Biochemistry

• 1. Introduction

  ›

  Biochemistry is the study of chemical processes within and relating to living organisms. In 1828, Friedrich Wohler published a paper on his serendipitous synthesis of urea from potassium cyanate and ammonium sulfate. Some regarded that moment as a direct overthrow of vitalism, the long-held belief that living matter held some essential property absent from non-living matter. Before then, it was thought that only living beings could produce the molecules of life. That single experiment opens a much larger story. How did a discipline straddling both chemistry and biology come to explain the inner workings of every living cell? Who first gave it a name, and which experiments earned the title of its birth? And how does a body break down a single sugar molecule to release the energy that keeps it alive? The answers run from the chemical elements that build us to the metabolic pathways that power us.

• 2. Naming A New Science

  ›

  Vinzenz Kletzinsky, who lived from 1826 to 1882, had his Compendium der Biochemie printed in Vienna in 1858, the first use of the term. The word itself derived from a combination of biology and chemistry. Its early history is a contest of claimed origins rather than a single clean founding. In 1877, Felix Hoppe-Seyler used the term, biochemie in German, as a synonym for physiological chemistry. He placed it in the foreword to the first issue of the Zeitschrift fur Physiologische Chemie, the Journal of Physiological Chemistry, where he argued for setting up institutes dedicated to the field. The German chemist Carl Neuberg is often cited as having coined the word in 1903, while some have credited it instead to Franz Hofmeister. The discipline itself reaches back even further than its name. Some trace its beginning to the discovery of the first enzyme, diastase, now called amylase, by Anselme Payen in 1833. Others point to Eduard Buchner's first demonstration of a complex biochemical process, alcoholic fermentation in cell-free extracts, in 1897, as the true birth of biochemistry. Still others cite the influential 1842 work by Justus von Liebig, Animal chemistry, which presented a chemical theory of metabolism, or the 18th century studies on fermentation and respiration by Antoine Lavoisier. Emil Fischer, who studied the chemistry of proteins, and F. Gowland Hopkins, who studied enzymes and the dynamic nature of the field, stand as two examples of early biochemists who helped uncover its layers of complexity.

• 3. The Elements Of Life

  ›

  Around two dozen chemical elements are essential to various kinds of biological life. Strangely, most rare elements on Earth are not needed by life, with selenium and iodine as exceptions, while a few common ones, aluminium and titanium, go unused. Just six elements make up almost 99 percent of the mass of living cells, including those in the human body. They are carbon, hydrogen, nitrogen, oxygen, calcium and phosphorus. Beyond these six major elements, humans require smaller amounts of possibly 18 more. The needs are not identical across all living things. Most organisms share their element requirements, but a few differences separate plants and animals. Ocean algae use bromine, yet land plants and animals do not appear to need any. All animals require sodium, but it is not essential for plants. Plants need boron and silicon, while animals may not need them, or may need only ultra-small amounts. From these starting materials, cells assemble the four main classes of biomolecules that carry out the work of life.

• 4. The Four Biomolecules

  ›

  Carbohydrates outnumber every other known type of biomolecule on Earth. Their two main functions are energy storage and providing structure. Glucose, with the formula C6H12O6, is one of the most important, alongside fructose, the sugar associated with the sweet taste of fruits, and deoxyribose, a component of DNA. Two of the most common polysaccharides, cellulose and glycogen, both consist of repeating glucose monomers. Cellulose forms an important structural part of a plant's cell walls, while glycogen serves as a form of energy storage in animals. Lipids gather under one heading a diverse range of relatively water-insoluble or nonpolar compounds of biological origin. The group includes waxes, fatty acids, phospholipids, sphingolipids, glycolipids, and terpenoids such as retinoids and steroids. In triglycerides, the main group of bulk lipids, one molecule of glycerol combines with three fatty acids, which may be saturated, with no double bonds in the carbon chain, or unsaturated, with one or more. Most lipids are largely nonpolar or hydrophobic, water-fearing, while another part of their structure is hydrophilic, water-loving, making them amphiphilic. Proteins are very large molecules built from monomers called amino acids, of which there are 20 standard ones. Each amino acid carries a side chain, denoted R, and it is this group that makes each one different and shapes the protein's three-dimensional form. The blood serum protein albumin contains 585 amino acid residues. The fourth class, nucleic acids, takes its name from its prevalence in cellular nuclei. The most common are deoxyribonucleic acid, DNA, and ribonucleic acid, RNA, and their monomers, the nucleotides, store and convey genetic information in all living cells and viruses.

