Gluconeogenesis
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Gluconeogenesis is the synthesis of glucose. It is basically glycolysis run backwards; three new reactions (involving four new enzymes) make the standard free energy favorable.
- Glycolysis: ΔG′o=−74kcal/mol
- Gluconeogenesis: ΔG′o=−36kcal/mol
For every molecule of glucose synthesized from two molecules of pyruvate, 4 ATP, 2 GTP, and 2 NADH are used.
In the Mitochondria
Pyruvate + ATP → Oxaloacetate + ADP + P
Oxaloacetate + NADH → Malate + NAD+
The conversion to malate allows the molecule to be transported out of the mitochondria. Once in the cytoplasm, it is converted back to oxaloacetate.
In the Cytoplasm
Malate + NAD+ → Oxaloacetate + NADH
Oxaloacetate + GTP → PEP + GDP
From here, it goes through the same intermediates as glycolysis. The last reaction happens in the endoplasmic reticulum.
In the Endoplasmic Reticulum
G6P → glucose (catalyst: glucose-6-phosphatase)
A glucose transporter shuttles the glucose out into the extracellular space.
Regulation
Regulated Reactions | Glycolysis | Gluconeogenesis |
Glucose ⇌ G6P | Hexokinase: G6P (-) | Glucose-6-phosphatase: [G6P] (substrate level control) |
F6P ⇌ F1,6BP | Phosphofructokinase: F2,6BP (+); AMP (+); ATP (-); citrate (-) | Fructose-1,6-bisphosphatase: F26BP (-); AMP (-) |
PEP ⇌ Pyruvate | Pyruvate kinase: F1,6BP (+); acetyl CoA (-); ATP (-); alanine (-); cAMP-dependent phosphorylation (-) | Pyruvate carboxylase: Acetyl-CoA (+) |
These reactions are tightly controlled so that glycolysis and gluconeogenesis are not run at the same time. If they were, the F1,6BP ⇌ F6P reaction could turn into a futile cycle, using up ATP without progressing in either direction.
Glyoxylate Cycle
Plants and bacteria can convert acetyl-CoA to glucose via the glyoxylate cycle. It is a modified version of the TCA cycle; an extra malate is produced which can be converted to glucose. Since animals lack this cycle, they cannot use acetyl-CoA to make glucose because it would stop the TCA cycle.
Starch/Glycogen Synthesis
Glucose is added to chains of glycogen for storage via starch/glycogen synthesis. Glucose is converted to G-6-P, then G-1-P. This is added to UDP, which gives glucose the free energy needed to add to the glycogen. (Plants use ADPG and ATP instead of UDPG and GTP.)
Glucose + ATP → G-6-P + ATP
(catalyst: hexokinase)
G-6-P → G-1-P
(catalyst: P-glucomutase)
UTP + G-1-P → UDPG + PPi
(catalyst: UDPG pyrophosphorylase)
PPi + H2O → 2Pi
The glucose of the UDP-glucose is added to the glycogen chain, leaving UDP.
Pentose Phosphate Pathway (PPP)
The PPP is a source of NADPH, which can be used in reductive anabolic pathways. The PPP can also produce ribose.