Gluconeogenesis
a process whereby organisms can synthesize glucose from non-carbohydrate precursors.
when is gluconeogenesis important
during periods of fasting, intense exercise, or starvation. this is critical since many organs and cells depend on glucose as their primary fuel
what is glucose mainly used for in the body
- red blood cells use glucose as their sole energy source
- The brain is the biggest consumer of glucose (60% of total glucose available)
- muscles use significant amounts of glucose for its energy needs
what can the brain use besides glucose
ketone bodies
where does gluconeogenesis occur
only in liver and kidney, with the liver being the largest contributor as maintaining blood glucose levels is a major function.
how is lactate converted
by the reverse of the reaction of pyruvate to lactate, catalyzed by lactate dehydrogenase.
what are the non-carbohydrate precursors
glycerol, lactate, and some amino acids
how are amino acids converted
some amino acids that are derived from diet or protein degradation, can be metabolized to intermediates in the gluconeogenic pathway, such as oxaloacetate.
how is glycerol converted
triacylglycerols, the form of dat stored in our bodies, can be broken down into fatty acids and glycerol. while fatty acids are used by various organs in our body for fuel, the glycerol that is released from adipose tissue into the blood is taken up by the liver. There, glycerol is converted to dihydroxyacetone phosphate in a two step process
what are the irreversible steps that have to be overcome in gluconeogenesis
pyruvate to phosphenolpyruvate
fructose 1,6 bisphosphate to fructose 6 phosphate
glucose 6 phosphate to glucose
pyruvate to phosphenolpyruvate
pyruvate to oxaloacetate (amino acids can also converted to this) (pyruvate carboxylase) requires ATP
OAA catalyzed to produce phosphoenolpyrivate (PEP carboxykinase) Requires GTP
fructose 1 6 bisphosphate to fructose 6 phosphate
fructose 1,6 biphosphatase (takes off a phosphate, opposite of a kinase) absent hydrolysis of ATP compared to glycolysis
glucose 6 phosphate to glucose
glucose 6 phosphatase used (cleaves off a phosphate)
what enzyme are some people missing
glucose - 6 - phosphatase, causing them to not produce glucose. its also used in the breakdown of glycogen
they are caused to be hypoglycaemic
what is the obligate allosteric activator
Pyruvate carboxylase requires a covalently bound prosthetic group called biotin (derivative of vitamin B7) that carries the CO2 in a manner that facilitates its reactivity with pyruvate. Pyruvate carboxylase also requires that acetyl CoA is bound to the enzyme for it to catalyze carboxylation. In the absence of bound acetyl CoA, carboxylation does not occur. Because of this, acetyl CoA is referred to as an obligate allosteric activator
how is oxaloacetate transported to the cytosol
Oxaloacetate is made inside the mitochondria, but it needs to get to the cytosol to continue the pathway (like in gluconeogenesis).
The problem is:
👉 There is no transporter that can move oxaloacetate across the mitochondrial membrane.
So the cell uses a workaround:
Oxaloacetate is converted into malate inside the mitochondria.
Malate can cross the mitochondrial membrane.
Once in the cytosol, malate is converted back into oxaloacetate.
So basically:
Oxaloacetate can’t leave → turn it into malate → move it out → turn it back into oxaloacetate.
where does glucose 6 phosphatase reside
in the lumen
what is the major point of regulation in glycolysis
The major point of regulation of glycolysis is the conversion of fructose 6-P to fructose 1,6-bisP catalyzed by phosphofructokinase
what is the major point in regulation in gluconeogenesis
The major point of regulation of gluconeogenesis is the step where fructose 1,6-bisP is converted to fructose 6-P catalyzed by fructose 1,6-bisphosphatase.
inhibitors in glycolysis
phosphofructokinase: ATP, Citrate, H+
pyruvate kinase: ATP, Alanine
inhibitors in gluconeogenesis
fructose 1,6 bisphosphatase: F-2, 6-BP , AMP
pyruvate carboxylase and PEP carboxykinase: ADP
activators of glycolysis
PFK: F-2, 6-BP and AMP
pyruvate kinase: F-1, 6 BP
activators of gluconeogenesis
Fructose 1,6 bisphophatase: citrate
pyruvate carboxylase: acetyl coA
cori cycle
During strenuous activity when oxygen may become limiting, muscles produce a significant amount of lactate from pyruvate, which is then released into the blood. Much of this lactate is taken up by the liver, converted back to pyruvate by the enzyme lactate dehydrogenase, and then converted to glucose by the gluconeogenesis pathway.
