Gluconeogenesis Flashcards
where does gluconeogenesis occur and why?
Mostly in the liver, with a small amount taking place in the kidney. These are the only two organs that can dephosphorylate glucose-6 phosphate. Liver is the major regulatory organ for glucose because it is where glycogen is stored.
what happens in gluconeogenesis?
pyruvate is converted into glucose. lactate, some amino acids, and glycerol are converted into pyruvate for conversion to glucose. This is an energy-requiring pathway.
how is alanine used as a substrate?
alanine can be converted to pyruvate through a transamination reaction. Swap an amino group (alanine) for a carbonyl (pyruvate).
why is gluconeogenesis not a direct reversal of glycolysis?
There are 3 irreversible enzyme steps in glycolysis. Gluconeogenesis must work around these three steps. They are the steps with hexokinase, phosphofructokinase, and pyruvate kinase.
what are the steps in gluconeogenesis used to bypass the irreversible steps of glycolysis?
- PEP is formed from pyruvate by way of oxaloacetate. Carboxylate pyruvate using pyruvate carboxylase to form oxaloacetate. Then you decarboxylate oxaloacetate, which provides the energy needed to attach a free phosphate onto to generate PEP.
a. Pyruvate + CO2 + ATP + H2O –> (Pyruvate carboxylase) oxaloacetate + ADP + Pi
b. Oxaloacetate + GTP –> PEP + GDP + CO2
(phosphoenolpyruvate carboxykinase)
- fructose 6-phosphate is formed from fructose 1,6-bisphosphate by another phosphatase enzyme (fructose 1,6-bisphosphatase).
Fructose 1,6-bisphosphate + H2O–> fructose 6-phosphate + Pi
(fructose 1,6-bisphosphatase) - Glucose is formed by the hydrolysis of glucose 6-phosphate in a reaction catalyzed by glucose 6-phosphate
Glucose 6-phosphate + H2O –> glucose + Pi
(glucose 6-phosphatase)
where does gluconeogenesis begin?
mitochondria. Pyruvate –> oxaloacetate occurs in mitochondria. Then oxaloacetate is converted to malate to be shipped out to the cytoplasm and is reconverted into oxaloacetate.
biotin
a vitamin cofactor for pyruvate carboxylase (the enzyme that changes pyruvate to oxaloacetate). It is a covalently attached prosthetic group that serves as a carrier of activated CO2 (readily donates the CO2 to other molecules). Biotin is not carboxylated unless acetyl CoA is bound to the enzyme.
oxaloacetate gets shuttled to the cytoplasm because…
gluconeogenesis begins in the mitochondria, where pyruvate is converted to oxaloacetate by pyruvate carboxylase. The rest of the enzymes needed for gluconeogenesis exist in the cytoplasm. But there is no transporter for oxaloacetate in the mitochondrial membrane, so it is converted to malate, which does have a transporter. Malate is transported out to cytoplasm and reconverted to oxaloacetate to finish the pathway.
what are the enzyme steps different in gluconeogenesis than glycolysis?
- pyruvate carboxylase (carboxylation of pyruvate to form oxaloacetate)
- phosphoenolpyruvate carboxykinase (decarboxylation of oxaloacetate provides energy to attach a phosphate and form PEP)
- fructose bisphosphatase removes one phosphate (PFK cannot be reversed)
- glucose 6-phosphatase removes the other phosphate (hexokinase cannot be reversed)
glucose 6-phosphatase
this enzyme is only found in the liver and kidneys. This enzyme is found in the lumen of the ER. This enzyme takes the phosphate off of glucose, which is added by every cell when glucose enters the cell so it can’t leak out. But the liver stores glucose and wants the ability to let glucose back out of the cell to other parts of the body.
overall reaction of gluconeogenesis
2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 6H2O –> glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+
how is lactate used as a substrate in gluconeogenesis?
It taken from the muscles and transported to the liver through the blood stream. In the liver, it is converted to pyruvate
Cori Cycle
Lactate is taken from the muscles and transported to the liver through the blood stream. In the liver, it is converted to pyruvate and subsequently glucose via gluconeogenesis. Then the glucose can be sent back to muscles via blood. This whole cycle is known as the Cori cycle.
