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Biochemistry in Perspective 101: Amplifying Biochemistry Concepts

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 decided 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: Amplifying Biochemistry Concepts


History of Biochemistry

Historically, biochemistry can be traced back to the ancient Greeks, who were interested in life's composition and processes; however, biochemistry as a specific science only emerged around the turn of the 19th century. The discovery of the first enzyme, diastase (today's amylase), by Anselme Payen in 1833 may have been the beginning of biochemistry. An enzyme can be defined as a substance produced by a living organism, acting as a catalyst, effectively facilitating and bringing about specific biochemical reactions. While many others consider the demonstration of alcoholic fermentation in cell-free extracts in 1897 by Eduard Buchner as the birth of biochemistry (Singh et al., 2004).


The term biochemistry, which means life and chemistry and the combination of biology and chemistry, was first recognized in 1848. In 1877, German scientist Felix Hoppe-Seyler, who edited the first biochemical journal—The Journal for Physiological Chemistry—used the term in the abstract of the journal (Singh et al., 2004). The research was focused on the chemical analysis of biological tissues and fluids. However, several sources have recognized German chemist Carl Neuberg as the founder of the term, who first described it in 1903 as a scientific discipline of its own. Nevertheless, scientists became intrigued by biological molecules and their dynamic nature.


Eduard Buchner's alcoholic fermentation demonstration set the stage for this project (Figure 1). Fermentation is the conversion of glucose to ethanol, alcohol like the kind we consume, and carbon dioxide, a gas that presents as foam and bubbles. Fermentation is carried out by microorganisms; for example, yeast is used in the brewing of beer as well as winemaking, and as a result, fermentation was thought to be the result of living organisms. Buchner’s work established that chemical changes in living cells occurred through the action of enzymes and that these processes could be dissected and understood by isolating and characterizing enzymes (Kohler, 1971). The isolation and physicochemical characterization of enzymes led to a new phase in biochemical research. Research on this topic continues today with the aid of recombinant DNA technology and molecular biology techniques.

Figure 1: Eduard Buchner (Wikimedia, n.d.).
How Biochemistry Describes Life Processes

Humans, as well as their individual cells, are extremely complex and diverse. From the simplest bacterium to the most sophisticated human being, certain unifying characteristics are present in all living things. As a result, organisms can be studied with the methods of chemistry and physics. The answers to important biochemical questions can be found in disciplines that seem unrelated to biochemistry. The field itself draws on many disciplines, and its multidisciplinary nature allows the use of many different scientific approaches to answer questions about the molecular nature of life processes.

The activities within a cell are similar to the transportation system of a city. In a cell, cars, buses, and taxis represent molecules involved in reactions. The routes travelled by vehicles can be compared to the reactions that occur during the life cycle of a cell. The most prominent difference is that many vehicles can travel more than one route. For instance, a car or taxi can go almost anywhere, whereas other, more specialized modes of transportation, such as subways and trains, are restricted to a single route. Similarly, some molecules play multiple roles, while others participate only in specific reactions. We will also see that many reactions within a cell operate simultaneously, whereas the routes of a city's transportation system also run simultaneously (Campbell et al., 2016).

In further observation of this comparison a larger city has a more diverse transportation system than a smaller city. A large city may have all of these plus other transportation, including streetcars or subways, unlike a small city which may only have cars, buses, and taxis. Similarly, some reactions occur in all cells, while others occur in only certain types of cells. The larger, more complex cells of larger organisms possess more structural features than the simpler cells of smaller organisms such as bacteria (Campbell et al., 2016).


The Origin of Biomolecules

Biological macromolecules are large molecules necessary for life that are built from smaller organic molecules. There are four major classes of biological macromolecules (carbohydrates, lipids, proteins, and nucleic acids); each is an important cell component and performs a wide array of functions. Large macromolecules are built up from small molecules such as amino acids, vitamins, fatty acids, neurotransmitters, and hormones.

In experiments, simple compounds (chemical substances made up of two or more elements bonded together) from the early atmosphere have been allowed to react under the varied conditions that might have existed in their early days. This experiment indicates that simple compounds are capable of reacting abiotically (without the presence of life) to produce biologically important compounds, such as the components of nucleic acids and proteins.


