Gluconeogenesis

More than glycolysis in reverse: four enzymes bypass the three irreversible steps.

Costs 4 ATP + 2 GTP + 2 NADH per glucose

Bypass enzymes (the First Aid standard)

Pathway Produces Fresh Glucose

Only liver and kidney have glucose-6-phosphatase, which is why muscle can never export glucose and muscle glycogen stays selfish.

Pyruvate Oxaloacetate

Pyruvate carboxylase regulated

“Pathway” → Pyruvate carboxylase

Requires biotin. Activated by acetyl-CoA, the signal that fat is burning and glucose should be spared.

Oxaloacetate Phosphoenolpyruvate

PEP carboxykinase regulated GTP → GDP

“Produces” → PEP carboxykinase

Induced by glucagon and cortisol.

Between here and the last bypass, nothing new is needed: the seven reversible glycolytic enzymes simply run backward. PEP → 2-phosphoglycerate → 3-phosphoglycerate → 1,3-bisphosphoglycerate → glyceraldehyde-3-phosphate, then two trioses condense (aldolase) into fructose-1,6-bisphosphate. This shared stretch is where the 2 ATP (phosphoglycerate kinase) and 2 NADH (GAPDH) per glucose are spent, everything doubled because two three-carbon units build one six-carbon sugar.

Fructose-1,6-bisphosphate Fructose-6-phosphate

Fructose-1,6-bisphosphataserate-limiting

“Fresh” → Fructose-1,6-bisphosphatase

Rate-limiting. Inhibited by AMP and fructose-2,6-bisphosphate, the same two things that activate PFK-1, so the two pathways can never run at once.

Glucose-6-phosphate Glucose

Glucose-6-phosphatase

“Glucose” → Glucose-6-phosphatase

Liver and kidney only. Missing in Von Gierke disease, which is why those patients get fasting hypoglycemia with a big liver.