All organisms require energy to complete tasks; metabolism is the set of the chemical reactions that release energy for cellular processes.
- Explain the importance of metabolism
- All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments; metabolism is the set of the processes that makes energy available for cellular processes.
- Metabolism is a combination of chemical reactions that are spontaneous and release energy and chemical reactions that are non-spontaneous and require energy in order to proceed.
- Living organisms must take in energy via food, nutrients, or sunlight in order to carry out cellular processes.
- The transport, synthesis, and breakdown of nutrients and molecules in a cell require the use of energy.
- metabolism: the complete set of chemical reactions that occur in living cells
- bioenergetics: the study of the energy transformations that take place in living organisms
- energy: the capacity to do work
Energy and Metabolism
All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is the set of life-sustaining chemical processes that enables organisms transform the chemical energy stored in molecules into energy that can be used for cellular processes. Animals consume food to replenish energy; their metabolism breaks down the carbohydrates, lipids, proteins, and nucleic acids to provide chemical energy for these processes. Plants convert light energy from the sun into chemical energy stored in molecules during the process of photosynthesis.
Bioenergetics and Chemical Reactions
Scientists use the term bioenergetics to discuss the concept of energy flow through living systems such as cells. Cellular processes such as the building and breaking down of complex molecules occur through step-by-step chemical reactions. Some of these chemical reactions are spontaneous and release energy, whereas others require energy to proceed. All of the chemical reactions that take place inside cells, including those that use energy and those that release energy, are the cell’s metabolism.
Every task performed by living organisms requires energy. Energy is needed to perform heavy labor and exercise, but humans also use a great deal of energy while thinking and even while sleeping. For every action that requires energy, many chemical reactions take place to provide chemical energy to the systems of the body, including muscles, nerves, heart, lungs, and brain.
The living cells of every organism constantly use energy to survive and grow. Cells break down complex carbohydrates into simple sugars that the cell can use for energy. Muscle cells may consumer energy to build long muscle proteins from small amino acid molecules. Molecules can be modified and transported around the cell or may be distributed to the entire organism. Just as energy is required to both build and demolish a building, energy is required for both the synthesis and breakdown of molecules.
Many cellular process require a steady supply of energy provided by the cell’s metabolism. Signaling molecules such as hormones and neurotransmitters must be synthesized and then transported between cells. Pathogenic bacteria and viruses are ingested and broken down by cells. Cells must also export waste and toxins to stay healthy, and many cells must swim or move surrounding materials via the beating motion of cellular appendages like cilia and flagella.
Teaching the role of mitochondrial transport in energy metabolism
Studies from our laboratories over recent years have uncovered the existence, and established the properties of a variety of mitochondrial transporters. The properties of these transporters throw light on a variety of biochemical phenomena that were previously poorly understood. In particular the role of mitochondrial transport in energy metabolism has been investigated under a variety of physio-pathological conditions. Consistently we describe the procedure to investigate mitochondrial traffic in isolated mitochondria as a model system for students to learn. Here we report some observations that contribute to novel knowledge of the role of mitochondria in glycolysis, urea and purine nucleotide cycle, and nitrogen metabolism with particular reference to the malate/oxaloacetate shuttle and fumarate, glutamine, and lactate metabolism.
Given the enormous rate of accumulation of new knowledge in biochemistry, a question arises as to how teachers can help to ensure that students are conversant with the most recent developments in the subject. In particular, metabolite traffic across the mitochondrial membrane merits special attention in an holistic view of cell biochemistry in which each cell component is a part of a whole with metabolic interactions occurring physiologically. Thus an understanding of the main metabolic pathways in the light of the existence of cross-talk between cytoplasm and mitochondria could lead to an harmonic understanding of cell biochemistry and could stimulate further interest in the study of metabolism in intact cells/organelles.
We have recently dealt with this topic in our review published in Mitochondrion [ 1 ], and will not cover the whole ground again here. Rather, after a brief summary of mitochondrial metabolite transport we will focus our attention on four important questions to which at least partial answers can be given on the basis of published findings.
