Biochemistry in Perspective 101: Biochemistry of Metabolism in Health and Disease

Foreword

Biological organisms, such as humans and their individual cells, are incredibly complex and diverse. Nevertheless, certain unifying characteristics exist in all living things, from the simplest bacterium to the human being. They all use the same types of biomolecules and they all use energy. These molecules are known as proteins, lipids, glycans, and nucleic acids. From the construction, modification, and interaction of these components, our cells develop and carry out specific functions. Biochemistry draws on a wide range of scientific disciplines to explore and study these molecules, cells, and functions. This has sequentially allowed us to gain a better understanding of the human body at the molecular level, which has led to more effective treatments and cures in medicine. We will explore biochemistry in the context of this series, which examines the role it has played and will continue to play in our daily lives ranging from health, disease, nature, and research. In a nutshell, all life is the embodiment of biochemistry, and everything a living organism does is an expression of a biochemical process.

This 101 series is divided into six articles, including:

1. Biochemistry in Perspective 101: Amplifying Biochemistry Concepts

2. Biochemistry in Perspective 101: Biochemistry of Metabolism in Health and Disease

3. Biochemistry in Perspective 101: Applications of Biochemistry in Daily Life

4. Biochemistry in Perspective 101: Natural Biochemical Cycles

5. Biochemistry in Perspective 101: Biochemistry and its Applications in Drug Development

6. Biochemistry in Perspective 101: Advances and Prospects in Biochemical Research

Biochemistry in Perspective 101: Biochemistry of Metabolism in Health and Disease

In organisms, metabolism refers to the set of chemical reactions necessary for living. Metabolic functions include converting food energy into cellular energy, converting food into building blocks for proteins, lipids, nucleic acids, and some carbohydrates, and eliminating metabolic waste. Organisms rely on metabolic processes for growth, reproduction, and structure maintenance. All chemical reactions in living organisms require energy, from digestion to transportation (Campbell et al., 2016) [Figure 1]. In summary, metabolism is the sum total of chemical reactions taking place in the cells of living organisms.

Figure 1: Energy and human life (Wikimedia, n.d.).

Within metabolism, we have metabolic pathways. A metabolic pathway can be defined as a series of chemical reactions, catalyzed by enzymes, linked together that occur within the cell. The starting substrates, products, and intermediates of these reactions are known as metabolites. Metabolic pathways can either make biomolecules and utilize energy (anabolism) or break down biomolecules and release energy (catabolism). The figure below indicates various biomolecules and their conversion (Figure 2). Herein we will discuss various metabolic pathways and their relation to our health.

Figure 2: Metabolic basis for living (Geeks for geeks, n.d.).

Carbohydrate Metabolism

In addition to proteins and fats, carbohydrates make up one of the three main nutrients in foods and beverages. Your body breaks down carbohydrates into glucose. Glucose, or blood sugar, is the main source of energy for your body's cells, tissues, and organs. Carbohydrates are central to many essential metabolic pathways and are one of the most widely discussed topics among scientists across the world. In simple terms, carbohydrates are referred to as disaccharides, monosaccharides, and polysaccharides (Judge & Dodd, 2020).

A person's digestive system breaks down foods containing carbohydrates into digestible sugars, which enter the bloodstream. An increase in blood sugar levels prompts the pancreas to produce insulin, a hormone that helps cells absorb blood sugar. As cells absorb blood sugar, levels in the bloodstream begin to fall. As a result, the pancreas produces glucagon, a hormone that signals the liver to release stored sugar. As a result of this interplay between insulin and glucagon, the body maintains a steady supply of blood sugar in its cells, including those in the brain (Romano & Conway, 1996).

Type 2 diabetes occurs when the body cannot produce enough or use insulin properly. Carbohydrate metabolism plays a role in the development of type 2 diabetes. The onset of type 2 diabetes usually occurs over a number of years, beginning when muscle and other cells fail to respond to insulin. As a result of insulin resistance, blood sugar and insulin levels remain elevated for a long period of time after eating. As a result of the heavy demands placed on insulin-making cells, these cells eventually wear out and stop producing insulin (Saini, 2010; Taylor, 2012).

Glycolysis Pathway

Glycolysis is an example of a catabolic pathway, wherein a more complex glucose molecule is broken down to form energy (Campbell et al., 2016). The glycolysis pathway produces energy in the form of ATP, which is the first metabolic pathway of cellular respiration. It produces two molecules of pyruvate, ATP, NADH, and water (Figure 3). Glycolysis is a sequence of ten reactions catalyzed by different enzymes to eventually make pyruvate eventually. The vast majority of cells in the human body use glucose as fuel, and it is the only fuel red blood cells can use. Depending on the conditions, glycolysis may occur aerobically, in the presence of oxygen, or anaerobically (in the absence of oxygen, in the absence of oxygen pyruvate is transformed into lactic acid) (Nelson et al., 2008).

Figure 3: Glycolysis, Glucose is broken down into two pyruvate molecules, and in the process, two ATP molecules and one NADH molecule are created (Coursehero, n.d.).

