In every cell, a large number of various chemical reactions, which form the metabolic pathways of the successive transformation of some compounds into others, constantly occurs. Metabolism is the aggregate of all metabolic pathways that take place in the cells of the body. Metabolism is a key process that enables adequate functioning of human organism and energy supply. It is tightly regulated and ideal functioning of all metabolic pathways is one of the conditions of homeostasis. Nevertheless, there are many metabolic diseases and dysfunctions that could be addressed. Metabolism is tightly interconnected with aging, physiological adaptations, and, thus, must be flexible in disease. Metabolism is the basis of human body homeostasis as it provides chemical transformations to synthesize energy and nutrients, keep proper water and heat balance in the organism; however, the amendments to metabolic pathways could provide more benefits.
Structure and Organization
Metabolism provides the energy needs of the body, which is achieved by extracting energy from the nutrients entering the body and converting it into forms of the macroergic, including ATP and other molecules, and reduced compounds, such as NADP, 4-nicotinamide-amino-adenine dinucleotide phosphate (Lanham-New, MacDonald, & Roche, 2011). The produced chemical energy is used for essential needs of the cell: protein synthesis, production of nucleic acids and lipids, and synthesis of components of cell membranes and new cell organelles. Metabolism is necessary for performing mechanical, chemical, osmotic, electrical functions, and ion transport.
Typically, the substance is converted into a product or products through a series of intermediates, in the formation of which several enzymes, acting in sequence one by one, participate. This sequence of reactions represents the so-called metabolic pathway (Lanham-New, MacDonald, & Roche, 2011). Many processes are happening in the cell at the same time. The reactions proceed in a coordinated manner and subject to strict regulation, which is explained by the specific nature of the enzymes. One enzyme usually catalyzes only one reaction. Thus, the enzymes serve to regulate the reactions occurring in the cell and ensure their proper rate.
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By keeping proper metabolism, the body delivers the plastic substances necessary for biosynthesis, construction, and renewal of biological structures. In the metabolism, there are two interconnected multidirectional processes, such as anabolism, which is based on the processes of assimilation, and catabolism, which includes the processes of dissimilation (Lanham-New, MacDonald, & Roche, 2011). The interconnection between the processes of catabolism and anabolism depends on the unity of biochemical transformations, providing energy for all processes of vital activity and constant renewal of body tissues. Catabolism is the driving force of life (Lanham-New, MacDonald, & Roche, 2011).
There are three main stages of metabolism. The first stage is the consecutive splitting of chemical components of food in the gastrointestinal tract to low molecular structures and the subsequent absorption of the formed simple chemicals. Products are transferred into the blood or lymph. Cleavage of proteins, fats, and carbohydrates occurs under the influence of specific enzymes. Proteins are cleaved by peptides to amino acids, fats are transformed by lipases to glycerol and fatty acids, complex carbohydrates are divided by amylases into monosaccharides (Lanham-New, MacDonald, & Roche, 2011).
The second stage of metabolism combines the transformation of amino acids, monosaccharides, glycerol, and fatty acids (Lanham-New, MacDonald & Roche, 2011). In the process of intermittent metabolism, proteins, carbohydrates, fats and their complexes are synthesized, similarly to further transformation of amino acids, glucose, glycerol, and fatty acids. The process of interchange leads to the formation of a few key compounds that cause a cross-correlation between individual metabolic pathways, as well as between the processes of synthesis and decay. Such a compound, for example, is pyruvic acid, a common product of the decomposition of carbohydrates, fats, and the nitrogen-free residue of certain amino acids, which acts as a link between carbohydrates, fats, and most amino acids (Lanham-New, MacDonald, & Roche, 2011). Moreover, pyruvic acid can serve as a product for the synthesis of carbohydrates and fats, and also participate in the re-amination of amino acids (Lanham-New, MacDonald, & Roche, 2011). Intermediate metabolic processes lead to the synthesis of species-specific proteins, fats, carbohydrates and their complexes, including nucleotides and phospholipids, and result in the formation of constituent parts of the body (Lanham-New, MacDonald, & Roche, 2011). Additionally, these processes are the main source of energy. In the human body, the conservation and use of energy is done by converting it into the energy of the macroergs. It is ATP that accumulates 60-70% of all energy released during the intermittent exchange of nutrients (Lanham-New, MacDonald, & Roche, 2011). Only 30-40% of the energy released during the oxidation of proteins, fats, and carbohydrates turns into heat energy and leaves the body in the process of heat energy (Lanham-New, MacDonald, & Roche, 2011).
The third stage is the formation and isolation of the final products of metabolism. Nitrogen-containing products are excreted in urine, feces, and in small amounts through the skin. Carbon is released mainly in the form of CO2 through the lungs and in part with urine and feces. Isolation occurs mainly in the form of water through the lungs and skin, as well as with urine and feces. The same way mineral compounds are excreted.
