Metabolism and the Production of ATP

Moving about, pumping blood, producing complex cellular structures, transporting molecules – these and other everyday activities that we normally take for granted all extract a price: they require energy. That energy is supplied by food. On the one hand, we have the machines that do the work (muscles for example); on the other hand, we have the food as an energy source. Somehow they must be linked; energy has to be extracted from the food and stored in a form that is directly utilizable by the machine. The primary storage form living organisms use in the molecule ATP (adenosine triphosphate). ATP contains three phospate groups joined in tandem. When the terminal phosphate is split off, it becomes ADP (adenosine diphosphate), and considerable energy is released. If the proper machinery is present, most of this energy can be captured and used for work. The ADP is not a simple waste product; it is recycled and utilized to synthesize new ATP.

ATP——- ADP +P+ energy (energy from work goes toward the right), (energy from food goes toward the left)

The reaction goes to the right to power cellular machinery for contraction, transport, and synthesis. But if the split phosphate group is simply transferred to water, this energy is wasted: it is given off as heat. However, if the phosphate is transferred to the machine, the energy goes with it, and the machine becomes energized. (The molecular part of the machine that receives the phosphate now has a higher energy content, which allows it to enter reactions it otherwise could not have entered. The finer details of how the actual machinery works are not understood.) ATP is the universal energy currency because of its ability to phosphorylate (transfer the phosphate to) cellular machines and boost them into a higher energy state.

The reaction goes to the left as carbohydrates, fats, and proteins are broken down by chemical reactions occurring with the cell (metabolism). Glucose contains large quantities of energy that can be released when the chemical  bonds holding its atoms together are broken. For example, if 1 mole (180 grams) of glucose is oxidized, forming CO2 and water, 686,000 calories of energy are liberated. We can imagine many different ways of splitting the glucose to arrive at the same products, but in each case the same energy would be released. The cell must take the glucose apart in small controlled steps and capture most of this energy in the form of ATP before it is contains a number of specific enzymes that speed the reaction along a specific path (i.e., by their presence, they single out the pat of “least resistance.”

Energy release from glucose or from glycogen (the storage form of glucose) always begins with a sequence of reactions called glycolysis that converts glucose into pyruvate with the concomitant production of ATP. Beginning with 6-carbon glucose, the reaction sequence is primed by investing 2 molecules of ATP to phosphorylate the molecule before it is broken into two 3-carbon fragments. These are processed further to yield 4 new ATP, a net profit of 2 (4-2(priming ATP)= 2). The entire sequence involves 10 reactions, each catalyzed by a specific enzyme, ending in the production of 2 molecules of pyruvate (a 3-carbon structure).

The presence of O2 is not required for any of these steps, and, although only a small fraction (about 2%) of the available energy in the original glucose has been trapped as ATP, the cell apparently can generate ATP anaerobically (in the absence of air or free oxygen). However, this glycolytic process of breaking down glucose works only if H atoms are stripped off the carbon skeletons and transferred to other molecules called NAD+.

2H (from carbohydrate)+NAD+—-NADH + H+

For every glucose, 4 H are transferreed to 2NAD+. But the total amount of NAD+ is very small (it is built from the vitamin niacin), and the reaction will stop iif we run out of NAD+. NADH needs to dump its H somewhere so it can reutrn for more. Normally, O2 serves as the final resting place for H, and H2O forms. In the absence of O2, pyruvate itself serves as a dumping ground for H, and lactic acid forms. NAD+ circulates, carrying H from high up in the glycolytic scheme to pyruvate and back.

When O2 is present, glycolysis proceeds as before, but now the role of NAD+ (and smaller H carrier, FAD) becomes more apparent. They have succeeded in trapping a good portion of the energy in the original glucose, and the presence of O2 allows this energy to be utilized to form ATP. Now, instead of using pyruvate, the H carriers transfer their H and energy to the respiratory chain, a system of carriers that reside within the mitochondrial membranes. In turn, the energized membranes of the mitochondria are able to produce 3 ATP for each NADH passed (only 2 ATP if the H donor is FAD).

Moveover, the availability of the respiratory chain allows energy contained in pyruvate to be tapped. Instead of absorbing H and forming lactate, pyruvate splits off a CO2 and the remaining 2-C (acetate) portion is transferred via acetyl-CoA to the Krebs cycle, where it is further degraded into 2 molecules of CO2. Again H are stripped off the carbon skeletonsby the H carriers, which deliver them to the respiratory chain and return for more. The final bookkeeping record for cellular combustion of 1 molecule of glucose is


                                                                  2 ATP + 2 NADH + 0 FADH2

2 pyruvate ——– acety- CoA                       0 ATP+ 2 NADH + 0 FADH2

2 turns of Kreb’s Cycle                                  2 ATP + 6 NADH + 2 FADH2

                                                   Total:       4 ATP + 10 NADH + 2 FADH2

Total ATP (after cashing H carriers in at resp. chain) 4 + (10×3) + (2×2) = 38 ATP

Daryl Conant, M.Ed.