6.1A: The Role of Energy and Metabolism - Biology
Metabolism is the sum of all types of chemical reaction that take place in the body.
The two types of metabolic reaction are:
In order to occur anabolic reactions require the input of energy. Examples of anabolic reactions include:
- The formation of amino acids in plants (nitrate ions and glucose) which are built up into proteins.
- Converting glucose into starch in plants, or glucose to glycogen in animals.
- The synthesis of lipid molecules.
Catabolic reactions release energy. Examples of Catabolic reactions include:
Catabolic reactions produce waste energy in the form of heat (an exothermic reaction), which is transferred to the environment.
The need to release energy is an essential life process, so respiration continuously takes place in all organisms. The exothermic reaction gives out energy.
Aerobic respiration occurs when Oxygen and glucose molecules react and release energy. The energy is stored in a molecule called ATP.
The symbol equation for aerobic respiration is:
The body uses energy for many purposes including:
- Active transport
- Muscle contraction
- Transmitting nerve impulses
- Synthesising new molecules
- Maintaining a constant body temperature
Anaerobic respiration takes place in the absence of oxygen and is common in muscle cells. It quickly releases less energy than aerobic respiration though the incomplete breakdown of glucose.
Glucose → lactic acid + energy released
In plant and yeast cells, anaerobic respiration produces different products.
Glucose → ethanol + carbon dioxide + energy released
The symbol equation for anaerobic respiration in plant and yeast cells is:
The reaction above is used in brewing and wine making. It is also the basis for the manufacture of spirits.
Response to exercise
Anaerobic respiration will only take place when the muscles are working so hard that the lungs and circulatory system cannot deliver enough oxygen to break down all the available glucose through aerobic respiration.
Anaerobic respiration and recovery
Anaerobic respiration releases energy much faster over short periods of time. It is useful when short intense bursts of energy are required e.g. High intensity exercise (HIT) or the 100 metres sprint.
The incomplete oxidation of glucose causes lactic acid to build up. Lactic acid is toxic and can cause pain, cramp and fatigue.
The lactic acid must be broken down quickly and removed to avoid cell damage and prolonged muscle fatigue.
During exercise your heart rate, breathing rate and breath volume will increase so that sufficient oxygen and glucose is supplied to your muscles, your body can therefore remove lactic acid.
After exercise the process continues when deep breathing will occur until all lactic acid is removed. The repayment of oxygen is called oxygen debt.
Energy Metabolism and its Regulation
Energy metabolism can be defined as the processes that underlie food intake, burning the food to release energy, and storing the excess for the time of energy shortage [10–12] . These processes typically take the form of complex metabolic pathways within the cell, generally categorized as being either catabolic or anabolic. These events then provide a source of energy at the cellular level. As the organisms evolved from simpler metabolisms in invertebrates to the more complex ones in vertebrates, the organisms faced three challenges. First, they needed a mechanism to regulate how much excess energy can be stored and in which form second, there arose a need for specialized cell types to store excess energy typically in the form of fat so that its deposition can be better regulated and third, they needed a mechanism to coordinately adjust energy flux through various organs in response to changing nutritional status. Organisms coped with these three challenges by storing fat, predominantly, in the specialized cell types called adipocytes, and regulated the energy metabolism status of different tissues/organs through hormonal signals that acted on multiple organs to coordinate their energy flux [13,14] . Regulation of whole body energy metabolism and bone mass through an adipocyte-secreted hormone called leptin provides a beautiful illustration of how multiple functions are coordinated by the energy stores of the body—the adipose tissue, and how organs in turn regulate this store.
6.1A: The Role of Energy and Metabolism - Biology
Metabolism and Cellular Respiration
What is metabolism?
All living things must have an unceasing supply of energy and matter. The transformation of this energy and matter within the body is called metabolism. Metabolism includes two different types: catabolism and anabolism. Catabolism is destructive metabolism. Typically, in catabolism, larger organic molecules are broken down into smaller constituents. This usually occurs with the release of energy. Anabolism is constructive metabolism. Typically, in anabolism, small precursor molecules are assembled into larger organic molecules. This always requires the input of energy.