The processes of metabolism of proteins, fats, and carbohydrates have its specific features. There are general patterns that allow to distinguish three stages of metabolism, such as processing of nutrients in organs known as digestion, interstitial metabolism, and processing of the end products of metabolism.
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Regulation of protein metabolism at the cellular level takes place due to the “automatic principle” of conjugation of intracellular metabolic reactions, in which the level of reaction substrates, content of synthesis products, and enzymatic activity are closely related and provide the optimal level of processes responsible for the synthesis and cleavage of the protein. Regulatory influence of the central nervous system on the processes of protein synthesis and degradation is achieved both due to direct neurotrophic influences and indirect purposeful change in the activity of various glands of the endocrine system.
Hypothalamus as the highest center of the regulation of metabolism, including protein metabolism, provides control over the functioning of the endocrine organs subordinated to it through production and allocation of the corresponding neurohormones, such as liberins and statins (Lanham-New, MacDonald, & Roche, 2011). This action, in its turn, leads to the production of hormones that ensure the accumulation of protein (anabolic) or its intensive expenditure (catabolic). Anabolic hormones are released in the pituitary gland, sex glands, pancreas, or thyroid gland, but in any case the effects of these hormones are coordinated with the general program of the functioning of the body. Protein metabolism changes with strong emotional stimulation, in sleep, under hypnotic conditions, and even conditionally-reflexively, in anticipation of a significant expenditure (wear) of structural proteins. The growth hormone (STH) has a powerful anabolic effect during the growth period in youth, providing accumulation of protein mass of all organs and tissues and the corresponding development of the skeleton. Insulin has an anabolic effect both directly affecting the processes of transcription and translation, and indirectly due to the intensification of transport processes on the cell membrane, increasing the entry into the cell of amino acids. Catabolic hormones include adrenocorticotropic hormone of the pituitary gland which exerts its influence on the cortical substance of the adrenal gland. This example shows how protein metabolism and hormones are interconnected.
Lipids of the human body are mainly neutral esters of glycerol and higher fatty acids, such as triglycerides, phospholipids, and sterols (Lanham-New, MacDonald, & Roche, 2011). The plastic function of lipids in the body is performed mainly by phospholipids, cholesterol, and fatty acids. These molecules function as structural components of cell membranes or lipoproteins, which are precursors of the synthesis of steroid hormones, bile acids, and prostaglandins (Lanham-New, MacDonald, & Roche, 2011). In the small intestine under the influence of bile acids, emulsification of fat to chylomicrons occurs (Lanham-New, MacDonald, & Roche, 2011). Bile acids form water-soluble complexes with fatty acids, which ensure the penetration of fatty acids into the epithelium of the intestinal wall.
The human body receives carbohydrates, mainly in the form of vegetable starch polysaccharide and in a small amount in the form of a glycogen. In the digestive tract, their cleavage is done to the level of monosaccharides, such as glucose, fructose, lactose, galactose. Monosaccharides are absorbed into the bloodstream, and hepatic cells enter through the portal vein. Here fructose and galactose is converted into glucose. The intracellular glucose concentration in hepatocytes is close to its concentration in the blood. With excess intake of glucose in the liver, it is phosphorylated and converted to glycogen
Almost all biochemical reactions in the body take place in aqueous solutions of the complex substances that constitute the basis of living matter. Due to the polarization of the water molecule, it ensures its interaction with other charged molecules in hydration processes. The degree of solubility of electrolytes and non-electrolytes depends on the ratio of polar (hydrophilic) and non-polar (hydrophobic) groups in their molecules. In the aqueous phase, nutrients are absorbed, and the end products of metabolism are removed from the body. Water is the basis of intracellular metabolism. Having high osmotic activity, electrolytes actively participate in the processes of water metabolism. Biological membranes, including cell membranes and capillary walls, are characterized by a semi-permeability. They are permeable to water and impermeable to large molecules, such as polysaccharides and some cations. With an increase in osmotic pressure, water easily penetrates into this area and compares the concentrations of osmotically active substances. Since under normal conditions the osmolality of biological fluids is equal, the amount of water in the extracellular fluid and inside the cells is maintained within certain limits (Lanham-New, MacDonald, & Roche, 2011). In general, metabolism of water is necessary for vitamin and microelements metabolism.
Metabolism and Homeostasis
Homeostasis is the stability of biological systems and returning it to constancy, like pendulum. In the event that homeostasis suffers from a disorder, the cells are damaged, which can lead to their death. To maintain homeostasis, nutrients and energy are required. The cell is engaged in the synthesis of the necessary substances, and also produces the disintegration of unnecessary substances. The resulting carbohydrates, fats, and proteins are used to construct cellular structures, which require energy to create. Metabolism is regulated in such a way that the internal environment of the body optimally corresponds to external conditions, but the level of metabolic processes has a certain relatively constant range, corresponding to adaptive reactions. External conditions tend to cause changes, and the body continuously adapts to these processes, providing internal environment responses within a constant range.