Gluconeogenesis Pathway

The process by which glucose is made from non-carbohydrate carbon substrates is called gluconeogenesis (GNG), an anabolic pathway. It provides glucose during periods of insufficient or absent dietary intake. Gluconeogenesis is essentially the reversal of glycolysis. It is largely carried out in the liver and kidney cortex (the outside layer of the kidney). Humans and many other animals use it along with glycogenolysis (the breakdown of glycogen) to maintain blood sugar levels, avoiding low levels (hypoglycemia). During gluconeogenesis glucose is stored in the liver.

Glycogenesis Pathway

When glycogen is produced (glycogenesis), glucose molecules are added to glycogen chains for storage. In the absence of readily available glucose, the body creates glycogen through glycogenesis to store these molecules (Figure 4). Glycogen is not the same as fat, which is stored for long-term energy. It is common for people to rely on glycogen stores between meals when their blood glucose concentration is low. As a result, the body turns to its glycogen stores, undergoing the reverse process of glycogenesis. Glycogenolysis is the process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose.

Figure 4: Glycogenesis pathway (Sciencefacts, n.d.).

Insulin and Low-carb Diets

High carbohydrate diets became very popular in the 1970s, both among athletes and the general public. It was believed that a diet containing 60–70% carbohydrates and 15–20% fat and protein would be the healthiest (because of the high carbohydrate-to-fat and protein ratio) and would also be the best for athletes (because of the high levels of carbohydrates for replenishing glycogen). In the 1990s however, diets based on lower carbohydrate levels became popular. These diets recommended a lower carbohydrate ratio to protein and fat (50/25/25 ratio of carbohydrate/protein/fat). One of the most notable diets was the Zone Diet (Figure 5), created by Dr. Barry Sears. His book, The Zone: A Dietary Road Map (Sears, 1996), went on to become a No. 1 New York Times best-seller and sold over two million copies in the United States. As a result of the diet, weight loss was promoted through the reduction of calories consumed as well as the prevention of insulin spikes, which contributes to maintaining insulin sensitivity (Devinsky, 2022). Because of the myriad health problems attributed to too much dietary fat, people maintained higher carbohydrate diets in the belief that carbohydrates were healthier than fats.

However, too many carbohydrates can also be negative. For one thing, excess carbohydrates become fat. In contrast to endurance athletes, nonathletes do not need to replenish muscle and liver glycogen as frequently as athletes. The production of insulin is also stimulated by a high-carbohydrate meal. Insulin plays several essential roles. It triggers fat storage in the body, additionally, it regulates blood sugar levels and helps break down fats and protein. A high-carbohydrate meal can also lead to reactive hypoglycemia, which usually occurs a few hours after eating a meal (Brun et al., 2000). A person experiences this when they have too much insulin in their blood at the wrong time, and experience a “blood sugar crash”, making people feel weak or shaky. The Zone Diet was designed to avoid reactive hypoglycemia and the effects insulin has on fat storage. Diet however is a very personal thing and countless people have found that a reduced carbohydrate diet has made them feel better and actually helped them to lose weight. Others find just the opposite.

Figure 5: The zone diet by Dr Sears (Supplements diets, 2020).

Sports and Metabolism

Athletes especially those training at the elite level are more aware of the results of aerobic and anaerobic metabolism than nonathletes. In addition to genetic endowment and training, athletes must also have a thorough understanding of their physiology and metabolism. Serious athletes must understand the nature of metabolism as it relates to their chosen sport in order to plan a proper diet that will result in maximum performance. A working muscle has four different sources of energy available after a period of rest. Initially, all four energy sources are available to the muscle. When the creatine phosphate runs out, only the other sources are left. Next up is the muscle glycogen. When it runs out, the anaerobic boost it provided slows down, and when the liver glycogen is gone, only aerobic metabolism to carbon dioxide and water is left (Lemon, 1995).

While it is hard to determine the exact amount each of these nutrients might supply a rapidly working muscle, simple calculations indicate that there is less than a one-minute supply of creatine phosphate, a figure that is comparable with the duration of sprints, which typically last less than one minute. Athletes can purchase creatine supplements in health food stores, and results suggest these supplements are effective for powerlifting and short sprints, such as the 100-meter dash. The muscles contain about 10-30 minutes' worth of glycogen, but the amount varies dramatically based on the intensity of the sport/exercise. The level of muscle glycogen at the start of a long-distance running event can significantly influence an athlete's performance. This figure could be significantly affected by glycogen loading (MacLaren & Morton, 2011).

Athletes who are well-conditioned and trained actually have more mitochondria in their muscle cells, which helps with aerobic metabolism (MacLaren & Morton, 2011). Aerobic metabolism plays a role in long-distance events, such as marathons and road cycling. “Fat burning” is the term frequently used, and it reflects metabolic fat. In marathoners and cyclists, with minimal body fat, fatty acids are degraded into smaller substances, which enter another metabolic cycle. A marathon, which can take between two and three hours for very fit runners, makes more use of fatty acids and requires less oxygen than a seven-hour road cycling race. Clearly, there are differences in metabolism for sports even within the category known as endurance events.

