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Skip to 0 minutes and 4 secondsThe biological processes associated with life are achieved by sets of chemical reactions that take place inside cells. The sum of these reactions constitute cellular metabolism and they are organised into metabolic pathways. Two main types of pathways, namely catabolic and anabolic pathways, interconvert large biomolecules, such as fats, carbohydrates and proteins, and their smaller, constituent parts, such as lipids, sugars and amino acids. Catabolic pathways break down large biomolecules, releasing cellular energy in the process, while small biomolecules provide key chemical building blocks for the anabolic pathways, which use up cellular energy as they synthesise the large molecules that compose the cell.

Skip to 0 minutes and 51 secondsCatabolic and anabolic pathways lead to opposing effects, namely the break down or synthesis of large biomolecules, so these types of cellular reactions are carefully coordinated, ensuring that cells function properly without wasting cellular energy. All biochemical reactions involve changes in energy as a result of the breaking and subsequent formation of chemical bonds. Bioenergetics studies the energy transformations that occur as a result of metabolic processes and, during this week of the course, we will look at some of these processes in detail. The energy released during metabolic pathways is used to "do work" within cells, which may relate to homeostasis, the movement of molecules or cells, and the setting up of gradients of molecules.

Skip to 1 minute and 38 secondsMuch energy within cells is tied up in organic molecules, but, when studying bioenergetics, biochemists usually focus on the proportion of energy that becomes "free" to do work. Overall, catabolic pathways release energy and are described as exergonic, whereas anabolic pathways use up energy and are described as endergonic. Through millions of years of evolution, cells have developed efficient ways of temporarily storing energy in the form of high-energy covalent bonds contained in activated carrier molecules. When considering the different metabolic pathways that occur in cells, it's clear that they are interconnected. During metabolism, energetically favorable reactions can be coupled to the energy requiring production of an activated carrier molecule, ensuring that the free energy released can be captured in a useful form.

Skip to 2 minutes and 26 secondsFrom your previous studies, you may already be familiar with the most abundant and versatile activated carrier molecule within all cells, which is called adenosine triphosphate, or ATP. This molecule is widely regarded as the near universal energy currency in cells, providing immediate access to energy for an enormous variety of cellular processes. We will now turn our attention to some of the key biological processes that make ATP because, ultimately, these generate the energy that sustains cellular life. We could review the metabolic pathways that are linked to any of the large biomolecules, such as lipids, nucleic acids or proteins, and in doing so we could review the connections between them.

Skip to 3 minutes and 17 secondsTo keep our discussion relatively straightforward, here we will focus on the metabolism of sugars, which are specific types of carbohydrates. Sugars are broken down by the process of glycolysis in the cytoplasm- a series of ten enzyme catalysed biochemical reactions that converts glucose into two molecules of pyruvate and some additional compounds, such as NADH, another activated carrier. Some of the energy released by glycolysis is coupled to the synthesis of ATP molecules from ADP and inorganic phosphate, by a process known as substrate level phosphorylation.

Skip to 3 minutes and 54 secondsThe pyruvate generated by glycolysis is converted to acetyl CoA, which then feeds into a series of eight enzyme catalyzed steps known as the citric acid cycle, or Krebs cycle, in the mitochondrial matrix. This cyclical pathway generates various activated carrier molecules, such as NAD, FAD and ATP. NAD and FAD donate high energy electrons to a chain of proteins embedded on the inner mitochondrial membrane. This electron transport chain finishes with the electrons being passed on to molecular oxygen, which is reduced to form water. The energy released as a result of the passage of electrons along the respiratory chain is used to transport protons across the inner mitochondrial membrane, which creates an electrochemical proton gradient across the membrane.

Skip to 4 minutes and 44 secondsProtons move back into the mitochondrial matrix through intrinsic channel proteins associated with the enzyme ATP synthase. This process, known as chemiosmosis, releases energy that can be harnessed by the enzyme ATP synthase in order to synthesize ATP from ADP. Using a similar set of biochemical reactions, plants use chemiosmosis to generate ATP in the light-dependent reactions of photosynthesis. Solar energy is captured by chlorophyll pigments of the photosystems in the chloroplasts of plants inducing electron transfer processes that create the electrochemical proton gradient across the thylakoid membrane.

