Gluconeogenesis

[beckyacoles]

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!

[JackBean]

The easiest thing will be to blame the compound(s), which is/are necessary for conversion of your substrate to pyruvate.

[beckyacoles]

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?

[beckyacoles]

or perhaps that a by-product of energy production from alanine is urea and removal of this uses energy? ahhh so confused!

[beckyacoles]

Also, there was production of some glucose in the control flasks with no substrate in them....why would this be??

[bytesyzechic]

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?

[JackBean]

what do you need to hydrolyse and oxidise in alanine to get pyruvate? :-/