• 5. The Power Of Enzymes

  ›

  A reaction that would normally take over 3,000 years to complete on its own might take less than a second with an enzyme. Virtually every reaction in a living cell requires an enzyme to lower the activation energy of the reaction. By doing so, an enzyme can speed up that reaction by a rate of 10 to the 11th power or more. These molecules recognize specific reactant molecules called substrates, then catalyze the reaction between them. The enzyme itself is not used up in the process. It remains free to catalyze the same reaction with a new set of substrates, and its activity can be regulated using various modifiers, enabling control of the cell's biochemistry as a whole. The shape of a protein, including an enzyme, is described in a hierarchy of four levels. The primary structure is the linear sequence of amino acids. Secondary structure concerns local forms such as the coiled alpha-helix or the beta-sheet. Tertiary structure is the entire three-dimensional shape, determined by the amino acid sequence, where a single change can alter everything. The alpha chain of hemoglobin contains 146 amino acid residues. Substituting the glutamate residue at position 6 with a valine residue changes hemoglobin's behavior so much that it results in sickle-cell disease. Quaternary structure concerns proteins with multiple subunits, like hemoglobin with its four. Not every protein, however, has more than one subunit.

• 6. Harnessing Energy

  ›

  Glucose serves as an energy source in most life forms. It is mainly metabolized by a ten-step pathway called glycolysis, which breaks one molecule of glucose into two molecules of pyruvate. Glycolysis also produces a net two molecules of ATP, the energy currency of cells, along with reducing equivalents that convert NAD+ to NADH. This stage requires no oxygen. If no oxygen is available, the NAD is restored by converting pyruvate to lactate, as in humans, or to ethanol plus carbon dioxide, as in yeast. In aerobic cells with sufficient oxygen, as in most human cells, pyruvate is metabolized further. It is irreversibly converted to acetyl-CoA, which then enters the citric acid cycle, releasing carbon atoms as carbon dioxide. The NADH and quinol molecules produced feed into the respiratory chain, an electron transport system that ultimately transfers electrons to oxygen. The released energy is conserved first as a proton gradient across a membrane and then converted to ATP via ATP synthase. This complete oxidation totals 32 molecules of ATP conserved per degraded glucose, two from glycolysis, two from the citrate cycle, and 28 more from the respiratory chain. This is why humans breathe in oxygen and breathe out carbon dioxide. Because oxygen-based oxidation yields far more energy than any oxygen-independent route, complex life is thought to have appeared only after Earth's atmosphere accumulated large amounts of oxygen. When muscles contract vigorously during weightlifting or sprinting, they do not receive enough oxygen and shift to anaerobic metabolism, converting glucose to lactate. The liver later regenerates glucose through gluconeogenesis, a process requiring six molecules of ATP, three times the energy gained from glycolysis. The full loop, from glycolysis during exercise through lactate's journey to the liver and back, is called the Cori cycle.

• 7. The Molecular Neighborhood

  ›

  Genetics, molecular biology, biophysics, and chemical biology surround biochemistry with no firmly defined lines between them. Biochemistry studies the chemistry required for the biological activity of molecules, examining life at the atomic and molecular level. Genetics studies the effect of genetic differences in organisms, often inferred through mutants, organisms that lack one or more functional components compared to the normal wild type. Such knockout studies can be confounded by genetic interactions known as epistasis. Molecular biology studies the molecular underpinnings of biological phenomena. Its central dogma, in which genetic material is transcribed into RNA and then translated into protein, still offers a good starting point for the field, though it has been revised in light of emerging roles for RNA. Several landmark discoveries trace this lineage. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin and Maurice Wilkins were instrumental in solving DNA's structure and suggesting its relationship to the genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork became the first person convicted of murder with DNA evidence, which led to the growth of forensic science. In 2006, Andrew Z. Fire and Craig C. Mello received the Nobel Prize for discovering the role of RNA interference in silencing gene expression.