The intensity of metabolism is determined by the need for cells in certain substances or energy. Its regulation is conducted in four ways. First, the total rate of reactions of a particular metabolic pathway is determined by the concentration of each of the enzymes of this pathway, pH of the medium, intracellular concentration of each of the intermediates, and concentration of co-factors and co-enzymes. Second way is represented by the activity of regulatory or allosteric enzymes, which usually catalyze the initial stages of metabolic pathways. Most of them are inhibited by the final product of this pathway, and this kind of inhibition is called “feedback principle.” Third way is a genetic control, which determines the rate of synthesis of a particular enzyme. A vivid example is the appearance in the cell of inducible enzymes in response to the arrival of the corresponding substrate. Lastly, there is hormonal regulation. A number of hormones are capable of activating or inhibiting many metabolic pathway enzymes.
The example that can demonstrate relationship between metabolism and homeostasis is the process of fat deposition and its mobilization from fat stores with subsequent use in tissues that occurs due to the principle of self-regulation. Increased blood glucose reduces the disintegration of triglycerides and activates their synthesis. On the contrary, when the concentration of glucose in the blood decreases, the splitting of fats intensifies, and non-esterified fatty acids enter the bloodstream (Lanham-New, MacDonald, & Roche, 2011). Synthesis or mobilization cycle in the fat stores of the body is coordinated by the physiological state of organism and nature of the feeding, and regulated by the neuroendocrine system.
Improvement of Metabolic Systems
To improve human body, metabolism modifications could be used to increase resistance to outside factors and prevent diseases. Metabolism is involved in proper functioning of every cell and organ in human body. In broad sense, metabolism and homeostasis are important for such processes as aging, physiological adaptations, and flexibility in disease. Another vector of research may be improving thermoregulation and energetic efficiency of human body.
One of the changes to metabolic system could be inducing autophagy depending on special markers. Recently, Nobel Prize has been awarded for proof that aging and autophagy are interconnected. Modification of ULK1 gene translation system would impact the number and physiological features of autophagosomes (Rabinowitz & White, 2010). The cells could have receptors that would response to ligands connected with “unwanted” cells, such as cancer cells or benign tumor cells that would be recycled, and proteins and lipids could be reused for new cells. It would be another case of selective autophagy, as instead of routine physiological cleavage of old cells it could be active and targeted at tumor cells. However, there must be balance with energy supply as transforming old cells organism needs reserves to build new ones.
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Second, human metabolism has relations to longevity. Several factors proved in experimental conditions have direct impact on the lifespan. For example, metabolic modification could be mTOR signaling. Inhibiting the signaling pathway would increase life of cells as mTOR acts as energy sensor and interacts with mitochondria (Finkel, 2015). Proteins from sirtuin family are regulated by nutrients and they impact acetylation in metabolism of carbons and energy chain. Experiments with sirtuin activation showed increasing life span as well. Thus, how body uses nutrients impacts activity of metabolic pathways and it is tightly interconnected with longevity.
To increase energetic efficiency, it is possible to change either mitochondria or other systems related to thermoregulation. The example is brown fatty tissue. It is present in newborns, rich in mitochondria, very energy efficient, but disappears with time. However, it may be possible to modify existing white adipose tissue and induce browning. This can be made by inhibiting Notch-signalling (Bi et al., 2014). This modification would improve energy balance, thermoregulation, and lipid metabolism in humans.
Another modification could be made in human genome (transcription matrices) to be able to produce essential amino acids. There are nine essential amino acids that cannot be synthesized in humans, and they must come from outside. This modification would help to avoid deficiencies that result in affecting nervous and immune systems, kidney functioning, and increasing risks of systemic diseases. It would be possible as many new proteins are synthesized because of RNA editing and exon and intron genome organization. However, this would not be essential as basic amino acids are easily accessible with food. Thus, there are many ways where metabolism could be improved. The reason is the huge number of processes, enzymes, chemicals, and other factors involved in metabolism processes. The improvement depends on the purpose of the person, however, better energy balance and longevity is beneficial in all cases.
In sum, metabolism is a set of chemical reactions in the body that provide it with substances and energy necessary for life. In metabolism, two main stages can be distinguished: preparatory, when the substance received by alimentary treatment is subjected to chemical transformations, as a result of which it can enter the blood and further penetrate into the cells, and the actual metabolism, represented by chemical transformations of compounds penetrating into cells. Living organisms are thermodynamically unstable systems. For their formation and functioning, it is necessary to continuously supply energy in a form suitable for multifaceted use. Metabolism provides proper functioning of all metabolic pathways and lipids, carbons, proteins, water, micro elements, and vitamins. It is required for homeostasis. Interestingly, metabolism impacts longevity, body resistance to diseases, and body self-regulation. The process can be improved by modifying metabolic functions or genes that are responsible for metabolic pathways. Thus, the most important changes could be made to transform white adipose tissue into brown one to improve thermoregulation and energy resources, supply essential amino acids by self-synthesis, and increase life span by changing genome to impact proper chemical substances in metabolism.