Skip to 5 minutes and 25 secondsSo far, we've only explored a part of the metabolism of carbohydrates, but it's important to remember that cells metabolise different types of compounds, such as proteins, nucleic acids and fatty acid, sometimes to generate energy and sometimes to produce other molecules. For example, fatty acids are catabolised in the mitochondria by a repetitive four step sequence of enzyme catalyzed reactions called oxidation. Each passage through this pathway produces a molecule of FAD, NAD and acetyl CoA and these can feed into the citric acid cycle, or Krebs cycle, and electron transport chain as highlighted above.

Skip to 6 minutes and 11 secondsThe metabolism of nitrogen-containing compounds are also important because nitrogen is a key component of the amino acids of proteins and the nucleotides that are so important for the synthesis of DNA and RNA. The process we have summarised from glycolysis right up to the end of the electron transport chain is commonly referred to as cellular respiration. Importantly, some cells can use molecules other than oxygen to act as the final electron acceptor, allowing them to obtain energy from different environments. For example, some microbes generate metabolic energy using nitrate as a terminal electron acceptor of the electron transport chains. This pathway is of growing significance to biochemists since some intermediates of the process are significant greenhouse gases.

Skip to 6 minutes and 59 secondsAn understanding of bioenergetics is also important for improved awareness of several human diseases that are caused by disruptions in mitochondrial processes, including some forms of cancer and cardiovascular disease. As we will explore further this week, the process of photosynthesis is inspiring solutions to the growing demand for sustainable energy, in the form of novel biofuels and advanced biotechnology products that can convert solar energy into a useful form.

Introduction to metabolism and bioenergetics

Metabolism is central to all cellular life. The video describes the cellular and molecular changes that deliver energy for organisms through different pathways. It highlights two of the most fundamental processes, photosynthesis and cellular respiration.

Focusing on respiration, the video describes how electrons pass along the respiratory chain from one protein to the next and generate a proton gradient across the mitochondrial membrane. As protons move back into the mitochondrial matrix in a process known as chemiosmosis, the molecular machine known as ATP synthase generates ATP. Professor Sir John Walker was one of the researchers who discovered the structure of ATP synthase, winning the Nobel Prize in Chemistry for this research in 1997. Through further studies a detailed understanding of the structure and function of ATP synthase has been obtained - an example of this can be viewed in our Gallery of Molecules.

ATP Walker Screenshot from molecular animation of ATP synthase, prepared by MRC Mitochondrial Biology Unit. Creative Commons Attribution Licence 3.0.

Professor Walker’s research group have also prepared some beautiful animations that illustrate how ATP synthase functions at a molecular level. They illustrate the function and assembly of the mitochondrial ATP synthase.
(To see each animation at its best, you need to click on the “play” button and then make the video full screen, or click on its link in Youtube.)


Technical terms in simplified form

Endergonic

Endergonic reactions are ones in which energy is absorbed from the surroundings. In simple terms, it takes more energy to start the reaction than what is obtained out of it, so the total energy change is a negative net result.

Exergonic

Exergonic reactions are ones in which a positive flow of energy is released to the surroundings. In simple terms, more energy is obtained out of the reaction that is required to start it, so the total energy change is a positive net result.

Respiration

Cellular respiration refers to sets of metabolic reactions that take place in the cells of organisms to convert biochemical energy from nutrients into cellular energy, with the release of waste products. Nutrients that are commonly used in respiration include sugars, amino acids and fatty acids. The most common oxidizing agent used as an electron acceptor in respiration is molecular oxygen (O2), though some organisms can use other chemicals as their final electron acceptor.

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This video is from the free online course:

Biochemistry: the Molecules of Life

UEA (University of East Anglia)