Since all digestible forms of carbohydrates are eventually transformed into glucose, it is important to consider how glucose is able to provide energy in the form of adenosine triphosphate (ATP) to various cells and tissues. Glucose is metabolized in three stages:
The breakdown of glucose to provide energy begins with glycolysis. To begin with, glucose enters the cytosol of the cell, or the fluid inside the cell not including cellular organelles. Next, glucose is converted into two, three-carbon molecules of pyruvate through a series of ten different reactions. A specific enzyme catalyzes each reaction along the way and a total of two ATP are generated per glucose molecule. Since ADP is converted to ATP during the breakdown of the substrate glucose, the process is known as substrate-level phosphorylation. During the sixth reaction, glyceraldehyde 3-phosphate is oxidized to 1,3 bisphosphoglycerate while reducing nicotinamide adenosine dinucleotide (NAD) to NADH, the reduced form of the compound. NADH is then shuttled to the mitochondria of the cell where it is used in the electron transport chain to generate ATP via oxidative phosphorylation, which will be described later.
The most important enzyme in glycolysis is called phosphofructokinase (PFK)and catalyzes the third reaction in the sequence. Since this reaction is so favorable under physiologic conditions, it is known as the "committed step" in glycolysis. In other words, glucose will be completely degraded to pyruvate after this reaction has taken place. With this in mind, PFK seems as if it would be an excellent site of control for glucose metabolism. In fact, this is exactly the case. When ATP or energy is plentiful in the cell, PFK is inhibited and the breakdown of glucose for energy slows down. Therefore, PFK can regulate the degradation of glucose to match the energy needs of the cell. This type of regulation is a recurring theme in biochemistry.
There are many compounds that are formed and recycled during the Krebs Cycle (Citirc Acid Cycle). These include oxidized forms of nictotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) and their reduced counterparts: NADH and FADH2. NAD+ and FAD are electron acceptors and become reduced while the substrates in the Krebs Cycle become oxidized and surrender their electrons.
The Krebs Cycle begins when the pyruvate formed in the cytoplasm of the cell during glycolysis is transferred to the mitochondria, where most of the energy inherent in glucose is extracted. In the mitochondria, pyruvate is converted to acetyl CoA by the enzyme pyruvate carboxlase. In general, Acetyl-CoA condenses with a four carbon compound called oxaloacetate to form a six carbon acid. This six-carbon compound is degraded to a five and four carbon compound, releasing two molecules of carbon dioxide. At the same time, two molecules of NADH are formed. Finally, the C-4 carbon skeleton undergoes three additional reactions in which guanosine triphosphate (GTP), FADH2 and NADH are formed, thereby regenerating oxaloacetate. FADH2 and NADH are passed on to the electron transport chain (see below) that is embedded in the inner mitochondria membrane. GTP is a high-energy compound that is used to regenerate ATP from ADP. Therefore, the main purpose of the Krebs Cycle is to provide high-energy electrons in the form of FADH2 and NADH to be passed onward to the electron transport chain.
The high-energy electrons contained in NADH and FADH2 are passed on to a series of enzyme complexes in the mitochondrial membrane.
Despite oxidative phosphorylation's large capacity for energy production, the rate of electron transport and therefore ATP generation is limited by oxygen, the final electron acceptor/oxidizing agent in the chain. Oxygen is readily available to the cell through circulating hemoglobin but can only be used when the energy requirements of the cell do not exceed the rate of ATP production via oxidative phosphorylation. This is often the case because the rate at which electrons can be transferred to oxygen is relatively slow. In its search for a more readily available energy production pathway, the body will switch to anaerobic glycolysis as its primary provider. Despite requiring tendifferent reactions to form its end product pyruvate, glycolysis occurs quite rapidly. During these ten reactions, two net ATP are formed per molecule of glucose, which help working muscles satisfy energy requirements quickly. However, upon inspection of the Krebs Cycle figure above, it is clear that ATP generation through this process would stop abruptly if NAD+ were not regenerated to act as an electron acceptor in the conversion of glyceraldehyde 3-phosphate to 1,3 biphosphoglycerate. The body has adapted to this requirement by using pyruvate to oxidize (remove electrons) from NADH, thereby forming NAD+ and lactic acid in an oxidation-reduction reaction. An enzyme known as lactate dehydrogenase carries out this conversion, allowing NAD+ to be recycled quickly for repeated use in glycolysis.
Like most things that seem too good to be true, there is a problem with anaerobic glycolysis. The production of lactic acid during this process can decrease the pH of active local tissue enough to cause cramping and fatigue. At moderate exercise intensities, the body does have a limiting mechanism to cope with this entirely new problem. While working muscle releases lactic acid into the bloodstream during anaerobic exercise, the liver is busy absorbing and converting lactic acid back to pyruvate by the same enzyme found in anaerobic glycolysis. Pyruvate is then recycled into circulation to feed working tissue. In this way, part of the metabolic burden is shifted to the liver. If oxygen is available and aerobic conditions persist, pyruvate can enters the mitochondria to be used in the Krebs cycle and electron transport chain if oxygen is available. This relatively simple process is known as the Cori cycle.
