Metabolic Misconceptions: Part 6: by Fred Dimenna, CSCS

ATP is the transfer mechanism that allows us to use the energy contained in the foods we eat to drive energy-requiring processes in the body. Once it is hydrolyzed (broken down to transfer energy), ATP can be reformed in a number of ways. Other than when demand is very high or increased suddenly, aerobic ATP rebuilding predominates. Consequently, this process is in effect 85 percent of the time. The two primary fuels used to reform ATP aerobically are carbohydrates and fat, although protein can be used in a pinch, as well.

If fat has accumulated on your body, there is one thing you can state for sure. On a net basis, you have ingested more energy throughout your years than the amount you required, and the excess was stored as adipose tissue. But, in reality, those dreaded adipose deposits are not that bad if you consider other fuel storage options. They provide for very efficient accommodation because of their low water content and actually contain 3,500 calories of ATP-producing substrate per pound! If you’re not starving on a desert island, however, it’s hard to appreciate this benefit.

Fat is very efficient to store, but not nearly as economical to use. In fact, once it’s packed away, accessing the energy contained in adipose tissue is like unearthing a buried treasure. The reward is substantial, but you’ve got your work cut out for you before you can reap it. Accessing fat stores begins with the dispatch of messengers, which signal the need to increase the fuel that is circulating in the blood. Specifically, the sympathetic branch of the autonomic nervous system sends out its activators (epinephrine and norepinephrine), which bind to beta receptors on fat cell membranes. This binding activates an enzyme (adenylate cyclase), which causes the formation of a secondary messenger (cyclic AMP) within the cell.

Cyclic AMP keeps the ball rolling by stimulating a regulatory protein consisting of two sub-units. The catalytic sub-unit activates the inactive form of Hormone-Sensitive Lipase (HSL) by phosphorylating (adding a phosphate group to) it. This phosphate comes at the expense of a molecule of ATP, so this is an energy-requiring (endergonic) reaction. The activation of HSL is the rate-limiting step during this chain of events. Once its active form is present, HSL divides triglyceride (the storage form of fat) into its fatty acid components. This necessitates three hydrolysis (water-requiring) reactions. The end result is cleaved fatty acids, which can either be converted to fatty acyl CoA to reform triglyceride (all that work for nothing!) or released from the fat cell into circulation. If released into the blood stream, fatty acids must be attached to a protein (albumin) in order to circulate. Once this merger occurs, the circulating fats are called free fatty acids because they are free to move to where energy is required. When they find a cell where demand exists, another series of reactions begins. Once free fatty acids enter the cytoplasm of an "ATP-hungry" cell, they are attached to a fatty acid binding protein. But before they can enter the cell’s mitochondrion (the specific sub-division where aerobic ATP building occurs), they must be primed, another energy-requiring step. This results in the formation of fatty acyl CoA, but also creates a problem. The inner mitochondrial membrane is impermeable to CoA, so a transport mechanism (a protein carrier known as carnitine/acyl carnitine translocase) must be used to shuttle the fatty acids in.

Once fatty acyl CoA is within the mitochondrial matrix, the long-chain fatty acids must be divided into usable two-carbon sub-units one segment at a time. This process is called beta oxidation. Each breakdown cycle consists of four reactions and yields one two-carbon unit, which is known as acetyl CoA. A typical 18-carbon saturated fatty acid, therefore, yields nine acetyl Co A, which can then be oxidized to phosphorylate ADP (the product of ATP hydrolysis) into ATP to satisfy demand. Unsaturated fatty acids require an additional step during this cycle.

Acetyl CoA oxidation requires that these molecules undergo a cyclical series of reactions known as the Krebs Cycle. The primary objective of this sequence is to generate electrons that will be transferred to oxygen to form water. The free energy release generated by the movement of these electrons is harnessed to rebuild ATP, much like the movement of water turns a water wheel to power a dynamo.

As dense sources of fuel, fatty acids that undergo beta oxidation generate a considerable ATP payoff. A typical saturated fatty acid like palmitic acid (which contains 16 carbons), for example, provides a net yield of 130 ATP per molecule! But with this fruitful harvest comes an associated cost. The actual energy produced is low in relation to the oxygen that will have to be consumed to dispose of the electrons once their potential energy has been tapped. Because of the many steps required along the way, fat use cannot keep pace and must take a backseat to more accessible fuel options.

Fred DiMenna, a Certified Strength and Conditioning Specialist and Lifestyle and Weight Management Consultant is a two-time Natural Mr. United States and a WNBF drug-free professional bodybuilder. Visit him at or email: