From pyruvate to Acetyl-CoA: Oxidation

Captain's Log:

Wow! That glycolysis exercise was a real workout. Molecules switched around so much that I was barely able to meet the atoms in my group before we changed again. When I was one of the lucky carbons that were given the chance to be in pyruvic acid, I was so happy. That means I can continue on my adventure into.... AEROBIC RESPIRATION. Explore new frontiers, meet new electrons, travel into a new dimension, or well, maybe just enter the Krebs Cycle. I was told that before I could enter the Krebs Cycle, our pyruvic acid molecule would have to be oxidized. Even though I was shaking down to every one of my twelve protons, I didn't want to seem naive so I decided to not ask exactly what oxidation would entail. As the time approached for oxidation, I had in mind perhaps laser guns or some sort of battle, but what really happened was a decarboxylation. In simpler terms, one of the carbons in my group left to join an oxygen molecule leaving the rest of us behind. Then, we had been oxidized. I thought that oxidation turned out to be pretty painless after all my worry because I just waited around until coenzyme A came around. It turns out that this molecule is a carrier molecule which means it will carry us into the next phase of our journey, the Krebs Cycle. Well, I better get some rest since I heard that the Krebs Cycle will be quite an adventure!

Overview:

Why would a cell need to continue into aerobic respiration if it could produce two ATP's in glycolysis? The obvious answer to this question is that two molecules of ATP are not much energy for a cell and, as a result, the body evolved to increase their energy production. However, another reason for the necessity of some sort of respiration is the problem that stems from the buildup of NADH. As mentioned in glycolysis, for every pyruvic acid molecule produced from glycolysis, a molecule of NADH is also produced. A problem arises because the cell does not contain much NAD+ and if the cell runs out of NAD+, there is nowhere for G3P (glyceraldehyde 3-phosphate) to donate its extra hydrogen atom and electron. Therefore, through the miracles of evolution, the cell is now able to compensate for this problem through either aerobic or anaerobic metabolism. In anaerobic metabolism, meaning without oxygen, pyruvic acid is changed into lactic acid which eventually causes muscle soreness and fatigue (i.e. sprinting). Since your body can't function for long periods of time without oxygen, the main goal of anaerobic respiration is to recycle NADH from NAD+ so that the product can be used in glycolysis. Fortunately, most of the time an aerobic condition exists where there is oxygen gas present. In aerobic metabolism, the cell takes the extra hydrogen atom and electron from NAD+ and combines it with O2 to form H2O.

A Closer Look:

We left the last process with two molecules of pyruvic acid as a result of the ten-step glycolysis sequence. The oxidation of pyruvic acid to form Acetyl CoA is the first step in aerobic metabolism. First, one of the three carbons of pyruvate splits apart and becomes a part of CO2. This is known as a decarboxylation, where a carbon is attached to oxygen. This leaves behind a pair of electrons with a hydrogen atom and an acetyl group (a two carbon fragment).

Since this reaction is very complex, it needs the aid of a multi-enzyme complex. The complex catalyzes this oxidation by passing the reacting substrate molecule down a line of enzymes. The multi-enzyme complex present in this reaction is pyruvate dehydrogenase, which contains 48 polypeptide chains and is one of the largest enzymes known.

When one of the carbons was oxidized to form CO2, a two-carbon molecule of acetic acid was left behind. In the course of this reaction, a hydrogen and its corresponding pair of electrons are released. These are attached to NAD+ making NADH, an electron carrier that will continue into the Krebs cycle. At the same time, the acetic acid left behind temporarily couples with a carrier molecule called coenzyme A. This acetic acid plus coenzyme A forms a complex named acetyl coenzyme A (acetyl CoA). This new molecule, Acetyl CoA, is extremely important because it can be produced as a result of glycolysis and it can also be made by the breakdown of proteins, fats, and other lipids. Therefore, it does not matter if the body starts with glucose, protein, fat, or lipid, the end result is the same: oxidative metabolism.

Pyruvate + NAD+ + CoA Acetyl-CoA + NADH + CO2
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