fructose 1,6-bisphosphate
Summary
Fructose 1,6-bisphosphate is the six-carbon glycolytic intermediate formed when PFK-1 uses ATP to phosphorylate fructose 6-phosphate, the committed step. Aldolase then splits it into DHAP and glyceraldehyde 3-phosphate. Gluconeogenesis bypasses PFK-1 using fructose 1,6-bisphosphatase.
Detail
Meaning: Fructose 1,6-bisphosphate carries separate phosphate groups on C1 and C6. In glycolysis it forms when phosphofructokinase-1 (PFK-1) transfers a phosphate from ATP to fructose 6-phosphate. This is the committed, rate-limiting step, and it is strongly exergonic, so it is effectively irreversible in the cell. Aldolase then cleaves the molecule into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). Triose phosphate isomerase interconverts these two, so one glucose gives two G3P. In gluconeogenesis, fructose 1,6-bisphosphatase hydrolyzes the C1 phosphate to give fructose 6-phosphate and Pi, bypassing PFK-1.
On the MCAT: Passages usually test regulation and direction of flux. PFK-1 is inhibited by ATP and citrate and activated by AMP and fructose 2,6-bisphosphate. Fructose 1,6-bisphosphatase is inhibited by AMP and fructose 2,6-bisphosphate. Expect questions on which steps are irreversible, what happens to intermediates when one enzyme is inhibited, and ATP accounting (two ATP are invested before cleavage, so the pathway is net-positive only later). Fructose 1,6-bisphosphate also activates pyruvate kinase, a feedforward effect.
Common confusion: Do not mix it up with fructose 2,6-bisphosphate. The 2,6 compound is not a glycolytic intermediate. It is a regulator made by PFK-2 and it controls PFK-1 and fructose 1,6-bisphosphatase.
Sources
- Lehninger Principles of Biochemistry
- Biochemistry (Berg, Tymoczko, Gatto, Stryer)
- Biochemistry (Voet and Voet)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.