Glycolysis and the Citric Acid Cycle
Glycolysis and the citric acid cycle are the central catabolic pathways that oxidize glucose-derived carbon, capturing energy as ATP and reduced electron carriers.
Definition
Glycolysis is the cytosolic pathway that converts one glucose to two pyruvate with net production of ATP and NADH; the citric acid cycle is the mitochondrial pathway that oxidizes the acetyl group of acetyl-CoA to carbon dioxide, generating NADH, FADH2, and GTP.
Scope
This topic covers the ten reactions of glycolysis from glucose to pyruvate, the oxidative decarboxylation of pyruvate to acetyl-CoA, and the eight reactions of the citric acid cycle, including their net energy yield, their key regulated steps, and their roles as both energy-yielding and biosynthetic precursor-supplying pathways.
Core questions
- What are the energy-investment and energy-payoff phases of glycolysis?
- How is pyruvate linked to the citric acid cycle?
- What are the net products of one turn of the citric acid cycle?
- Which steps are regulated and why?
Key theories
- The citric acid cycle
- Krebs deduced a cyclic series of reactions that regenerates oxaloacetate while oxidizing acetyl units, explaining how cells fully oxidize carbon fuels and reduce electron carriers for downstream ATP synthesis.
Mechanisms
In glycolysis, glucose is phosphorylated and split into two three-carbon units that are oxidized and dephosphorylated to pyruvate, yielding a net two ATP and two NADH by substrate-level phosphorylation. Pyruvate dehydrogenase converts pyruvate to acetyl-CoA. In the citric acid cycle, acetyl-CoA condenses with oxaloacetate; successive oxidations and decarboxylations release two carbon dioxide molecules and produce three NADH, one FADH2, and one GTP per turn while regenerating oxaloacetate.
Clinical relevance
These pathways are the canonical examples of metabolic reaction networks studied in chemistry and metabolic engineering; their intermediates also feed biosynthesis. The treatment is descriptive and non-prescriptive.
History
Glycolysis was elucidated in the 1930s by Embden, Meyerhof, and Parnas, after whom the pathway is sometimes named; Krebs published the citric acid cycle in 1937, completing the picture of how fuels are oxidized to carbon dioxide with conservation of energy in reduced cofactors.
Key figures
- Hans Krebs
- Gustav Embden
- Otto Meyerhof
- Jakub Karol Parnas
Related topics
Seminal works
- krebs1937
- nelson2021
Frequently asked questions
- Does glycolysis require oxygen?
- No; glycolysis itself is anaerobic, producing pyruvate, ATP, and NADH without oxygen, though the fate of pyruvate and the reoxidation of NADH depend on whether oxygen is available.
- Why is the citric acid cycle called a cycle?
- Because its final reaction regenerates the starting molecule oxaloacetate, allowing the pathway to accept another acetyl group and run continuously.