Anabolism and catabolism Pathways
Anabolism is the synthesis of complex molecules from precursors. This includes synthesis of proteins, carbohydrates, nucleic acids and lipids, usually from their building block monomers. Catabolism is the breakdown of complex molecules into smaller precursors from which they are synthesized. It is a reversed process of anabolism. When cells have excess resources such as food and extra energy, anabolism occurs to store unused nutrients for later use. When cells are deficient for food or energy, catabolism occurs to break down the stored nutrients for the body to use.
Energetics of biological Reactions
Biological energy is the capacity to run biochemical reactions to enable the cells to do their work. Free energy (G) relates temperature, enthalpy and entropy. Free energy is used to determine if the reaction is spontaneous at a specific temperature.
Determining spontaneity of a process
Free energy describes whether a reaction will occur spontaneously. The First Law of Thermodynamics states that energy is conserved: energy can neither be created nor destroyed. The Second Law of Thermodynamics states that the work produced from a given energy can never be 100% efficient. In metabolism, reactions which are spontaneous are favorable because these run automatically and release free energy. Every reaction has an activation energy, which describes an energy barrier that is overcome every time the reaction occurs. Most of the reactions in the cell require enzymes. Enzymes are proteins to speed up reactions by grabbing onto reactants to bring them closer together. Reactants which are closer together can reach activation energy more easily. Thus, enzymes lower activation energy and speed up the reaction.
ATP is the energy currency of all cells. Most of the reactions in the cell require ATP. ATP is energy rich. When the energy is used by a reaction, ATP breaks up into ADP and Pi. In order to use the energy again, ADP and Pi must be changed back into ATP. This requires energy. Non-spontaneous reactions requires energy, and this is often done by coupling this reaction with an ATP breaking down reaction, the combined free energy will be negative and therefore enables the overall reaction.
Cellular respiration is a series of metabolic processes which all living cells use to produce energy in the form of ATP. In cellular respiration, the cell breaks down glucose to produce large amounts of energy in the form of ATP. Cellular respiration can take two paths: aerobic respiration or anaerobic respiration. Aerobic respiration occurs when oxygen is available, whereas anaerobic respiration occurs when oxygen is not available. The two paths of cellular respiration share the glycolysis step. Aerobic respiration has three steps: glycolysis, Krebs cycle, and oxidative phosphorylation. During glycolysis, glucose is broken down into pyruvate and produces 2 ATP. The Krebs cycle is also known as TCA cycle which contains a series of Redox reactions to convert pyruvate into CO2 and produce NADH and FADH2. During oxidative phosphorylation, NADH and FADH2 are used as substrate to generate a pH gradient on mitochondria membrane which is used to generate ATP via ATP synthase. Anaerobic respiration contains two steps: glycolysis and fermentation. Fermentation regenerates the reactants needed for glycolysis to run again. Fermentation converts pyruvate into ethanol or lactic acid, and in the process regenerates intermediates for glycolysis.
Metabolism includes catabolism and anabolism. Anabolism is the synthesis of complex molecules from precursors, while catabolism is the breakdown of complex molecules into smaller precursors from which they are synthesized. All these pathways involve biochemical reactions. Free energy describes whether a reaction will occur spontaneously. In metabolism, reactions which are spontaneous are favorable because these run automatically and release free energy. Every reaction has an activation energy which can be lowered down by enzymes. Enzymes do this by bringing the reactants closer together. ATP is the energy currency of all cells. Most of the reactions in the cell require ATP. A non-spontaneous reaction can be coupled to ATP hydrolysis reaction to enable the overall reaction release free energy and therefore become favorable. ATP is generated by cellular respiration, which contains fermentation (anaerobic respiration) and the Krebs cycle (aerobic fermentation).