Perhaps the most studied athlete of modern times is cyclist Lance Armstrong. In 1993, he was the world professional road race champion and had already won a few stages of the prestigious cycling race, the Tour de France. The powerfully built rider excelled in time trials and single-day road races, but he wasn't considered a threat in the major stage races due to his inability to climb major European mountains. After suffering a disappointing Olympic Games in Atlanta in 1996, he was diagnosed with testicular cancer, which had spread to several organs, including his brain. He was given little chance to live, but after several surgeries and intense chemotherapy, he recovered and resumed his cycling career.

Figure 6: Lance Armstrong at the Tour de France wearing the yellow jersey (Daily mail, n.d.).

As a result of his hospitalization and chemotherapy, he lost 15 to 20 pounds, increased his muscular efficiency and output power, and in 1998, he was not only competitive but also a true contender in the World Championships. In the next few years, he would become the first cyclist to win seven Tour de France titles, surprising cycling fans by how well he climbed the Pyrenees. No one had ever won six races before Lance Armstrong.

He was also the second American to win this event. He always was an amazing aerobic machine, and when his metabolism did not have to carry as much weight up the mountains, he was able to climb with the best in the world. Although, it was his will to win that gave him his true strength, which he attributes to his ordeal with cancer and upbringing.

Conclusion

To conclude, metabolism plays a crucial role in maintaining overall health. Our bodies use it to convert food into energy, building blocks for cells, and essential molecules. An efficient metabolism ensures optimal nutrient utilization, hormone regulation, and cellular health. In contrast, an impaired metabolism can lead to obesity, diabetes, cardiovascular disease, and metabolic syndrome. The key to maintaining a healthy metabolism is a balanced and nutritious diet, regular physical activity, and adequate sleep. In order for the body to function properly, it must consume nutrient-dense foods, such as fruits, vegetables, whole grains, lean proteins, and healthy fats. By exercising, you not only burn calories, but also improve insulin sensitivity, stimulate metabolism, and promote muscle growth. To maintain a healthy metabolism, hormone production, and overall energy balance, adequate sleep is essential.

It is important to note that individual variations exist in metabolism due to factors such as genetics, age, gender, and body composition. It is possible to optimize metabolic function through a healthy lifestyle, regardless of whether someone has a naturally faster or slower metabolism. In order to support our overall health, we must understand how metabolism and health are interconnected. Maintaining a healthy weight, maintaining a healthy energy level, reducing the risk of chronic diseases, and improving our quality of life can all be enhanced by adopting healthy habits and promoting a balanced metabolism. We must commit to nurturing our bodies and ensuring their health for the long term by prioritizing a healthy metabolism.

Bibliographical References

Brun, J. F., Fédou, C., & Mercier, J. (2000). Postprandial reactive hypoglycemia. Diabetes and metabolism, 26(5), 337–352.

Campbell, M. K., Farrell, S. O., & McDougal, O. M. (2016). Biochemistry. Cengage Learning, 550–554.

Devinsky, O. (2022). The refined carbohydrate-insulin model of obesity. The American Journal of Clinical Nutrition, 115(2), 592–593.

Judge, A., & Dodd, M. S. (2020). Metabolism. Essays in Biochemistry, 64, 607–647. https://doi.org/10.1042/EBC20190041

Lemon, P. W. (1995). Do athletes need more dietary protein and amino acids? International Journal of Sport Nutrition and Exercise Metabolism, 5(s1), S39–S61.

MacLaren, D., & Morton, J. (2011). Biochemistry for sport and exercise metabolism. John Wiley & Sons, 145.

Nelson, D. L., Lehninger, A. L., & Cox, M. M. (2008). Lehninger principles of biochemistry. Macmillan.

Romano, A., & Conway, T. (1996). Evolution of carbohydrate metabolic pathways. Research in microbiology, 147(6-7), 448–455.

Saini, V. (2010). Molecular mechanisms of insulin resistance in type 2 diabetes mellitus. World journal of diabetes, 1(3), 68.

Sears, B., & Lawren, B. (1996). The Zone: A dietary road map. (No Title).

Taylor, R. (2012). Insulin resistance and type 2 diabetes. Diabetes, 61(4), 778.

Visual Sources

Cover image: Retrieved July 14, 2023, from https://www.canva.com/photos/MADq30cP5Ho-f023-0936/

Figure 1: Wikimedia. (n.d.). Retrieved July 13, 2023, from https://commons.wikimedia.org/wiki/File:Energy_and_life.png

Figure 2: Geeks for geeks. (n.d.). Retrieved July 13, 2023, from https://www.geeksforgeeks.org/metabolism-living-state-basis/

Figure 3: Coursehero. (n.d.). Retrieved July 13, 2023, from https://www.coursehero.com/sg/cell-biology/glycolysis/

Figure 4: Sciencefacts. (n.d.). Retrieved July 14, 2023, from https://www.sciencefacts.net/glycogenesis.html

Figure 5: Supplements diets. (2020). Retrieved July 14, 2023, from http://54.70.2.84/zone-diet/

Figure 6: Daily mail. (n.d.). Retrieved July 14, 2023, from https://www.dailymail.co.uk/news/article-2268851/Armstrong-help-clean-cycling---wont-talk-U-S-doping-agency.html