The hydrolysis of a biological thioester to the corresponding carboxylate is often more complex

The hydrolysis of a biological thioester to the...

Key Concepts

Substrate-Level Phosphorylation

Substrate-level phosphorylation is a process where a phosphate group is directly transferred from a phosphorylated intermediate to a nucleotide, forming high-energy nucleoside triphosphates like ATP or GTP. This mechanism is crucial in metabolic cycles, providing a direct means of synthesizing energy-rich compounds without the need for an electrochemical gradient.

Nucleophilic Attack Mechanisms

Nucleophilic attack mechanisms are central to many biochemical reactions, including acyl transfer and phosphate group exchange. In these processes, a nucleophile targets an electrophilic center, such as a carbonyl carbon, leading to the formation of an intermediate that can then resolve to yield a product. This fundamental concept is key to understanding stepwise enzyme-catalyzed reactions in metabolic pathways.

Acyl Phosphate Intermediates

Acyl phosphate intermediates are high-energy compounds formed when a phosphate group reacts with an acyl compound. These intermediates serve as key evolutionary surrogates to store and transfer energy, allowing for subsequent reactions that generate energy-rich phosphate bonds. Their formation is a common strategy in metabolism to facilitate the transfer of acyl groups.

Biological Thioesters

Biological thioesters are activated forms of carboxylic acids in metabolic processes. Their high energy of hydrolysis results from the relatively unstable linkage between the acyl group and the thiol, making them effective acyl group donors in biochemical reactions. This reactivity is exploited in various metabolic pathways to drive energetically unfavorable reactions.

Transcript

00:01 Okay, this problem is asking us to show the mechanism of hydrolysis of a biological thioester.

00:04 Okay, so if we are undergoing hydrolysis with a biological thioester, we should end up with a carboxlate ion.

00:10 Okay, so for this specific problem, we are dealing with succino -coa, and we are ending up with a succinate.

00:16 Okay, so here is my succino coenzyme a.

00:19 It looks something like this.

00:21 So we have our co -enzyme a connected to sulfur.

00:24 That is going to be connected to a carbonyl, and then we have the rest of our carbon chain.

00:27 And then a carboxylate ion on this side.

00:32 Okay, so normally with hydrolysis, we are dealing with either a hydroxide ion coming in and attacking a carbonyl to eventually lead to the hydrolysis of a molecule or even water, perhaps, but in biological systems, we don't necessarily have to have those reactions.

00:47 Instead, we can react it with a phosphate group.

00:51 Okay, so in biological systems, phosphate groups like this are present in large amounts, either through atp, through inorganic phosphates, inner body, etc.

01:02 But nonetheless, we're going to attack using our oxygen as a nucleophile.

01:06 We're going to attack this carbonyl.

01:09 So when i attack that carbonyl, my phosphate group is behaving as a nuclei, and my carbonyl is behaving as the electrophile.

01:16 And the reason for that electrophilic carbon is because, in reality, this carbon is connected to an oxygen.

01:22 Oxygen is much more electronegative than carbon, so electrons are going to want to go onto this oxygen.

01:28 So if electrons are going onto that oxygen, that auction is going to end up with a negative charge, and we're going to have a positive charge left on my carbon.

01:34 So if i have a positive charge on my molecule and i have a nucleophile, that nucleophile is going to attack that positive charge.

01:41 It's going to attack that carbon that has the positive charge.

01:43 So that is why i'm attacking that carbonyl.

01:45 Okay, so as for my reaction, i'm going to attack that carbonyl and end up with this product.

01:52 In which i have coenzyme, sulfur, unaffected.

01:55 I have my carbon connected to my oxygen.

01:59 So this oxygen right here is this oxygen right here.

02:02 Okay, so this is my tetrahedral intermediate, which i'm about to draw.

02:06 Okay, my third point is my oxygen, which is connected to my hydrogen and phosphorus group.

02:13 So this right here is what i just used to attack my carbonium.

02:17 Okay, and the next step, i'm going to draw out the remainder of my molecule, which is this part.

02:22 So that is this and then this.

02:27 Okay, so here we see that.

02:28 That we have a positive charge on my phosphate group and this negative charge of my oxygen.

02:34 So whenever we see this, obviously, we do not necessarily like negatives and positive charges if we can end up making the molecule neutral.

02:41 So normally we would see a deprotonation of this hydrogen and then eventually put it onto this negatively charged oxygen.

02:48 But in this case, it might be a little bit different because we have to think about what is the future of our reaction.

02:54 Our future is we're going to reform my carbonyl.

02:57 So i'm going to eventually move the electrical from this oxygen down making a carbonyl, this carbon will exceed its octet, so i need to move the electrons away from that carbon.

03:06 Okay, so i need to figure out what is going to be my leaving group.

03:10 I have three options here.

03:11 So i already know that the electrons are going to come down from this oxygen for my carbonyl, so this auctione.

03:15 So this auction is not going to be part of my leaving group.

03:17 So i'm not going to want to protonate it because it's not going to be a potential leaving group.

03:22 I want to keep it as a regular oxygen.

03:24 Okay, so i have three options.

03:25 Either i can make this one leave.

03:27 If i make that one leave, let's think.

03:29 If i make that one leave, i'm going to be back to where i started, right? i'm going to end up with both of these molecules...