Metabolic rate means the amount of chemical energy liberated in the body per unit time. Chemical energy is measured in calories (the amount of energy that will heat 1 gram [0.035 ounce] of water by 1 degree Celsius [1.8 degrees Fahrenheit]), although a calorie is such a small unit that it is more practical to think in terms of kilocalories (kcal). One kilocalorie is 1,000 calories, or what dietitians (and food labels) call a Calorie with a capital C. Metabolic rate is generally expressed in kcal/hour or kcal/day. A person's metabolic rate can be estimated by having him or her breathe from a spirometer, a device that measures the person's rate of oxygen consumption. Every liter of oxygen consumed represents the release of approximately 4.82 kcal of energy from organic compounds such as fat and glycogen. This ratio varies, however, depending on what type of energy-storage molecules the person is oxidizing at the time of measurement.
Metabolic rate depends on such variables as physical activity, mental state, fed or fasting status, and hormone levels, especially thyroid hormone. The basal metabolic rate (BMR) is a standard of comparison that minimizes such variables. It is measured when a person has not eaten for twelve to fourteen hours and is awake, relaxed, and at a comfortable temperature. It is not the minimum rate needed to keep a person alive the metabolic rate is lower than the BMR when one is asleep. Total metabolic rate (TMR) is the BMR plus the added energy expenditure for movement and other activities. Metabolic rate is elevated not only by physical activity but also by eating, anxiety, fever, pregnancy, and other factors. Factors that reduce the TMR below normal include depression, apathy, and prolonged starvation.
The TMR is higher in children than in adults. Consequently, as people approach middle age, they often gain weight even with no change in food intake. Weight-loss diets tend to be frustrating not only because most of the initial weight loss is water, which is quickly regained, but also because the TMR declines with time as the diet progresses, fewer calories are burned and one begins to synthesize more fat even with a stable caloric intake.
The average young adult male has a BMR of 2,000 to 2,500 kcal/day, and the average female slightly lower. Thus, one must consume this many calories per day just to sustain such essential processes as the heartbeat, respiration, brain activity, muscle tone , renal function, and active transport through cell membranes. The central nervous system accounts for about 40 percent of the BMR and the muscular system for 20 to 30 percent. Even a relatively sedentary lifestyle requires another 500 kcal/day, and hard physical labor, as in farming or manufacturing, may require up to 5,000 kcal/day.
Biophysics 354Lecture 1
In this course, we will explore the evolution of the energy conversion apparatus, the mechanisms of energy conversion, and the physicochemical tools necessary for a deeper understanding of those mechanisms. The main emphasis will be on the major pathways for energy conversion, - photosynthesis and respiration, - with some consideration of the metabolic reactions that link these processes to the main biochemistry and physiology of the organism.
The molecular basis of energy transduction
- The photochemical reaction centers of bacterial and green plant photosysnthesis have provided a playground for testing theories of electron transfer, in which the structures have provided details of distance and local milieu essential for an understanding of the factors that determine rates, as measured by ultra-fast spectroscopic approaches. The lessons from these model systems are already being applied widely to other electron transfer processes.
- Structures of light-harvesting complex have yielded new ideas and insights into excitation transfer processes and exciton energy funnelling.
- The structures of the ATP synthase complex have revealed the smallest turbine-driven motor, confirming ideas based on detailed analysis of data from earlier biochemical and biophysical approaches. This device promises to spawn a whole field of nanotechnology, in which the nanomotor is linked to machinery operating on a molecular scale.
- Structures for the respiratory complexes have opened new possibilities for understanding the coupling of electron transfer to proton pumping. The bc1 complex has revelaed a new mechanism for electron transfer over distance, - a movement of the mobile extrinsic domain of the iron sulfur protein through 25 nm, - and hinted at other dynamic features. Cytochrome oxidases are showing us novel mechanism for coupling electron transfer to local protonic potential, through deep proton wells into the catalytic core.
- Structures of bacteriorhodopsin have provided us with the most detailed dynamic picture of a photomolecular pump, in which protons activated through photoisomerization are switched between proton conduction pathways in and out of the protein.
