon molecule several times to re-create first substrate, releasing energy in the process. The key observation is that the substrate is first manipulated and its carbon atoms are released in the form of CO2, and only then are the atoms in the acetate (from the Acetyl–CoA) rearranged to re-create the substrate.