Request: Kreb's cycle

[Shannon]

I want to understand Kreb's cycle, but don't have the concentration to search out the information. Anyone want to figure it out and post a summary? Here are my questions:

What are all the inputs and where do they come from?
What are the vitamin cofactors?
What are the outputs and what are they used for?
In the most general sense, what are common blockades, and how common are they? (I'm looking for an answer like 'environmental toxins block the XXX loop' or 'there's a common mutation on XXX enzyme that does XXX')

And partial responses are still great, anything is still a part of the puzzle :)

[Nessa]

I actually still have my AP Bio text from HS, I think. It's 11yrs old, but has the krebs cycle changed in that time? (Obviously, I'm being a bit silly.)

I will look at it today during nap time and see what I can gather. I'll probably not be able to post until after bedtime though.

[xekomaya]

For a partial response,

The Kreb's cycle produces almost all the ATP in our bodies, and it does so by using and recycling the NAD+ molecules, which act as electron carriers. Without this, energy is produced by fermentation and produces lactic acid in the body.

Steps of the cycle:
Pyruvic acid and coenzyme A combine to form acetyl CoA, spitting out 1 NADH and CO2. The acetyl coA combines with oxaloacetic acid to form citric acid, which then oxidizes to form CO2. At the same time, NADH is formed leaving ketoglutaric acid. Then the last carbon left from the pyruvic acid is removed to form CO2 and another NADH and 1 ATP is formed. Left behind is succinic acid. The succinic acid releases 2[H] which joins to FAD to form FADH2, leaving malic acid, and again another H is released to form the 4th NADH and the end product of oxaloacetic acid, ready to start the cycle again.

So the final products one one cycle are: 3 CO2, 4 NADH, 1 FADH2, 3 H2O and 1 GTP

A good summary with pictures is found at

http://www.uic.edu/classes/bios/bios100/summer2003/krebsfull.htm

So (trying to understand this myself) the inputs would be the pyruvic acid, cofactors would be H2O, NAD+ and FAD. The outputs are listed above, most significantly the GTP which is readily converted to ATP for use within the body. Blockades would be (I think?) dehydration and suffocation (or whatever that is called within a cell) which would stop the cycle and cause energy to need to be produced by fermentation, causing lactic acid build up/poisoning. Don't know about any mutations - Don't know how long you'd live without your Kreb's cycle...

Does that help a little? If I misunderstood your question or any part of my answer that anyone sees please let me know. Still learning myself.

[Shannon]

Thanks! So the coA is made from pyruvate? I wonder if there are ever any problems with that conversion. And the main purpose is to generate ATP.

And this is what an OAT test is testing, right? That your krebs cycle is working right?

[Nessa]

I have notes in a notebook, but they are incomplete. I'm trying to get a lot of info sorted out in my head right now.

In my understanding... pyruvate plus CoA --> acetyl-CoA. (with CO2 and NADH as by-products). The conversion of pyruvate to CoA is the intermediary step btwn glycolysis and the krebs cycle. From my textbook:

"A protein built into the mitochondrial membrane translocates pyruvate from the cytosol into the mitochondrion. Then (1) the carboxyl group of pyruvate, already fully oxidized, is removed as a CO2 molecule, which diffuses out of the cell. (2) The remaining two-carbon fragment is oxidized while NAD+ is reduced to NADH. (3) Finally, the two-carbon acetyl group is attached to coenzyme A (CoA). The coenzyme has a sulfur atom, which attaches to the acetyl fragment by an unstable bond. This activates the acetyl group for the first reaction of the Krebs cycle."

So: pyruvate in; CO2 out. NAD+ --> NADH. CoA attaches to become acetyl-CoA.

Pyruvate is an end product of glycolysis (glucose, which is a 6-carbon sugar is split into two 3-carbon atoms, which rearrange to form two molecules of pyruvate.) In the presence of O2, pyruvate enters the mitochondrion. (However, glycolysis occurs whether or not O2 is present.)

This link (http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/krebs.htm) shows a fairly detailed pathway from pyruvate to acetyl-CoA. Perhaps a bit TOO detailed, but for the sake of completion and thoroughness I looked. LOL

I was also hoping to find where the CoA comes from.

No ideas about OAT testing...

[xekomaya]

The acetyl-CoA is a building block of both protein and fats, and plants use CoA somehow in photosynthesis so, food in general would be your source. Now, the Kreb's cycle will create energy for the body it seem regardless of where the acetyl-CoA comes from - following glycolosis from pyruvate, or fats and proteins can be broken down to "feed" the cycle. There must be different end products/by products after that happens and I believe that is what is looked for in the OAT test but I would need to read more.

[xekomaya]

This handy chart states more clearly the sources for acetyl-CoA

http://en.wikipedia.org/wiki/File:Catabolism_schematic.svg