Biochemistry
Biochemistry is the branch of science that studies the chemical substances and processes occurring in living organisms, integrating principles from biology and chemistry to understand life at the molecular level.[1] It examines the structure, properties, and interactions of key biomolecules, including proteins, nucleic acids (such as DNA and RNA), carbohydrates, and lipids, which form the foundation of cellular function and organization.[2] The field aims to explain biological phenomena through chemical mechanisms, revealing how these molecules enable processes like metabolism, signal transduction, and genetic information transfer.[3] The discipline of biochemistry emerged in the late 19th and early 20th centuries from chemical analyses of biological tissues, marking a shift from descriptive physiology to molecular explanations of life.[4] Pioneering work, such as Eduard Buchner's 1897 demonstration of cell-free fermentation, established enzymes as catalysts for biochemical reactions, laying the groundwork for modern enzymology.[4] By the early 1900s, advancements in isolating biological molecules and the advent of journals like Zeitschrift für Physiologische Chemie (founded 1877) solidified biochemistry as a distinct field, blending organic, inorganic, and physical chemistry with biology.[4] This evolution accelerated in the mid-20th century with discoveries in molecular biology, including the structure of DNA in 1953, which illuminated the chemical basis of heredity.[1] Biochemistry encompasses several core areas, including metabolism, which investigates how organisms convert food into energy and building blocks through interconnected pathways like glycolysis and the citric acid cycle; enzymology, focusing on enzymes that accelerate reactions and are classified into six main categories such as oxidoreductases and hydrolases; and molecular genetics, exploring how nucleic acids store and transmit genetic information.[1][5] Additional subfields include structural biochemistry, which analyzes biomolecular architectures using techniques like X-ray crystallography, and bioenergetics, which studies energy flow in cells.[2] These areas highlight biochemistry's role in elucidating dynamic cellular processes, from protein synthesis to membrane transport.[3] The importance of biochemistry lies in its applications across diverse sectors, driving innovations in medicine through drug design targeting metabolic pathways and disease mechanisms, as well as in agriculture via genetically modified crops that enhance nutrient efficiency.[1] In health sciences, it informs pharmacology by revealing how drugs interact with biomolecules, supports toxicology in assessing chemical toxicity, and advances biotechnology through techniques like recombinant DNA for vaccine development.[1] Furthermore, biochemical insights into nutrition and food science improve dietary recommendations and food preservation, while contributions to environmental science address pollutant impacts on ecosystems.[1] Overall, biochemistry provides the molecular framework for understanding and manipulating life processes, underpinning progress in human health, sustainability, and technology.[2]History
Origins and Early Discoveries
The roots of biochemistry emerged from longstanding philosophical debates in the 18th and early 19th centuries between vitalism, which posited that living organisms were governed by a non-physical "vital force" distinct from ordinary chemical processes, and mechanism, which advocated that life could be explained through physical and chemical laws alone.[6] This tension shaped early efforts to study biological phenomena chemically, as vitalists argued that organic compounds could only arise in living systems, while mechanists sought to bridge the gap between inorganic and organic chemistry.[7] A pivotal moment came in 1828 when German chemist Friedrich Wöhler synthesized urea—an organic compound found in urine—from inorganic ammonium cyanate, demonstrating that complex biological molecules could be produced in a laboratory without vital intervention.[8] This experiment challenged vitalist doctrines by showing continuity between inorganic and organic realms, paving the way for viewing life as a series of chemical transformations, though its immediate impact on vitalism's decline was more symbolic than revolutionary.[8] Building on such insights, French chemist Antoine Lavoisier conducted groundbreaking respiration experiments in the 1770s, measuring oxygen consumption and carbon dioxide production in animals and humans, which framed breathing as a form of slow combustion akin to chemical oxidation.