2. Inorganic Substances in Cells

Content of the subchapter:

1. Composition of the live matter
2. Inorganic ions in cells

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Composition of the live matter

At first glance, differentiating between live and dead matter is easy. Nevertheless, the intuitively simple term „alive“ is not defined, and the definition of systems and structures can be similarly ambiguous. Live matters is characterized by a high degree of internal organization, which does not exists for its own purpose, but enables live systems to autonomously regulate and adapt to changes in external factors. Therefore maintaining life requires a continuous exchange of information, energy and matter with the surrounding environment, and keeping stability of the internal environment within rather narrow parameters, so called homeostasis.  Basic rules of thermodynamics apply also for live matter. From a thermodynamic point of view, live organism is categorized as an open system, i.e. systems covering their energy needs from the surrounding environment, in which the level of disorganization thus increases. The balance with the surrounding environment is transitory, rather dynamic, and far from the static balance in an isolated system. To sustain their existence, organism has to gain, transform and use energy, in particular:

1)Active transport of molecules and ions

2) Mechanical work during muscle contraction and other cell movements

3) Biosynthesis of macromolecules and other substances from precursors

4) Generation of heat (thermogenesis)

Comparing the chemical composition of the human body and the crust of the earth, it is qualitatively conspicious that the live matter does not contain any element, which cannot also be found in non-live nature. If we analyze the representation of the elements from a quantitative perspective, living matter is characterized by a high concentration of light elements. The exception is the low content of silicon and aluminum in the human body, although both are among the most common substances on earth. It became a tradition to classify chemical substances according to their prevalence in live matter. We will stick to this grouping practice in the following text.

H, O, C, N and P are considered the primary biogenic, or macrobiogenic substances and can be found in all organisms in quantities exceeding 1 % of their mass. Additional substances can be found in smaller amount. Such substances are called invariable, and are grouped according to their proportional prevalence as olibiogenous (0.05-1 %) (Ca, Mg, S, Na, K, Fe and Cl) and microbiogenic (Cu, Zn, Co, Mn, I and Mo). The last group of elements (e.g. B, Si, V, Br, Li, Se, Ti, As or Al) are found in significant volumes only in certain types of organisms, referred to as microelements.

An inseparable part of live matter are ions – from cations especially Na+, K+, Ca2+ and Mg2+, and from anions Cland oxygen substances, especially PO43- and CO32-.

The total amount of ions is variable between different live organisms, but the relative representation of the main cations is constant, and its composition is similar to that of seawater. The atomic relations of the main cations are shown in table 1, with their concentration in live cells and their environment.

Table 1: Concentration of main cations in live cells and their environment (mmol.l-1)

Compartment Na+ K+ Ca2+ Mg2+
Intracellular liquid 10 150 10-4 10
Blood plasma 140 4,5 2,4 0,9
Sea water 460 10 10 52

From an evolutionary point of view is evident, that the sea had a fundamental role in the creation of life, especially in the early stages of the evolution.

In the following two tables we can see the absolute mass (in grams) of the main elements in the body of the average, healthy male weighing 70 kg.

1) Content of macrobiogenic elements

Element Oxygen Carbon Hydrogen Nitrogen Calcium Phosphor
Body content, in grams 45 000 g* 12 600 g 7 000 g 2 100 g 1 050 g 700 g

*more than half of the body mass

2)The contents of „metallic“ elements is significantly lower

Element Sodium Potassium Magnesium Iron Zinc Copper Manganese

 

Body content, in grams 140 g 105 g 25 g 4,2 g 2,3 g 0,11 g 0,02 g

Although amount of metallic elements is significantly smaller (representing only some 2 % of the total body mass), the life functions are much more dependent on them than the values indicate. This is due to a number of inorganic elements playing a key role in numerous biochemical processes. We can find them in molecules:

1) Metalloenzymes and enzyme cofactors (ca. 40 % of the known enzymes, especially oxidoreductases (Fe, Cu, Mn, Mo, Ni, V) and hydrolases (e.g. peptidases, phosphatases: Zn, Mg, Ca, Fe))

2) Nonenzymatic metalloproteins (e.g. hemoglobin: Fe)

3) Biominerals (bones, teeth: Ca, Si, …)

4) Vitamins and coenzymes (e.g. vitamin B12: Co)

5) Nucleic acids (e.g. DNA n-(M+)n12: Co);  M = Na, K)

6) Hormones (e.g. thyroid hormones – thyroxine, triiodothyronine: I)

7) Antibiotics (e.g. ionophores: valinomycin/K)

8) Chlorophyll (like a low-molecular-weight natural products: Mg)

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Inorganic ions in cells

Chemical substances in the biological system

Sodium, potassium, magnesium and calcium are important compounds of living systems (sodium being the principal extracellular and potassium the major intracellular monovalent cations). Alkaline and alkaline earth metal cations also participate in the stabilization of cell membrane, enzyme, polynucleotide (DNA, RNA) conformations via electrostatic interactions and little bit osmotic effects. Nucleic acids are polyanions and as such require counterions to neutralize partially or completely the negative charged phosphate groups, so that electrostatic repulsions do not overwhelm other stabilizing effects. This charge neutralization requirement is generally accomplished by cations, it is therefore possible to use Na+, K+, Mg2+ cations for their neutralization.

