Jennifer Moyle (April 30, 1921 - August 1, 2016) [1] [2] was a British biochemist who helped discover the chemiosmotic mechanism of ATP synthesis.
She also conducted research on the properties of purified isocitric enzymes [3] and calcium import in the mitochondria during cellular respiration. [4]
Jennifer Moyle was born in Norwich, England and attended Norwich High School for Girls. [5] [6] She was the daughter of S.H. Leonard Moyle and Olive M. Dakin. She had a sister named Vivian, who also studied biochemistry.
Moyle began schooling at Norwich High School for Girls in 1926 where she remained until entering Girton College of Cambridge University in 1939. [7] While studying there, she earned a "Title of Bachelor of Arts Degree", [8] the equivalent of modern-day Bachelor of Arts, in 1942. She specialized in Biochemistry, and also attended many lectures on philosophy.
In 1955, Moyle began her PhD work at the University of Edinburgh, and was awarded a PhD in zoology in 1958.
Moyle conducted a lot of research regarding cellular respiration, [4] oxidative phosphorylation, [9] and properties of purified isocitric enzymes. [10] She was a major contributor to the development of the chemiosmotic theory regarding ATP synthesis. [11]
Shortly after earning her degree, Moyle entered the Auxiliary Territorial Service during World War II. She went into military intelligence, where she soon become an intelligence officer in MI8. There, she was promoted to second in command of a section dealing with intelligence obtained from ciphers breaking German codes. [12]
After World War II, she continued service for another year helping teach servicemen how to return to civilian life. [7]
Moyle began her career in biochemistry research in 1964 when she joined a Cambridge biochemistry lab. She began as an assistant to Marjory Stephenson, but after a few years Stevenson introduced Moyle to Peter D. Mitchell, with whom Moyle worked for the majority of her research career. Jennifer's main research focus was cellular respiration. for a short period, Moyle worked with Malcolm Dixon, and the two focused their work on the purification of isocitric enzymes. [12]
Jennifer Moyle published an article on the properties of purified isocitric enzymes in August 1956 with Malcolm Dixon. [10] The article describes the chemical and physical properties of isocitric enzymes, various reactions they are involved in, causes for their inactivation, and a hypothesis for the mechanism of reaction. [10] Moyle and Dixon authored another paper regarding the isocitric enzyme Triphosphopyridine Nucleotide-linked isoCitric Dehydrogenase-Oxalosuccinic Carboxylase. [13] The paper outlines the proper method of the purification of that enzyme.
One of Moyle's major contributions to the field of biochemistry is her contribution to the development of the chemiosmotic theory. Moyle conducted research with Peter Mitchell, at Glynn House, on chemiosmotic reactions and reaction mechanisms, which led to the development of the theory in 1967. [11] The chemiosmotic theory explained the mechanism for oxidative phosphorylation, stating that ATP synthesis requires chemiosmosis to function. [9] The proton gradient across the inner membrane of the mitochondria is created by the electron transport chain. This causes protons to re-enter the mitochondrial matrix through the protein ATP synthase. The movement of protons through this enzyme causes mechanical movement and a conformational change in the enzyme that combines ADP and inorganic phosphate to produce ATP. [9] The proposal of the chemiosmotic theory was not accepted in the scientific community for over ten years. When it finally was accepted, Peter Mitchell received a Nobel prize for their work. While the Nobel committee recognized Moyle's contributions, she did not receive a Nobel prize.
The chemiosmotic theory was radical at the time, and it was not immediately accepted by the scientific community. One experiment that Moyle and Mitchell conducted in 1967 was an investigation of ways to improve the precision at which the quotients of translocation of a proton to oxygen can be measured, and what the optimum conditions are for these measurements. [14] Their goal was to improve the precision of that measurement in order to allow others to confirm their findings in the proposed chemiosmotic hypothesis. They conducted this experiment because the arrangement of the electron transport chain was only a hypothesis at the time, and it had been inferred from a quotient of protons translocated to oxygen in the chain (→H+/O). [14] Moyle and Mitchell isolated mitochondria from a rat liver, measured pH displacement across the mitochondrial membrane, and computed the relationship between proton translocation and changes in pH. They found that the pulses of acidification of the inner membrane space of the mitochondria are due to the transport of H+ ions from the mitochondrial matrix into the inner membrane space, and can't be attributed to the formation and breakdown of an intermediate as was previously hypothesized. [14] Their work provided sufficient detail for others to reproduce their experiment and confirm their previous findings regarding the chemiosmotic theory.