Of historical interest is the well-known Miller-Urey experiment, shown schematically in Figure 2. An electric discharge, simulating lightning, is passed through a closed system that contains hydrogen, methane, ammonia, and water. In the experiment, Miller used a small flask of water, which was heated to induce evaporation, and a larger flask was used to collect the water vapor, as represented in Figure 2. A continuous electrical spark was discharged between a pair of electrodes inside the larger flask. The spark passed through the mixture of gases and water vapor stimulating lightning, which was hypothesised to be present in the primordial atmosphere of the earth. Following the experiment, the apparatus just below the larger flask was cooled, and the condensed water was collected into a U-shaped trap at the bottom of the apparatus. After a day, the solution that was collected at the trap turned pink, and after a week of continuous operation, the solution turned a deep red and turbid. The boiling flask was then removed, and mercuric chloride was added to prevent microbial contamination. Furthermore, the chemical reaction was stopped by adding barium hydroxide and sulfuric acid and was then evaporated to remove any impurities. Analysis of the mixture was achieved using paper chromatography, and Miller identified five amino acids present in the solution: glycine, alpha-alanine and beta-alanine, while aspartic acid and alpha-aminobutyric acid (AABA) were less certain due to the spots being faint (Miller, 1953).

Figure 2: Miller-Urey experiment (Shutterstock, n.d.).
Basic Principles of Biochemistry

The Nature of Metabolism

Anabolism and catabolism are the two broad classes of biochemical reactions that make up metabolism. Anabolism is the process of making more complex molecules from simpler ones. These chemical reactions require energy, also known as an endergonic process. Catabolism is the breakdown of large molecules into smaller parts for use in cellular respiration. Catabolism drives anabolism. Anabolic processes are powered by the hydrolysis of adenosine triphosphate (ATP). Anabolism involves reduction and requires an energy input to occur. Examples of anabolic processes include bone mineralization and muscle growth (Bonora et al., 2012).


Catabolism refers to the breakdown of molecules into smaller units that can be used for energy production or oxidized to release energy. Examples of the large molecules that are broken down include polysaccharides, lipids, nucleic acids, and proteins. The smaller molecules that are formed from this process are molecules such as monosaccharides, fatty acids, nucleotides, and amino acids. In the formation of these wastes, chemical-free energy is released, some of which is lost as heat, but the rest is used for the synthesis of adenosine triphosphate (ATP) (Bonora et al., 2012). ATP helps and facilitates a way for the cell to transfer the energy released by catabolism to the energy-requiring reactions that make up anabolism. A schematic description of the differences between anabolism and catabolism can be seen in Figure 3. In addition to glycolysis and the citric acid cycle, catabolic processes include the breakdown of muscle proteins into amino acids that are used for gluconeogenesis, the breakdown of fat in adipose tissue into fatty acids, and the oxidative deamination of neurotransmitters by monoamine oxidase.

Figure 3: Anabolism versus catabolism (Judge et al., 2020).
Cell Communication

A cell's ability to receive, process, and transmit signals is called cell signalling or cell communication. Cell signalling is a fundamental property of all cellular life in eukaryotes and prokaryotes. A eukaryote is a cell or any organism that contains a distinct, clearly defined membrane-bound nucleus, whereas prokaryotes are devoid of any well-defined nucleus. All animals, plants, fungi and unicellular organisms are eukaryotes, prokaryotes are mainly bacteria and archaea. A signal originating outside the cell can be physical (e.g., mechanical pressure, voltage, temperature, light) or chemical (e.g., small molecules, peptides, or gas). A wide range of biosynthetic pathways can produce signalling molecules, which are released by passive or active transport mechanisms, as well as by cell damage (Lodish et al., 2007).

Chemical signals or physical stimuli can be detected by receptors, which are vital to cell signalling. Generally, receptors are proteins found on the surface of cells or within the cytoplasm, organelles, and nuclei of cells. Extracellular signals (or ligands) bind to cell surface receptors, causing a conformational change in the receptor that initiates enzymatic activity or opens or closes ion channels. It is possible for receptors to be linked to enzymes or transporters rather than to enzymatic or channel-like domains. The mechanism of other receptors, such as nuclear receptors, differs from that of others, such as the function of DNA binding and the localization of the receptor in the nucleus (Lodish et al., 2007).


Biological Molecules

An example of a macromolecule is a protein or nucleic acid, a very large molecule important to biochemical and physiological processes. Macromolecules are often considered polymers, which are composed of smaller repeating units called monomers. Biological macromolecules such as DNA, proteins, and carbohydrates are the most common polymers in biochemistry, while lipids, nanogels, and macrocycles are large non-polymeric molecules (Figure 4). DNA, RNA, and proteins are three essential biopolymers used by all living organisms, and each one plays an essential role in the cell. In a nutshell, DNA makes RNA, and RNA makes proteins.


