Glycolysis/Kreb's Cycle

[evusq]

I am confused about the link between glycolysis and Kreb's cycle. I know that glycolysis takes place in cytoplasm and that it turns glucose into two molecules of pyruvate. And Kreb's cycle takes place in matrix, starting with acetyl CoA. So where does the reaction of turning pyruvate to acetyl CoA take place?

Also, does glucose enter the cell by facilitated diffusion? Glucose needs a transport protein, as in the case of sodium/glucose symport, but it sounds like it sometimes diffuses down the concentration?? And from cytoplasm to cross the membranes of matrix, does it first cross the outermembrane through a pore and then a transporter protein in inner membrane? But since glucose goes through glycolysis first, it only gets to mitochondria in the form of pyruvate? Some of this might be too detailed but I'm confused, and I don't even know with what exactly.

Thanks so much for your help!

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[PiBond]

The pyruvate dehydrogenase complex changes pyruvate into acetyl-CoA in the matrix. PDC is a set of 3 enzymes that oxidatively decarboxylates pyruvate and changes it from a 3-carbon molecule to a 2-carbon molecule. The acetyl-CoA then enters the Krebs cycle for further oxidation.

Quick rundown--assuming aerobic respiration:
Glycolysis takes place in cytoplasm and produces 2 pyruvates per glucose molecule.
Pyruvate is transported to mito matrix and enters PDC. Pyruvate is oxidatively decarboxylated to acetyl-CoA.
Acetyl-CoA enters Krebs for further oxidation. Both the Krebs and PDC occur in the same place, the mitochondria matrix.
While all of the above is occuring, there are electron carriers (NADH and FADH2) that are accumulating (mostly from Krebs). These end up transferring their electrons to proteins embedded in inner mito matrix in the electron transport chain. Protons are pumped across the inner mito membrane when the high energy electrons are transferred from protein-to-protein and this creates the proton gradient (source of potential energy) to drive ATP synthase.

hope that helps

I am confused about the link between glycolysis and Kreb's cycle. I know that glycolysis takes place in cytoplasm and that it turns glucose into two molecules of pyruvate. And Kreb's cycle takes place in matrix, starting with acetyl CoA. So where does the reaction of turning pyruvate to acetyl CoA take place?

Also, does glucose enter the cell by facilitated diffusion? Glucose needs a transport protein, as in the case of sodium/glucose symport, but it sounds like it sometimes diffuses down the concentration?? And from cytoplasm to cross the membranes of matrix, does it first cross the outermembrane through a pore and then a transporter protein in inner membrane? But since glucose goes through glycolysis first, it only gets to mitochondria in the form of pyruvate? Some of this might be too detailed but I'm confused, and I don't even know with what exactly.

Thanks so much for your help!

 

[BennieBlanco]

I am confused about the link between glycolysis and Kreb's cycle. I know that glycolysis takes place in cytoplasm and that it turns glucose into two molecules of pyruvate. And Kreb's cycle takes place in matrix, starting with acetyl CoA. So where does the reaction of turning pyruvate to acetyl CoA take place?

Also, does glucose enter the cell by facilitated diffusion? Glucose needs a transport protein, as in the case of sodium/glucose symport, but it sounds like it sometimes diffuses down the concentration?? And from cytoplasm to cross the membranes of matrix, does it first cross the outermembrane through a pore and then a transporter protein in inner membrane? But since glucose goes through glycolysis first, it only gets to mitochondria in the form of pyruvate? Some of this might be too detailed but I'm confused, and I don't even know with what exactly.

Thanks so much for your help!

Lol, just had an exam on this.

What pibond said was all correct. I will also throw in my 2 cents.

The PDC conversion of pyruvate to acetyle CoA does occur inside the mitochondria matrix.

What you call the Kreb's cycle I call the citrate cycle.

How does glucose enter the cell? this is beyond the MCAT knowledge but I will answer. This is off memory so be kind.

There are 5 glucose transport proteins, Glut-1, Glut-2, Glut-3, Glut-4, Glut-5. Different cells have different types of glucose transporters. (I had to look at some notes real quick), Glut 1 is in many tissues, Glut 2 is a high capacity transporter in hepatocytes, pancreatic beta cells, intestine and kidney, Glut 3 is in neurons, Glut 4 is in muscle and fat cells, and glut 5 deals with fructose transport. As you can imagine, each different type of glucose transport has a different affinity and transport process, some allow a ton of glucose to flow in and others are more selective.

The MCAT is not going to expect you to know this much detail. My endocrine physiology class didn't go in to much more detail that I have mentioned above. In muscle cells the Glut 4 transport to the membrane upon signaling from insulin and then allow glucose to move down the concentration gradient rather rapidly. While in liver cells I believe the Glut 2 transporters are available all the time (also in the kidney).

You won't need to know this much. When no one clearly says glucose transports like _____, it is likely because each specialized cell will have different pathways that involve transport. In the MCAT we learn cell biology of a generic cell, in real life each cell has its own thing going on.

E.g. Red blood cells have NO mitochondria. Therefore they don't even use the ETS or ETC. Specialized cells in real life.

It is interesting to learn about how things actually work instead of having everything dumbed down and summarized though.