Mitochondria, - their role in cell death and aging
- The controlling function of mitochondrial integrity in apoptosis, - programmed cell death. The ability of the body to get rid of cells that go wrong is critical to control of cancer, and to the efficient recycling of macromolecular constituents. The mitochondria, through release of factors that turn on the cascade of reactions leading to apoptosis, are of central importance in determining how and when the cell recognizes that it's time to go.
- The role of the respiratory chain in generation of reactive oxygen species (ROS), - the main causal agents in DNA damage leading to cellular aging. Two of the main complexes of the respiratory chain, - Complex I, or NADH:ubiquinone oxidoreductase, and Complex III, or the bc1 complex, - are the main sites in the cell at which O2 is reduced to superoxide anion, the molecule from which the ROS are derived. Because mitochondria have a less efficient DNA repair mechanism than the nucleus, they are the main victims of this damage. As a consequence, your mitochondria become disfunctional as you age, resulting in loss of energy, and eventually death by "cellular suffocation". Your mitochondrial energy metabolism is essential for survival, but the mechanism has built-in this suicidal reaction. If nothing else kills you, your mitochondria will, - a classical "Catch-22" of cellular metabolism.
Photosynthesis, ecology and global warming
All of the above are good reasons for a renewed interest in biological energy conversion. The important fact is that these processes are central to all living processes, and have been thoughout evolution. The invention of oxygenic photosynthesis, and the consequent development of an aerobic biosphere, and the adaptation of organsims to this potentially poisonous reagent through the invention of respiration, were crucial in the evolution of the eukaryotic cell, the modern biosphere, and its animal and plant inhabitants. You cannot understand biology if you don't understand biological energy conversion.
10.2.1 Enzyme Active Site and Substrate Specificity
The chemical reactants to which an enzyme binds are called the enzyme’s substrates. There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule.
The location within the enzyme where the substrate binds is called the enzyme’s active site. Since enzymes are proteins, there is a unique combination of amino acid side chains, which creates a very specific chemical environment within the active site. This specific environment is suited to bind to a specific substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates, enzymes are known for their specificity. The “best fit” results from the shape and the amino acid functional group’s attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction.
Since enzymes are proteins, their shape is sensitive to variations in temperature and pH. Increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes to denature. Likewise, pH can also affect enzyme function. Enzymes are suited to function best within a certain pH range, and extreme pH values can cause enzymes to denature.
Induced Fit and Enzyme Function
For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit (Figure 10.5). The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an ideal binding arrangement between the enzyme and the transition state of the substrate. This ideal binding maximizes the enzyme’s ability to catalyze its reaction.
Enzymes will always return to their original state once the reaction is complete. One of the hallmark properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme is finished catalyzing a reaction, it releases its product(s).
Figure 10.5 According to the induced-fit model, both enzyme and substrate undergo dynamic conformational changes upon binding. The enzyme contorts the substrate into its transition state, thereby increasing the rate of the reaction.
Role of NCoR1 in mitochondrial function and energy metabolism
Mitochondrial number and shape are constantly changing in response to increased energy demands. The ability to synchronize mitochondrial pathways to respond to energy fluctuations within the cell is a central aspect of mammalian homeostasis. This dynamic process depends on the coordinated activation of transcriptional complexes to promote the expression of genes encoding for mitochondrial proteins. Recent evidence has shown that the nuclear corepressor NCoR1 is an essential metabolic switch which acts on oxidative metabolism signaling. Here, we provide an overview of the emerging role of NCoR1 in the transcriptional control of energy metabolism. The identification and characterization of NCoR1 as a central, evolutionary conserved player in mitochondrial function have revealed a novel layer of metabolic control. Defining the precise mechanisms by which NCoR1 acts on energy homeostasis will ultimately contribute towards the development of novel therapies for the treatment of metabolic diseases such as obesity and type 2 diabetes.
Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP + ], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13 C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in energy metabolism, which are specific for distinct mitochondiral/environmental toxins, are not bystanders to energy failure but also contribute significant to cell death progression.