An article published jointly with Peter Mitchell in 1977 outlines their work regarding calcium import into mitochondria in the rat's liver during cellular respiration. In the article, they state that this import of calcium happens electrophoretically, and that evidence had already been obtained showing that one electric charge is translocated through a lanthanide-sensitive transporter system per a single calcium ion (Ca2+) imported. Moyle and Mitchell isolated rat liver mitochondria to investigate their hypothesis that the calcium transporter is in fact a calcium phosphate transporter, defined in the article as a "(Ca2)4+--HPO42- symporter." Their results were consistent with their hypothesis, showing that a lanthanide-sensitive (Ca2)4+--HPO42- symporter that is insensitive to NEM and mersalyl catalyzed calcium translocation in the mitochondria of the rat liver. [4]
Jennifer Moyle and Peter Mitchell were research colleagues for over thirty years, beginning around 1948 and continuing until Moyle's retirement in 1983. [12] They worked together on many research projects, including the development of the chemiosmotic theory. Moyle designed many of the experiments that were fundamental in testing the theory's hypothesis, and she helped Mitchell win the Nobel Prize in chemistry in 1978. [11]
Moyle and Mitchell also cofounded charitable research company known as Glynn Research Ltd., a research institute that promoted biological research from 1964 to 1987. [15]
Jennifer Moyle and Malcolm Dixon worked together for roughly two years. During this time together, they researched the properties of purified isocitric enzymes and published their findings. [10]
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. It is also a precursor to DNA and RNA, and is used as a coenzyme. A human adult processes around 50 kg of ATP daily.
The citric acid cycle —also known as the Krebs cycle, Szent-Györgyi-Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.
A mitochondrion is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name.
Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this electron transfer with the transfer of protons (H+ ions) across a membrane. The electrons that are transferred from NADH and FADH2 to the ETC involves four multi-subunit large enzymes complexes and two mobile electron carriers. Many of the enzymes in the electron transport chain are embedded within the membrane.
Cellular respiration is the process by which biological fuels are oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into ATP, and then release waste products.
Christian René Marie Joseph, Viscount de Duve was a Nobel Prize-winning Belgian cytologist and biochemist. He made serendipitous discoveries of two cell organelles, peroxisome and lysosome, for which he shared the Nobel Prize in Physiology or Medicine in 1974 with Albert Claude and George E. Palade. In addition to peroxisome and lysosome, he invented scientific names such as autophagy, endocytosis, and exocytosis in a single occasion.
Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H+) across a membrane during cellular respiration or photosynthesis.
Peter Dennis Mitchell FRS was a British biochemist who was awarded the 1978 Nobel Prize for Chemistry for his theory of the chemiosmotic mechanism of ATP synthesis.
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study of thousands of different cellular processes such as cellular respiration and the many other metabolic and enzymatic processes that lead to production and utilization of energy in forms such as adenosine triphosphate (ATP) molecules. That is, the goal of bioenergetics is to describe how living organisms acquire and transform energy in order to perform biological work. The study of metabolic pathways is thus essential to bioenergetics.
The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. It also refers to the space between the inner and outer nuclear membranes of the nuclear envelope, but is often called the perinuclear space. The IMS of mitochondria plays a crucial role in coordinating a variety of cellular activities, such as regulation of respiration and metabolic functions. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function.
Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most bacteria. The name "cardiolipin" is derived from the fact that it was first found in animal hearts. It was first isolated from the beef heart in the early 1940s by Mary C. Pangborn. In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane, where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
Efraim Racker was an Austrian biochemist who was responsible for identifying and purifying Factor 1 (F1), the first part of the ATP synthase enzyme to be characterised. F1 is only a part of a larger ATP synthase complex known as Complex V. It is a peripheral membrane protein attached to component Fo, which is integral to the membrane.
The phosphate/oxygen ratio, or P/O ratio, refers to the amount of ATP produced from the movement of two electrons through a defined electron transport chain, terminated by reduction of an oxygen atom.
A mitoplast is a mitochondrion that has been stripped of its outer membrane leaving the inner membrane and matrix intact.
Bernhard Kadenbach was a German biochemist with main research in structure and function of the mitochondrial cytochrome c oxidase, who worked as a professor in the chemistry department of Philipps-Universität Marburg.
André Tridon Jagendorf was an American Liberty Hyde Bailey Professor Emeritus in the Section of Plant Biology at Cornell University who is notable for providing direct evidence that chloroplasts synthesize adenosine triphosphate (ATP) using the chemiosmotic mechanism proposed by Peter Mitchell.
In the field of enzymology, murburn is a term coined by Kelath Murali Manoj that explains the catalytic mechanism of certain redox-active proteins. The term describes the equilibrium among molecules, unbound ions and radicals, signifying a process of "mild unrestricted redox catalysis".