krebs cycle by Andrew Twist

Metabolism [muh-tab-uh-liz-uhm] is the name given to the chemical reactions which keep an organism alive. A chemical reaction is the transformation of one set of chemical substances to another. Organisms require myriad reactions to grow, reproduce, maintain their structures, and respond to their environments. These reactions are catalyzed by enzymes (aided by reusable proteins that change the rate of chemical reactions).

Most of the structures that make up animals, plants, and microbes are made from three basic classes of molecule: amino acids (the building blocks of proteins), carbohydrates (sugars), and lipids (fats). As these molecules are vital for life, metabolic reactions either focus on making these molecules during the construction of cells and tissues (anabolism), or by breaking them down and using them as a source of energy, by their digestion (catabolism).

The chemical reactions of metabolism are organized into ‘metabolic pathways,’ or cycles, like the Krebs cycle, which is used by all aerobic (oxygen requiring) organisms to generate energy. One chemical is transformed through a series of steps into another chemical by a series of enzymes. The metabolic system of an organism decides which substances it finds nutritious and which poisonous. For example, some prokaryotes (primitive, single-celled organisms) use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The speed of metabolism, the ‘metabolic rate,’ influences how much food an organism will need, and how it is able to get that food. A striking feature of metabolism is the similarity of the basic metabolic pathways and components between even vastly different species. For example, a set of carboxylic acids that are part of the Krebs cycle are present in all known organisms, from bacteria to humans. These striking similarities in metabolic pathways are likely due to their early appearance in the evolution of life, and kept because of their efficiency.

The term metabolism is derived from the Greek ‘Metabolismos’ for ‘change,’ or ‘overthrow.’ The first documented references of metabolism were made by Syrian physician Ibn al-Nafis in his 1260 work ‘The Treatise of Kamil on the Prophet’s Biography,’ which included the following phrase ‘Both the body and its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change.’ The history of the scientific study of metabolism spans several centuries and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Italian physiologist Santorio Santorio in 1614 in his book ‘Ars de statica medicina.’ He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called ‘insensible perspiration.’

In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue. In the 19th century, when studying the fermentation of sugar to alcohol by yeast, French microbiologist Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called ‘ferments.’ He wrote that ‘alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells.’ This discovery, along with the publication by German chemist Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea, and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.

It was the discovery of enzymes at the beginning of the 20th century by German zymologist Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry. The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle (which is now commonly known as the ‘Krebs Cycle’) and the glyoxylate cycle. Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy, and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.

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