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The Krebs cycle consists of eight interconnected reactions that take place in nearly all living cells to generate energy. During this process, carbon dioxide is expelled, one ATP molecule is synthesized, NADH+ is converted into NADH (three molecules), and FADH2 is produced from FAD. Wikimedia Commons (CC By SA 4.0)At this very moment, your body is the stage for incredibly complex biochemical processes.
For your body to perform even the simplest tasks — whether it's bouncing on a trampoline, walking to the bathroom, or moving your eyes as you read this article — it relies on cellular respiration. This process allows your cells to convert the oxygen you inhale and the food you consume into usable energy.
As you might guess, transforming a peanut butter and jelly sandwich into the energy for a pushup isn't straightforward. Let's explore how the Krebs cycle performs this biochemical marvel.
Cellular Respiration
A primary objective of cellular respiration is to generate ATP, or adenosine triphosphate, a specialized form of stored energy. Consider ATP the universal energy currency of your cells. While sunlight is energy, it can't fuel our bodies directly because it doesn't align with the energy language our systems recognize — animal bodies exclusively operate on ATP.
A crucial stage in the journey from sandwich to pushup is the Krebs cycle, also referred to as the citric acid cycle (CAC) or tricarboxylic acid cycle (TAC), named after Hans Krebs. He was the pioneer who deciphered this biochemical process in 1937, earning him the Nobel Prize in Physiology or Medicine in 1953.
This recognition was well-deserved, as the Krebs cycle is remarkably intricate, utilizing shifts in chemical bonds to reconfigure energy.
The Krebs cycle occurs within our cells, specifically across the inner membrane of the mitochondria — the organelles tasked with generating cellular energy.
Cellular respiration is a multi-stage process that begins with glycolysis, where glucose, a six-carbon compound, is broken down into three-carbon molecules known as pyruvic acids and two energy-dense compounds called NADH. From this point, the Krebs cycle takes over.
The Krebs Cycle
The Krebs cycle is an aerobic process, meaning it relies on oxygen to function. Alongside oxidative phosphorylation, the Krebs cycle immediately begins combining carbon and oxygen in the respiration pathway.
"Initially, two carbon atoms enter the cycle, and two carbon atoms are oxidized and expelled from the cycle," explains Dale Beach, a professor in the Department of Biological and Environmental Sciences at Longwood University in Farmville, Virginia.
"We can consider this initial step as the final oxidation of glucose sugar. If we track the carbons, six entered the respiration pathway during glycolysis, and six must ultimately exit. While these aren't the exact same six carbons, this process underscores the transformation of glucose into carbon dioxide through the pathway."
One carbon from the three-carbon molecule bonds with an oxygen molecule, exiting the cell as CO2. This results in a two-carbon molecule known as acetyl coenzyme A, or acetyl coA. Subsequent chemical reactions rearrange the molecules, oxidizing the carbons to produce additional NADH and FADH.
The Roundabout
Following the respiration pathway, the Krebs cycle enters a second oxidation phase, resembling a traffic roundabout, which gives it its cyclical nature. The acetyl coA merges with oxaloacetate to create citrate synthase, leading to the name "Krebs cycle."
This citric acid undergoes oxidation through multiple steps, losing carbons as it progresses around the roundabout until oxaloacetic acid is reformed by the oxidation of malate. As carbons are released from the citric acid, they convert into carbon dioxide molecules, expelled from the cell and eventually exhaled by the body.
Energy Generation and CoenzymeA
"In the second oxidation phase, a high-energy bond forms with the sulfur of CoA, resulting in Succinate-CoA," explains Beach. "This bond contains sufficient energy to directly generate an ATP equivalent; GTP is produced instead, but it holds the same energy level as ATP — a unique characteristic of this system."
"The detachment of CoenzymeA leaves behind a Succinate molecule. From this stage, a sequence of steps reorganizes chemical bonds and introduces oxidation events to regenerate the original oxaloacetate. Throughout this process, the pathway generates a low-energy FADH molecule and a final NADH molecule," Beach adds.
Implications and Evolutionary Insights
For every glucose molecule entering respiration, the roundabout can complete two cycles, one for each pyruvate. However, it isn't mandatory for the cycle to run twice, as cells can divert carbons for other macromolecules or introduce additional carbons by breaking down amino acids or utilizing energy stored in fats.
As you can see, the biochemistry is intricate. Beach highlights that a key feature of the Krebs cycle is the recurring presence of adenosine — found in NADH, FADH, CoenzymeA, and ATP molecules.
"Adenosine acts as a 'molecular handle' for proteins to latch onto. It's plausible that ATP binding pockets evolved to be reused, creating binding sites for other molecules with similar structures."
For every glucose molecule we consume, our cells can generate 38 ATP molecules, along with a small amount of heat energy.
