citric acid cycle steps

2 min read 13-03-2025

The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a crucial metabolic pathway occurring in the mitochondria of eukaryotic cells and the cytoplasm of prokaryotes. This cycle is central to cellular respiration, playing a vital role in energy production and the metabolism of carbohydrates, fats, and proteins. Understanding its steps is key to grasping cellular energy dynamics.

Step 1: Acetyl-CoA + Oxaloacetate → Citrate

The cycle begins with the entry of acetyl-CoA (a two-carbon molecule derived from pyruvate or fatty acid breakdown) and its combination with oxaloacetate (a four-carbon molecule). This reaction, catalyzed by citrate synthase, forms citrate (a six-carbon molecule). This step is highly exergonic and irreversible under cellular conditions.

Step 2: Citrate → Isocitrate

Citrate is isomerized to isocitrate via aconitase. This involves a dehydration followed by a rehydration step, effectively shifting the hydroxyl group. This step prepares the molecule for the next oxidative decarboxylation.

Step 3: Isocitrate → α-Ketoglutarate + CO2

Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate, releasing one molecule of carbon dioxide (CO2). This step is also highly regulated and produces the first molecule of NADH (nicotinamide adenine dinucleotide), a crucial electron carrier in the electron transport chain.

Step 4: α-Ketoglutarate → Succinyl-CoA + CO2

α-ketoglutarate dehydrogenase complex catalyzes the oxidative decarboxylation of α-ketoglutarate, releasing another molecule of CO2 and producing another NADH molecule. This reaction is very similar to step 3 and also highly regulated. This step is another crucial point in the cycle, generating another high-energy electron carrier.

Step 5: Succinyl-CoA → Succinate

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate. This substrate-level phosphorylation reaction generates one molecule of GTP (guanosine triphosphate), which is readily converted to ATP (adenosine triphosphate). This is the only step in the citric acid cycle that directly produces ATP.

Step 6: Succinate → Fumarate

Succinate dehydrogenase, a membrane-bound enzyme also part of the electron transport chain, catalyzes the oxidation of succinate to fumarate. In this step, two hydrogen atoms are transferred to FAD (flavin adenine dinucleotide), producing FADH2, another electron carrier.

Step 7: Fumarate → Malate

Fumarase catalyzes the addition of water to fumarate, converting it to malate. This hydration reaction is a simple addition of water across the double bond.

Step 8: Malate → Oxaloacetate

Malate dehydrogenase catalyzes the oxidation of malate to oxaloacetate, generating the final NADH molecule of the cycle. This step regenerates oxaloacetate, completing the cycle and allowing it to begin again.

Products of the Citric Acid Cycle

One turn of the citric acid cycle yields:

3 NADH: These molecules donate high-energy electrons to the electron transport chain.
1 FADH2: This molecule also contributes electrons to the electron transport chain.
1 GTP (or ATP): This represents direct energy production.
2 CO2: These are waste products of cellular respiration.

Regulation of the Citric Acid Cycle

The citric acid cycle is tightly regulated to meet the cell's energy demands. Key regulatory enzymes include citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase. These enzymes are inhibited by ATP and NADH, signaling sufficient energy levels, and activated by ADP and NAD+, indicating a need for more energy production.

The Citric Acid Cycle's Significance

The citric acid cycle is a central metabolic hub, connecting carbohydrate, lipid, and protein metabolism. It's vital for generating ATP, the primary energy currency of the cell. Its intermediates also serve as precursors for various biosynthetic pathways, highlighting its importance in overall cellular function. Disruptions to the cycle can have significant consequences for cellular health. Understanding its intricate steps provides a foundation for comprehending numerous metabolic processes and diseases.