[9] These studies established metabolism as a quantifiable chemical process, linking physiological functions to elemental reactions and influencing later biochemical inquiries into energy transformation.[10] In the 1840s, German chemist Justus von Liebig advanced these ideas through his work in physiological or "animal" chemistry, analyzing the chemical composition of foods and bodily fluids to elucidate metabolic pathways in nutrition and respiration.[11] Liebig's experiments demonstrated that animal heat and work arose from the oxidation of carbon and hydrogen in foodstuffs, treating organisms as chemical engines and emphasizing the role of nitrogenous compounds in tissue repair.[12] Toward the late 19th century, Emil Fischer's structural elucidations of sugars like glucose and proteins, including peptide bond formations, provided foundational models for biomolecular architecture, revealing life's building blocks as intricate yet chemically analyzable entities.[13] A culminating discovery occurred in 1897 when Eduard Buchner extracted a yeast press-juice that fermented sugar into alcohol and carbon dioxide without intact cells, proving that enzymatic processes could operate extracorporeally and solidifying biochemistry's focus on isolated chemical mechanisms in biology.[14] These milestones collectively shifted perceptions, portraying vital processes as governed by chemistry rather than mystical forces.[15]Development of Key Concepts and Techniques
The elucidation of the citric acid cycle by Hans Krebs in 1937 marked a pivotal advancement in understanding cellular respiration, demonstrating how acetate is oxidized through a series of enzymatic reactions involving citric acid intermediates to generate energy. Krebs' work, building on earlier observations of carbohydrate metabolism, integrated organic chemistry with physiology and earned him the 1953 Nobel Prize in Physiology or Medicine, shared with Fritz Lipmann for discoveries on coenzyme A. This cycle became a cornerstone for subsequent metabolic pathway research, highlighting the interconnectedness of biochemical processes. In the 1940s and 1950s, Linus Pauling advanced protein structural biology by proposing the alpha-helix and beta-sheet configurations based on X-ray diffraction data and quantum mechanical principles, revolutionizing the understanding of polypeptide folding. Pauling's models emphasized hydrogen bonding's role in secondary structures, influencing later studies on protein function and earning recognition in his 1954 Nobel Prize in Chemistry for chemical bond research. Concurrently, James Watson and Francis Crick's 1953 double-helix model of DNA provided a structural basis for genetic information storage and replication, integrating biochemical and crystallographic evidence from Rosalind Franklin's work. Their discovery, published in Nature, laid the foundation for molecular biology and was honored with the 1962 Nobel Prize in Physiology or Medicine, shared with Maurice Wilkins. Technological innovations in the mid-20th century further propelled biochemical analysis. The development of gel electrophoresis in the 1950s, pioneered by Oliver Smithies for protein separation based on charge and size, enabled precise purification and characterization of biomolecules, earning Arne Tiselius the 1948 Nobel Prize in Chemistry for foundational electrophoretic methods. By the 1970s, nuclear magnetic resonance (NMR) spectroscopy emerged as a non-destructive tool for determining molecular structures in solution, with Kurt Wüthrich's applications to proteins in the 1980s resolving three-dimensional folds and contributing to his 2002 Nobel Prize in Chemistry. These techniques democratized structural biochemistry, allowing detailed studies of enzyme-substrate interactions and nucleic acid conformations. The 2010s introduced CRISPR-Cas9 as a transformative tool for biochemical manipulation, with Jennifer Doudna and Emmanuelle Charpentier's 2012 demonstration of RNA-guided DNA cleavage enabling precise gene editing and functional genomics studies. Their innovation, recognized with the 2020 Nobel Prize in Chemistry shared with Charpentier, facilitated biochemical investigations into gene regulation and protein expression. Nobel recognitions underscored these shifts: the 1975 Chemistry Prize to John Cornforth for his studies on the stereochemistry of enzyme-catalyzed reactions,[16] the 1980 Chemistry Prize to Paul Berg, Walter Gilbert, and Frederick Sanger for their contributions to the biochemistry of nucleic acids, including recombinant DNA and sequencing,[17] the 2023 Physiology or Medicine Prize to Katalin Karikó and Drew Weissman for discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines, and the 2024 Chemistry Prize to David Baker, Demis Hassabis, and John Jumper for computational protein design and protein structure prediction.