All three types of genetic material are made up of repeating structures of related building blocks (nucleotides in the case of DNA and RNA, amino acids in the case of proteins. In general, they are all unbranched polymers and so can be represented in the form of a string. Indeed, they can be viewed as a string of beads, with each bead representing a single nucleotide or amino acid monomer linked together through covalent bonds into a very long chain (Bada et al., 2002).

Figure 4: Different biomolecules (Major differences, n.d.).
Enzymology

An enzyme is a protein that accelerates chemical reactions by acting as a biological catalyst. A substrate is a molecule which reacts with an enzyme, and the enzyme converts the substrate into a product. To sustain life, almost all metabolic processes in the cell require enzyme catalysis. The individual steps of metabolic pathways are catalyzed by enzymes and the study of enzymes is called enzymology.


Enzymes are known to catalyze more than 5,000 biochemical reaction types. It is the unique three-dimensional structure of enzymes that gives them their specificity. In general, enzymes are globular proteins that function alone or as part of larger complexes. It is the sequence of amino acids that determines the enzyme's structure and catalytic activity. Despite the fact that structure determines function, it is still difficult to predict new enzymatic activity based solely on structure. Heat or chemical denaturants destroy enzyme structures, causing them to unfold (denature). This disruption normally results in a loss of enzyme activity. As enzyme denaturation is usually a consequence of temperatures above a species' normal level, bacteria living in volcanic environments such as hot springs are prized for their ability to function at high temperatures, allowing enzyme-catalyzed reactions to operate at high rates (Campbell et al., 2016).


Conclusion

An understanding of the underlying processes and intricate workings of living organisms requires a thorough understanding of the various biochemical concepts. As a discipline, biochemistry encompasses a wide range of interconnected topics that contribute to the understanding of life at a molecular level. One crucial concept in biochemistry is the study of macromolecules, including proteins, lipids, nucleic acids and carbohydrates. These molecules play vital roles in cellular structure, function and regulation. A thorough understanding of their structure, synthesis and interactions gives us insight into how they contribute to a variety of biological processes. Enzymes are proteins that catalyse biochemical reactions in cells, enabling metabolic pathways to occur at a suitable rate. Exploring enzyme kinetics, mechanisms, and regulation helps us understand the fundamental principles governing cellular metabolism. A central concept in biochemistry is metabolism, which describes the chemical reactions that occur within living organisms. The process involves the conversion of nutrients into energy and the synthesis of biomolecules for growth, repair, and reproduction. Understanding metabolic pathways, such as glycolysis, the citric acid cycle, and oxidative phosphorylation, provides insights into energy production and utilization. By understanding the varying biochemical concepts, we become more equipped to understand life's underlying mechanisms. It contributes to the advancement of medicine, biotechnology, and our understanding of health and disease. The study of biochemistry will remain crucial in unravelling the complexity of living systems and advancing science as our knowledge expands.

Bibliographical References

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). How cells obtain energy from food. In Molecular Biology of the Cell. 4th edition. Garland Science.


Bada, J. L., & Lazcano, A. (2002). Some like it hot, but not the first biomolecules. Science, 296(5575), 1982–1983.


Bonora, M., Patergnani, S., Rimessi, A., De Marchi, E., Suski, J. M., Bononi, A., Giorgi, C., Marchi, S., Missiroli, S., & Poletti, F. (2012). ATP synthesis and storage. Purinergic signalling, 8, 343–357.


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


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


Kohler, R. (1971). The background to Eduard Buchner's discovery of cell-free fermentation. Journal of the History of Biology, 35–61.


Lodish, H., Berk, A., Kaiser, C., Krieger, M., Scott, M., Bretscher, A., & Ploegh, H. (2007). Cell signaling I: Signal transduction and short-term cellular processes. Molecular Cell Biology, 6th ed.; WH Freeman and Company: New York, NY, USA, 623–664.


Miller, S. (1953). Penghasilan Asid Amino di bawah Keadaan Bumi Primitif Kemungkinan. Sains, 15, 528–529.


Sapp, J. (2005). The prokaryote-eukaryote dichotomy: meanings and mythology. Microbiology and molecular biology reviews, 69(2), 292–305.


Singh, P., Batra, H., & Naithani, M. (2004). History of biochemistry. Bulletin of the Indian Institute of History of Medicine (Hyderabad), 34(1), 75–86.


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Nicole Galetti

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