One step in the gluconeogenesis pathway for the biosynthesis of glucose is the partial reduction

One step in the gluconeogenesis pathway for the biosynthesis...

Key Concepts

NADH-Dependent Reduction

NADH-dependent reduction is a process in which NADH serves as a reducing agent by donating electrons and protons to a substrate. In enzymatic reactions, this reduction is vital for converting intermediates into more reduced forms. This reaction typically involves a hydride transfer, and it plays a key role in maintaining redox balance within the cell. The specificity of NADH binding and the subsequent electron transfer is often finely tuned by the enzyme’s active site architecture to ensure efficient catalysis.

Enzyme-Bound Thioester Formation

Enzyme-bound thioester formation involves the covalent attachment of an acyl group to a reactive cysteine residue in the enzyme's active site, forming a thioester intermediate. This step is critical in many biochemical pathways because the thioester linkage is high in energy, which facilitates the transfer of acyl groups in subsequent reactions. The transient nature of this intermediate allows for controlled and directional catalysis, effectively channeling substrates through the metabolic pathway.

Gluconeogenesis

Gluconeogenesis is the metabolic pathway that generates glucose from non-carbohydrate precursors. It is critical in maintaining blood sugar levels during fasting or strenuous exercise. This pathway involves a series of enzymatic reactions that effectively reverse glycolysis, although not all steps are a simple reversal; several unique enzymes and reaction mechanisms are employed to bypass thermodynamically unfavorable reactions.

ATP-Dependent Phosphorylation

ATP-dependent phosphorylation is a reaction where a phosphate group from ATP is transferred to a substrate, activating it for subsequent transformations. In metabolic pathways, this step is essential because it increases the reactivity of the molecule, making it more susceptible to further chemical modifications such as nucleophilic attack. The phosphorylation thus sets the stage for subsequent enzyme-catalyzed reactions, often rendering a normally inert substrate into a high-energy intermediate.

Transcript

00:01 Okay, this problem is asking us to propose a mechanism for the total reduction of three phosphoglycerates into glyceroldehyde 3 phosphate.

00:07 And it is stated that this occurs in three, basically separate steps and the mechanism for all three of those.

00:13 Okay, so i have my three phospholglycerate, which looks like this.

00:18 It is essentially a carboxlate ion, and the carbon is connected to an alcohol, and then connected to another carbon, which is connected to o .p .o .3 -2 -1.

00:29 Okay, so this molecule has a total minus charge of three.

00:34 Okay, so we don't usually see that within organic chemistry, but within biological systems, it's actually pretty commonplace.

00:40 Okay, so i'm going to react this with atp.

00:43 So atp is called adenicine triphosphate.

00:46 It's actually a relatively large molecule, so i'm just going to represent most of it as r.

00:52 So this p that i'm drawing right here is that, i'm going to represent that as the second phosphorus in my total.

00:59 Atp.

01:00 So if it were adp, this would be the final phosphorus.

01:04 But this phosphorus that i'm working on right now is the third phosphorus.

01:11 Okay, so my three -phosphoryte, which is this molecule right here, is going to behave as a nucleophile and attack the third phosphorus, the one of the very right right here, and then it will essentially phosphorylate my three -phosphorylomerate, and in that process, i will create adp.

01:29 So i'm defosphorulating my a .m.

01:30 Atp to make adp and then i'm phosphorylating my three phosphoglycerate.

01:36 Okay, so what i'm doing is i'm moving the electrons from this oxygen onto this phosphorus.

01:43 So this phosphorus is behaving as an electrophile.

01:46 Okay, so when i attack that phosphorus, that phosphorus is exceeding its octet.

01:50 And in reality, phosphorus can actually have more than an octet, but just for this, i'm, i need to remove electrons from it because i'm attacking it with more electrons.

01:58 So i'm going to move the electrons onto this oxygen.

02:02 So if i cut this in half, essentially, which is what i'm doing, i'm making adp.

02:07 So this whole molecule right here is atp.

02:10 I'm defosphoryulating it, so i'm making adp.

02:13 Okay, so after that, i should end up with this, where i have o minus connected to phosphorus, connected to oxygen, connected to an oxygen, and then that is connected to this oxygen.

02:26 So this oxygen is corresponding to this oxygen of my former carboxylate.

02:31 Okay, so that's the oxygen, and it's connected to my carbonyl, and then that is connected to an alcohol, connected to o .p .o .3 -2 -1.

02:45 Okay, so that right there is called 1 -3 bisphosphoglycerate.

02:49 Okay, and then, of course, i made my adp, which i'll just represent quickly right here.

02:58 Okay, so next up, i'm going to react my 1 -3 bisphosphoscelerate right here, and i'm going to react that with a thial group on my enzyme.

03:07 So, again, my enzymes and enzymes in general are actually very, very large molecules.

03:13 So i'm not going to draw out that entire molecule.

03:14 So i'm just going to write down r, which is what they use in the textbook.

03:20 So this style group, my sulfur, sulfur, solfers are actually very good nucleophiles.

03:25 They're actually better nucleophiles than oxygen r.

03:27 So that sulfur is going to attack my carbonyl.

03:32 So it's attacking that carbonyl.

03:33 And when it does that, it's going to move the electrons up to my oxygen.

03:38 Okay, that's pretty standard in carbonyl chemistry.

03:41 I have a nuclei file.

03:42 I attack the carbonyl, and i move the electrons up to the oxygen because the oxygen is considered electronegative.

03:46 Okay, so after that, i should end up with this product.

03:49 And i'll do this step in green, just so we have a little bit of difference.

03:54 Okay, and we're going to make this product in which we have our phosphorus group unaffected.

04:01 I have my oxygen.

04:03 This oxygen corresponds to this one, which is unaffected.

04:05 And then that's going to be connected to my former carbonyl.

04:11 So right now i'm drawing my tetrahedral intermediate.

04:14 So that oxygen now has a negative charge because i move the electrons up to it.

04:17 Sorry, i move the electrons up to it.

04:19 And this carbon corresponds to this carbon.

04:21 That carbon is connected to my thyl group because i just had my sulfur attack it.

04:26 So sulfur with a positive charge because it has a hydrogen.

04:29 And then that is connected to my r group.

04:32 Okay, and then the remainder of my compound.

04:36 So alcohol and then opo3 -2 -2 -1.

04:43 Okay, so what is next? what's next is we have to undergo a proton transfer, or at least just we have to deprotonate my sulfur...

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