Thursday, February 14, 2013

Glucose Metabolism - Glycolysis through Kreb's Cycle

I was trying to think of a way to model these processes for the benefit of kinesthetic learners, so this is what I came up with using these cool toys my kids got from the kids' meal at Wendy's.  I hope this will help people visualize this and understand where all the Carbons from glucose go, and why on earth we care about all those NAD, NADH, FAD, and FADH2.


Here are the symbols for this model.  Purple= Carbon, Blue= Hydrogen, Red=NAD, Green=FAD, Orange=CoA enzyme


Below is a VERY simplified version of a glucose molecule.  This shows the 6 carbons because we want to see what happens to all these carbons.  There should be 12 Hydrogens and 6 Oxygens as well but for simplicity, I have only the carbons and 2 Hydrogens to illustrate one round of Redox reactions in glycolysis.

Glycolysis
Here we start with a glucose molecule and we will break it down.  For this demonstration I am ignoring the ATP, but just note that 2 ATP's go in to Glycolysis and you get 4 ATP out (so, a net production of 2 ATP).

Here are the reactants, or what goes in to glycolysis:



Next, we see that the glucose is broken apart (in half, basically)

And the NAD's come in to take the Hydrogens off to become NADH.  FYI, the glucose was "oxidized" because the electrons were taken off it, and the NAD was "reduced" because it got the electron (the hydrogen).  So, this is a Redox (Oxidation-Reduction) reaction.

Now we have two 3-Carbon structures, and two NADH's


The 3-Carbon moleucles are Pyruvate.

That's the end of glycolysis.  The NADH's are sent on to the electron transport chain at this point, so they leave.  Next the Pyruvates will be taken on and processed further in the next process, sometimes called the "Linking Step".  We will follow one pyruvate - keep in mind this process would happen twice for each glucose molecule since it splits in half into 2 pyruvates.

Oxidation of Pyruvate to Acetyl CoA (aka "The Linking Step")
So here is the Pyruvate going into the linking step.  By the way, this is the point at which metabolism has entered the Mitochondria.  Glycolysis takes place in the cytoplasm, and then pyruvate enters the mitochondria and that is where the rest of the processes take place.


I didn't do an intermediate picture on this one, sorry about that.  The NAD comes and harvests another Hydrogen (which is not shown on my simplified pyruvate), CoA is added and one carbon is removed and disposed of as Carbon dioxide.  Here are the products, notice the 3 Carbons accounted for:



And, we see here where each of the products are headed now:

Kreb's Cycle
Then we follow the Acetyl CoA into the Kreb's Cycle, here are the reactants:


I didn't attempt to show all the steps of the Kreb's cycle here, but there are many redox reactions taking place, turning NAD and FAD into NADH and FADH2.  Here's a diagram of the cycle, if you really want to see it:



 Here you see the products, and see all the carbons are accounted for (2 Carbons in, 2 Carbons out):


And, here are the other products, which are the electron carriers that then deliver it over to the electron transport chain:

Also, note that 1 ATP is made during the Kreb's cycle which is not illustrated.

See this post on the Electron Transport Chain for some great videos about what happens there.  NADH and FADH2 are the carriers that drop off the electrons to run the electron transport chain, which harvests 30+ ATP per glucose molecule.  That is why we care so much about harvesting Hydrogens from glucose so we can make NADH and FADH2 and send them on their merry way to the electron transport chain to make ATP.  ATP is the energy that cells use to do pretty much everything!  If you stop making ATP, you die.  End of story.


So, to sum up - see if you can go through and account for all the Carbons, Hydrogens and Oxygens of glucose (glucose is C6 H12 O6).  You'll see that 6 carbons go in, and 6 carbons come out.  (Remember that each glucose molecule becomes TWO pyruvates, so you would double the numbers from that point on.)

Also, 6 oxygens go in, and how many come out?  Yup, 6.  Go back and check if you want to see for yourself. :)

Now, how about the Hydrogens?  Go through and count to see how many are harvested.  Really, go look and figure it out...


....
Did you come up with 14?  Did you count wrong?  NO!  It is 14.  But there are only 12 on glucose right?  What's the deal?  The reason is we actually have one molecule of water (H2O) that goes in the Kreb's cycle during one of the steps (it's added to fumaric acid to make malic acid), and those are then harvested off.  So there are the extra 2 hydrogens!  :)  It's a beautiful thing.

P.S. if you notice on the diagram of Kreb's, it shows 2 H20 going in, but one of them does come back out, as shown on the more detailed diagram below.  2 water molecules in, 1 back out, that's a net of 1 H20, so there are your extra 2 Hydrogens still.  I circled the H20 for you to see:
Source

Hope that helps you understand and visualize metabolism better!  I'd love if you would leave a comment, and follow this blog if you feel so inclined.  Thanks, and happy learning. :)

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