Calcium (Ca)

Calcium is a key component in the structure of biomineralized tissues of mammals, and Ca2+ ions also serve as a key intracellular messenger, supporting a wide range of biological processes. Examples include bone formation, muscle contraction, blood coagulation, exclusion of neurotransmitters and hormones, or being a co-factor in stabilizing proteins. Some extracellular enzymes bind one or more Ca2+ ions and those thus become an inseparable part of their structure. In very few of them, the Ca2+ ion is bound on or close to an active location, which is related to the maintenance of its catalytic activity (phospholipase A2, α-amylase, nuclease).

Magnesium (Mg)

Magnesium is a fundamental component of the human body with a healthy adult consuming on an average 500 mg daily. Considering the fact that Mg can be found in the chlorophyll molecule, leafy vegetables constitute an ideal source. As described above, the human body contains about 25 g Mg2+ ions, of which 65 % is stored in the bones a the remaining 35 % is widely used as a cohesive factor in the conformation of nucleic acids (RNA) or as an enzyme activator. Magnesium is also helping in stabilizing ribosome. Quite all enzymes cooperating with phosphate cofactors (e.g. ATP) require the presence of Mg2+ for their proper function. A deficit of Mg2+ ions in the organism may cause cramps.

Potassium and sodium (Na and K)

Sodium

Natrium (chemical symbol Na) is Latin name for Sodium, and can be found in the periodic table in the group of alkali metals. In the earth’s crust and hydrosphere we can find sodium almost everywhere. Sodium chloride (stone salt – NaCl) as well as sodium nitrate (Chilean saltpeter – NaNO3) are part of soil and water. Seawater contains ~3 % NaCl. The content of Sodium in the human body is around 70-100 g and about 50 % o fit is extracellular, about 40 % in the bones and about 10 % in the intracellular fluids. Sodium is here present in a completely dissociated form as a sodium ion – Na+. The concentration of Sodium (natremie) in extracellular liquids is around 140 mmol.l-1, in intracellular liquids around 3-10 mmol.l-1 and in erythrocytes ~15 mmol.l-1.

The regulation of the level of sodium cations is inherently connected to the metabolism of water. The system of renin-angiotensin-aldosterone is contributing to the regulation of natremia and by extension osmotic and volume homeostasis.

The concentration of sodium ion in the organism is strictly monitored and connected with the osmotic pressure of extracellular fluids. If the absorption of sodium from food increase, the reabsorption of water by kidneys and also excretions of sodium will increase. This is applied vice versa – with receiving a bigger amount of hypo-osmotic fluid, kidneys increased reabsorption of sodium and minimizing the absorption of water. Management of free water provides antidiuretic hormone (ADH, vasopressin), which is released by the hypothalamus neurosecretory cells. Natremie is maintained within the physiological range by aldosterone synthesized by cells of the adrenal cortex. Increased production of aldosterone is mediated by the action of angiotensin, which itself shows a vasoconstrictive effect.

The main function of sodium (with potassium and chlorides) is to maintain a constant osmotic pressure inside / outside of cells and acid-base balance in organism. Sodium with chloride and bicarbonate anions creates base electrolyte, where all cells vital signs take place. Sodium e.g. affects the amount of fluid or maintains the resting membrane potential. Sodium cation is pumped by Na+/K+-ATPase (i.e. Sodium-potassium pump) – sodium is pumped out of the cell, and into the cell is conversely blown potassium. Continuous exchange of ions against their concentration gradients is very energetically demanding – energy need is supplied by ATP.

Potassium (K)

Potassium, in Latin kalium with a chemical symbol K, belongs in the periodic table of elements in the same group of elements such as sodium, i.e. the group of alkali metals. Potassium as sodium could be found in rocks, minerals and in dissolved forms in water.

Potassium is in the organism the main intracellular monovalent cation, unlike its predecessor sodium, 98 % of total amounts in body content are stored intracellularly and only 2 % are located extracellularly. From the total amounts of the intracellular fluid is ca. 86 % localized in muscle cells, ~6 % in liver and red blood cells. The intracellular fluid is possible distinguish free and bound potassium. Bound potassium ion is part of intracellular phosphates and proteins. The ratio of potassium bound/free depend on the pH of the environment. During catabolic processes leads to the release of potassium ions and its amounts in the plasma increases. In the processes that lead to anabolism, by contrast, potassium ions are bonded and their content in the blood plasma decreases.

