Gluconeogenesis occurs in the ___ and ____ in animals
Liver and kidney
Primary function of gluconeogenesis
Maintaining glucose levels in blood
Brain uses __ g glucose per day
120 g
(Can also use ketone bodies when glucose is unavailable)
Glucose can be synthesized from
Non-carbohydrate precursors (gluconeogenic precursors), including:
- Lactate: becomes pyruvate and enters the pathway (reversible rxn from last mod catalyze by lactate dehydrogenase) - lactate from muscles released into blood and taken up by liver to be converted back to pyruvate
- Amino acids: amino acids from diet or protein degaradation become intermediates
- Glycerol: triacylglycerol break down —> glycerol taken up by the liver from the blood —> converted to dihydroxyacetone phosphate
- phosphorylated to glycerol phosphate by glycerol kinase —> glycerol phosphate oxidized to dihydroxyacetone phosphate by glycerol phosphate dehydrogenase
Number of high transfer potential phosphoryl groups spent in synthesizing glucose from pyruvate
6 (4 ATP + 2 GTP)
Overall stoichiometry of gluconeogenesis
2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2H+ + 6 H2O —> glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+
-38 kj/mol
Fructose 1,6-bisphosphatase inhibitors and activators
- Inhibitors: fructose 2,6-bisphosphate and AMP
- Activator: citrate
Pyruvate carboxylase inhibitors and activators
- inhibitor: ADP
- activator: Acetyl CoA
PEP carboxykinase inhibitor
- inhibitor: ADP
Liver responsibility
Maintaining blood sugar levels by adjusting glucose and gluconeogenesis rates
- through F-2,6-Bisphosphate
Fructose 2,6- bisPhosphate
- Activates glycolysis (PFK)
- inhibits gluconeogenesis (F 1,6-bisphosphatase)
- enzymes: PFKase-2 and FBPase-2 (present in the same protein - bifunctional enzyme w two distinct domains - kinase domain and phosphatase domain (also regulatory domain))
Insulin’s effect on gluconeogenesis
Inhibits gluconeogenesis
Insulin
Released by pancreas after a meal to help tissues take up more glucose - inhibits gluconeogenesis (but not in type 2 diabetes - insulin resistance)
Type 2 diabetes
Insulin resistance- body doesn’t respond properly to insulin - produce glucose even when it is enough, leading to hyperglycemia
- sugar increases osmolarity of blood and draws water out of tissues - excessive thirst and frequent urination
- insulin resistance associated w obesity
- drugs target inhibiting liver gluconeogenesis, increasing insulin sensitivity, stimulating ability of pancreas to release insulin
Cori cycle
Lactate to glucose
- Muscle produces lactate from pyruvate after breaking down glucose during strenuous exercise and the absence of oxygen
- lactate released into blood - taken up by liver - converted back to pyruvate using lactate dehydrogenase
- pyruvate converted to glucose by gluconeogenesis
- blood glucose levels replenished, muscle can use this glucose to generate atp via glycolysis again
Gluconeogenesis
The synthesis of glucose from non-carbohydrate precursors
Obligate allosteric activator
An allosteric activator that is required to be beyond to an enzyme for it to have catalytic activity
Reciprocal regulation
A situation where an allosteric molecule inhibits one pathway and activates the opposing pathway, such as that which occurs with glycolysis and gluconeogenesis