[18] Post-2000, biochemistry evolved toward integrative approaches like systems biochemistry, which models network-level interactions using computational tools to predict cellular responses. Metabolomics, advanced through high-throughput mass spectrometry and NMR, profiles small-molecule metabolites to map dynamic pathways, as exemplified in global human metabolome projects initiated around 2007. A landmark in predictive modeling came with DeepMind's AlphaFold in 2020, achieving near-experimental accuracy in protein structure prediction via AI, transforming structural genomics and drug design. These developments, incorporating genomic data, have unified biochemistry with systems biology, enabling holistic views of cellular function.Chemical Foundations
Essential Elements and Atoms
Living organisms are primarily composed of a limited set of chemical elements, with six elements—oxygen (O), carbon (C), hydrogen (H), nitrogen (N), calcium (Ca), and phosphorus (P)—accounting for approximately 99% of the mass in the human body. The elements carbon (C), hydrogen (H), oxygen (O), nitrogen (N), phosphorus (P), and sulfur (S), collectively known as CHNOPS, form the foundational building blocks of biological molecules, enabling the complexity and functionality of life. Oxygen dominates by mass at approximately 65%, largely due to its prevalence in water, which constitutes 60-70% of body weight, while carbon makes up about 18%, serving as the structural backbone for organic compounds. Hydrogen and nitrogen follow at roughly 10% and 3%, respectively, contributing to water, organic structures, and key biomolecules like proteins and nucleic acids. Calcium, at approximately 1.5%, is essential for bone mineralization and cellular signaling. Phosphorus and sulfur are present in smaller amounts, at about 1% and 0.25%, yet play critical roles in energy transfer molecules such as ATP and in amino acids like cysteine and methionine. The roles of these elements are tightly linked to their chemical properties. Carbon's versatility stems from its ability to form four stable covalent bonds, arranged in a tetrahedral geometry that allows for diverse three-dimensional structures in biomolecules.[19] This bonding capacity, combined with moderate electronegativity (2.55 on the Pauling scale), enables carbon to create stable chains and rings essential for life's molecular diversity.[20] Hydrogen (electronegativity 2.20) readily forms nonpolar bonds with carbon but polar bonds with more electronegative atoms like oxygen (3.44) and nitrogen (3.04), facilitating hydrogen bonding crucial for molecular interactions.[21] Phosphorus (2.19) and sulfur (2.58) contribute to high-energy bonds and disulfide bridges, respectively, due to their ability to form multiple oxidation states and polar linkages.[22] Besides these major elements, trace elements constitute less than 1% of body mass but are indispensable for specific functions. For instance, iron (Fe), at under 0.01% of total mass, is central to hemoglobin, where it binds oxygen reversibly through redox changes between Fe²⁺ and Fe³⁺ states, enabling efficient transport in blood.[23] Magnesium (Mg), comprising about 0.05%, forms the core of chlorophyll in plants, coordinating with nitrogenous ligands to absorb light for photosynthesis.[24] These elements' low abundance belies their catalytic and structural importance, often as cofactors in enzymes. Isotopic variations of these elements also hold biological significance. Carbon-14 (¹⁴C), a radioactive isotope with a half-life of 5,730 years, is incorporated into biomolecules during life via atmospheric CO₂ fixation and decays post-mortem, allowing radiocarbon dating to determine the age of organic remains up to about 50,000 years old.[25] This technique has revolutionized biochemical studies of ancient ecosystems and molecular turnover rates, providing insights into evolutionary timelines without altering the primary elemental composition.[26]| Element | Approximate % by Mass in Human Body | Key Biological Role |
|---|---|---|
| Oxygen (O) | 65 | Component of water and organic molecules; enables respiration |
| Carbon (C) | 18 | Backbone of organic structures |
| Hydrogen (H) | 10 | In water and C-H bonds for energy storage |
| Nitrogen (N) | 3 | In amino acids and nucleic acids |
| Calcium (Ca) | 1.5 | Structural component in bones and teeth; cellular signaling |
| Phosphorus (P) | 1 | In ATP, DNA, and phospholipids |
| Sulfur (S) | 0.25 | In cysteine, methionine, and coenzymes |
| Iron (Fe) | <0.01 | Oxygen transport in hemoglobin |
| Magnesium (Mg) | 0.05 | Central ion in chlorophyll; enzyme cofactor |