 

[RogueUnicorn]

citrate cycle is a bad name for TCA/krebs, as it is confusing with another citrate cycle used to export AcetylCoA for fatty acid & cholest. synthesis

 

[BennieBlanco]

citrate cycle is a bad name for TCA/krebs, as it is confusing with another citrate cycle used to export AcetylCoA for fatty acid & cholest. synthesis

actually it isn't a bad name. My biochem professor who is a biochem nerd and has been writing a biochem text book for 9 years on weekends insists that we use the word "citrate" instead of "citric acid cycle" on the basis that citric acid doesn't exist at physiological pH and only citrate does.

He always says he has no idea why people call it the citric acid cycle when it doesn't exist at physiological pH. The guy is very into biochem. It's like a hobby for him.

I just listen to him because he knows this stuff pretty well.

 

[BennieBlanco]

citrate cycle is a bad name for TCA/krebs, as it is confusing with another citrate cycle used to export AcetylCoA for fatty acid & cholest. synthesis

plus is that a cycle? I just had an exam on this, as I understand citrate just exports to the cytosol and can be converted back to acetyl CoA and OAA freeing up the OAA for amino acid synthesis/gluconeogenesis and the acetyl CoA for FA or chol synthesis. It is just a one step conversion done by one enzyme (citrate ______ase) I can't remember. Lyase? ... i don't know.

 

[RogueUnicorn]

um.. my point had nothing to do with the citrate vs citric acid minutiae, but i have to wonder whether that's a sound argument. to say it's the synthesis of citrate would imply there was no formation of the acid to begin with, when in fact it's a synthesis of acid followed by deprotonation. also, at any pH, there is bound to be all forms of an acid.

 

[RogueUnicorn]

plus is that a cycle? I just had an exam on this, as I understand citrate just exports to the cytosol and can be converted back to acetyl CoA and OAA freeing up the OAA for amino acid synthesis/gluconeogenesis and the acetyl CoA for FA or chol synthesis. It is just a one step conversion done by one enzyme (citrate ______ase) I can't remember. Lyase? ... i don't know.

it's citrate --> OAA + AcCoA, OAA + NADH-->Malate + NAD, Malate +NADP --> Pyruvate + NADPH, and the pyruvate goes back to the mitochondria to recondense into citrate.

 

[BennieBlanco]

um.. my point had nothing to do with the citrate vs citric acid minutiae, but i have to wonder whether that's a sound argument. to say it's the synthesis of citrate would imply there was no formation of the acid to begin with, when in fact it's a synthesis of acid followed by deprotonation. also, at any pH, there is bound to be all forms of an acid.

I'm just learning dude, you probably know more than me.🙂

I started this premed thing a year ago. I'm by far not an expert, but I try to learn from the experts. I guess the point he was making is that citrate is the molecule used in the cycle (at physiological pH in the cells) rather than citric acid. So although there may be some citric acid, because of the abundance of citrate it should be in the name.

Live and learn. Who knows.

 

[BennieBlanco]

it's citrate --> OAA + AcCoA, OAA + NADH-->Malate + NAD, Malate +NADP --> Pyruvate + NADPH, and the pyruvate goes back to the mitochondria to recondense into citrate.

agreed... but the reason for the export was to make the FA or chol (or gluconeogenesis of OAA) so it isn't really a cycle because the export has a metabolic fate, correct? Why export the citrate if it is necessary inside the mitochondria?

 

[RogueUnicorn]

I'm just learning dude, you probably know more than me.🙂

I started this premed thing a year ago. I'm by far not an expert, but I try to learn from the experts. I guess the point he was making is that citrate is the molecule used in the cycle (at physiological pH in the cells) rather than citric acid. So although there may be some citric acid, because of the abundance of citrate it should be in the name.

Live and learn. Who knows.

it's true it's mostly citrate. but again, i think the trend now is to call it the TCA (tricarboxylic acid cycle) since that's how all my profs from ugrad-->smp are calling it. who knows really.

agreed... but the reason for the export was to make the FA or chol (or gluconeogenesis of OAA) so it isn't really a cycle because the export has a metabolic fate, correct? Why export the citrate if it is necessary inside the mitochondria?

it's a cycle because it goes in a cycle. only a part has a metabolic fate, like the TCA cycle. the citrate has to be exported because there's just no other way to get acetyl CoA out of the matrix.

 

[BennieBlanco]

it's true it's mostly citrate. but again, i think the trend now is to call it the TCA (tricarboxylic acid cycle) since that's how all my profs from ugrad-->smp are calling it. who knows really.




it's a cycle because it goes in a cycle. only a part has a metabolic fate, like the TCA cycle. the citrate has to be exported because there's just no other way to get acetyl CoA out of the matrix.

well played.

everyday I learn a bit more. My brain will likely explode in 5 years after medical school.

 

[BennieBlanco]

plus I must say, I enjoy reading your posts in the pre-Allo forum when the arrogant freshman run amuck.

 

[RogueUnicorn]

plus I must say, I enjoy reading your posts in the pre-Allo forum when the arrogant freshman run amuck.

it's an interesting experience considering i could easily have been one of them in my own teenaged youth as well..

 

[BennieBlanco]

it's an interesting experience considering i could easily have been one of them in my own teenaged youth as well..

Fact: I was one of them. lol

Just part of life, I have to work against it everyday.