Chapter 17: Gluconeogenesis

Gluconeogenesis

metabolic pathway that synthesizes glucose from non-carb precursors

essential for maintaining blood glucose during fasting states

occurs in cytosol and mitochondria

spends 6 ATP

Bypass reaction #1&2:

replaces pyruvate kinase

step 1) pyruvate + CO2+ ATP + H2O —> OAA + ADP + Pi + 2H+

enzyme pyruvate carboxylase, mitochondria

step 2) OAA + GTP —> phosphoenolpyruvate + GDP + CO2

enyme: PEPCK, cytosol

rate-limiting + committing step

Malate Aspartate Shuttle

OAA —> Malate —> OAA

OAA is reduced to malate in mitochondria and then oxidized back to OAA in cytoplasm

OAA cannot cross mitochindrial matrix

Bypass Reaction #3

Fructose-1,6-biphosphatase replaces PFK1 (step 3)

F16B —> F6P + Pi

phosphate cleaved (no ATP removed)

Bypass Reaction #4

Glucose-6-phosphotase reverses glucokinase (step #1)

G6P —> glucose + Pi

phosphate cleaved, free glucose released

Energy Cost

Regulation

Hormonal regulation

Cori Cycle

in liver

lactate (anaerobic resp.) —> pyruvate —> glucose —> blood

Type 2 Diabetes

too much glucose production bc liver does not listen to insulin (uncontrolled glycogenesis)

Starvation response (1-3 days)

glycogen depletion so glycogenesis is INCREASED

Starvation Response (post day 3)

ketone body production reduces glucose needs (ketogenesis)

muscle protein sparing as adaptation