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Hello I am studying to be a vet and have just done an experiment on Gluconeogenesis looking at the different precursors. I am a bit stuck on why lactate and alanine might be of different efficiency as gluconeogenic substrates, because they are both converted into pyruvate?? Lactate appears to be more efficient at glucose production in a starved rat kidney. why is this ?
if anyone knows at all it would be much appreciated!
well Lactate dehydrogenase catalyses lactate to pyruvate buut we haven't been taught about the conversion of alanine to pyruvate so i don't know... is it anything to do with amino acids being used by the body during starvation and lactate produced from muscles being removed from the blood by gluconeogenesis?
I'm not too sure, but it may be because gluconeogenesis from amino acids is less favorable than lactate.
The [delta]G of L-Lactate to Pyruvate is 25.1, so it's energetically unfavorable. However, to turn lactate into pyruvate, all you need to do is oxidize the hydroxyl group at the C2 carbon.
On the other hand, Alanine needs to be deaminated via Alanine transminase, that uses PLP as a cofactor to transfer the amino group to a-ketoglutarate. Alanine then needs to be hydrolyzed and oxidized to yield Pyruvate.
It's probably simpler and more energetically favorable to oxidize lactate, than to deaminate, hydrolyze, and oxidize alanine to yield the same product.
Some small amount of glucose may be found in your cells with no substrate from gluconeogenesis of residual metabolic intermediates? Acetyl-CoA, Oxaloacetate, malate, PEP or isomerization from fructose?
Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of kidneys.
The process is highly endergonic until ATP or GTP are utilized, effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP. Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also a target of therapy for type II diabetes, such as metformin, which inhibits glucose formation and stimulates glucose uptake by cells.
Last edited by JackBean on Fri May 31, 2013 11:56 am, edited 1 time in total.
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Liver is a very important versatile organ for mammals.
Gluconeogenesis from lactate is very easy as the lactate is the end product of anerobic glycolysis.
Gluconeogenesis from alanine is realtively difficult as the 'N' must be removed as urea.
In gluconeogeneis there is no "net" calorie production but a survival meachanism for brain and muscles.
In alanine, additional energy should be spent over deaminase, urea synthesis and excretion.
Kidneys may lack these enzymes or lesser efficient isoforms, subcellular oragnaells than liver.
The extra energy spent for nitrogen removal is the "gap" in efficiency.
The nitrogen build up is more toxic to cells, so the cycle of alanine to glucose is very difficult.
kidney < liver
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