During aerobic conditions, the level of lactic acid can be maintained at a low level in the blood for a significant period of time through the Cori cycle. The greater the fitness level of an individual, the longer the lactic acid level can be maintained. However, even the best of active athletes reach a point where their bodies begin to produce more lactic acid than their liver can metabolize and it begins to accumulate in the blood. This point is known as the lactic acid threshold for that individual and is dependent mostly on cardiac performance if aerobic conditions persist.
The metabolism of carbohydrates can also be considered in the context of exercise strategies. For example, what kinds of foods should be eaten before a particular type of exercise? For almost any activity, most dieticians suggest a diet high in starch and other complex carbohydrates. Since this is also recommended for most diets in general, eating a diet high in carbohydrates should not be difficult. Furthermore, dieticians also recommend that people avoid meals high in fats and proteins before exercise, since these foods inhibit gastric emptying and require longer to digest than other foods. Since the sympathetic nervous system inhibits the gastrointestinal tract during exercise, any remaining quantities of food in the stomach may lead to cramping and acid reflux into the esophagus. Lastly, simple sugars that are readily absorbed by the intestine should be avoided because they cause rapid fluctuations in blood glucose, thereby affecting the circulating energy supply. Unlike simple sugars, starch must be broken down into glucose before being absorbed into the blood. In this way, the energy supplied by starchy foods such as pasta and vegetables can be absorbed more slowly and be available for longer than other simple sugars.
How long before the onset of exercise should a meal be consumed? For most people, a meal high in carbohydrates will be emptied from the stomach after three hours of fasting. As mentioned earlier, exercising on an empty stomach is physiologically beneficial and eating three hours before an exercise bout will usually give the stomach plenty of time to empty. Although the circulating glucose provided by starchy foods is used as energy for working muscle to some extent, most of the energy used comes from glycogen stores in the muscle itself. Therefore, it is important to be eating high carbohydrate meals days before an event or exercise bout in order to build up glycogen stores in the muscle and liver. Because of glycogen's branched structure and hydrophilic hydroxyl groups, it is able to absorb significant quantities of water, which helps keep the body hydrated during exercise.
Losing weight can also be related to carbohydrates. Fluctuations in hormones caused by the ingestion of carbohydrates make the burning or utilization of fats more difficult. For example, eating a meal high in carbohydrates will cause the release of insulin, a hormone that allows cells to uptake glucose. However, insulin also acts on adipose tissue to inhibit the release of fatty acids and promote their synthesis. Since most people are trying to become leaner by burning fat through exercise, eating a meal before exercise may not be the best idea for losing weight. The best time of the day to exercise with the intention of losing weight is in the morning. Since no food has been consumed since the last meal of the previous day, levels of insulin in the blood will be low. Furthermore, levels of glucagon will increase due to fasting and this hormone stimulates the release of fatty acids from adipose tissue while inhibiting the breakdown of glycogen from the liver. Epinephrine and Norepinephrine are also secreted in response to exercise and these hormones mimic the effects of insulin by increasing availability of fatty acids in the blood. Of course, fatty acids may only be utilized by working muscle under aerobic conditions. Therefore, in order to burn fats effectively, the ratio of insulin to glucagons must be low and the body must be performing exercise at a relatively low intensity for a prolonged period of time.
It is true that some of the glucose ingested can be converted to fatty acids by the liver when there is an excess of energy available to the body. But eating a diet low in carbohydrates is not a good solution to a weight problem either. For example, many weight loss programs suggest diets that are high in protein and low in carbohydrates. Besides high levels of ammonia in the body through the breakdown of protein, a low carbohydrate diet will force the body into a condition known as ketosis. Ketosis comes from the root word ketones which are produced in the liver through the incomplete breakdown of fat. Although some of the amino acids that come from the diet are gluconeogenic, meaning glucose producing, many amino acids are ketogenic and cannot enter the citric acid cycle. Therefore, the level of ketones in the body rises while levels of glucose fall and many organs begin to function less efficiently, including the brain, which relies heavily on glucose. Furthermore, fats can only be metabolized when there is a certain amount of glucose present to produce oxaloacetate that condenses with acetyl CoA in the citric acid cycle. Since fatty acids are degraded directly to acetyl CoA, they cannot be used as an energy source. Instead, they too are transformed in ketones. Although many tissues can utilize ketones for energy, high levels in the blood stream are dangerous and low amounts of glucose in the blood can be detrimental to the brain.
In addition, low carbohydrate diets without exercise will slow down metabolism. Weight loss may be realized but the type of weight that is actually lost may include muscle mass as well as fat. With less lean body mass, resting metabolic rates will decrease since skeletal muscle requires more energy at rest and during exercise than adipose tissue. In conclusion, exercising during fasting periods and eating a diet high in carbohydrates will not only increase well being, but will also help to lose weight more effectively. Monitoring the amount of carbohydrate intake with the amount of exercise will help to refine weight loss.