Potassium ions activated some enzymes – e.g. enzymes of glycolysis or respiratory chain. Potassium cations influence the activity of muscles (especially heart), involved in the utilization of carbohydrates, protein synthesis, during the formation of glycogen and maintain the stability of intracellular fluid.

Cobalt (Co)

Cobalt is an essential element and only a little over 1 mg Co is present in an adult human, with the largest amounts being in liver, skeletal muscles, bone, hair, adipose tissue and blood. As essential part of vitamin B12, is important during creation of red blood cells.

Zinc (Zn)

An adult has about 1.5-3.0 g zinc with the largest amounts being in liver and bone with the smallest amounts in muscles. There is evidence that Zn concentrations in blood and several tissues vary considerably in response to many stimuli. Zinc appears to be critical in many functions; especially there are a number of enzymes (about 300) which, at their activity required the presence of zinc (such as alcohol dehydrogenase, carbonic anhydrase, or lactate dehydrogenase). However, it participates in many enzymatic functions – it has antioxidant properties, as part of the transcription factors involved in the synthesis of DNA (important in cell proliferation, tissues regeneration and wound healing) or is applied in the metabolism of carbohydrates. In the fact zinc is forming complexes with insulin molecule.

Molybdenum (Mo)

The trace element molybdenum is essential for nearly all organisms and forms the catalytic centre of a large variety of enzymes (metalloenzymes) such as xanthine oxidases (an important role in the metabolism of purines), aldehyde oxidase and sulphite oxidase.

Xanthine oxidase is an enzyme belongs to the family of oxidoreductases, which with the help of a co-factor FAD and iron-molybdenum complex, catalyzes the following chemical reaction:

Xanthine + H2O + O2 → urate + H2O2

Molybdenum plays an important role in the metabolism of purines – in the final phase of conversion xanthine to uric acid. Furthermore, molybdenum applied in the release of iron from ferritin in the intestinal mucosa and in mediating the release of iron from ferritin from liver and in erythropoietic tissue or placenta. Molybdenum-flavin enzymes are also involved in the respiratory chain.

Aldehyde oxidase is a complex molybdo-flavoprotein that belongs to a family of structurally related molybdenum-containing enzymes (its cofactor is flavohemoprotein and molybdenum), oxidoreductases and catalyzes the following chemical reaction:

Aldehyde + H2O + O2 → carboxylic acid + H2O2

Sulfite oxidase is a molybdo-heme enzyme that is important in sulfur metabolism catalyzing a final step in oxidation in sulphur molecule in right amino acid (cysteine) on inorganic sulphate, respectively catalyzes the oxidation of sulphite to sulphate.

Beside role of enzyme cofactor, molybdenum together with fluorine increase strength of bones and teeth and contribute to prevention of tooth decay.

Manganese (Mn)

Normal adult human has about 10-20 mg Mn, highest concentrations are found in liver, pancreas and kidney. The main function of manganese is to facilitate the deposition of calcium and phosphorus in bones, which is designed to prevent e.g. against osteoporosis. It applies even in the synthesis of thyroid hormone or sexual hormone.

Chromium (Cr)

Normal adult human has about 6 mg chromium. There are exits two chromium forms- trivalent and hexavalent. Trivalent Cr shows positive biological effects in the upper gastrointestinal tract, but only in very small amounts (hexavalent Cr is better absorbed, but only trivalent Cr is biologically active as an essential element). Hexavalent chromium is toxic for human body and his exposition can play role in pathogenesis of development tumor and skin disease. Role of trivalent chromium consist of metabolism of saccharides, when some studies indicates his positive influence to insulin function. On the other hand different studies didn´t confirmed this influence, so chromium is not commonly used in clinical practice.

Copper (Cu)

The average-weight human body contains about 100-110 mg of copper, highest content is located in liver cells, central nervous system, kidneys and heart. The essentiality of Cu is the consequence of its role in metalloenzymes involving several critical biochemical pathways. Several of these enzymes are noted under: Superoxide dismutase, which metabolize the potentially damaging superoxide anion. Lysyl oxidase is a monoamine oxidase required for cross-linking collagen and elastin, the structural macromolecules of connective tissue. Dopamine β-hydroxylase, amine oxidase and tyrosinase are all Cu containing enzymes that interconvert the major neurotransmitters dopamine, noradrenaline and adrenaline, probable accounting for the high concentration of Cu in the brain. The latter enzyme, tyrosinase, is also a key step in pigment production. Ferroxidase (better known as ceruloplasmin before its role in mobilizing and oxidizing Fe from storage sites was recognized) is believed to account for 95 % of serum Cu, and appears to be a multifunctional protein serving as a major transport system for Cu as well. Copper is widely distributed by liver to the others tissues and the its excretion from the body.

Iron (Fe)

The average-weight human body contains approximately 4-5 g of iron. From this amount, about 60-70 % is present in hemoglobin in red blood cells, 15 % is bound to the iron storage protein ferritin, ~3-5 % is localized in muscle myoglobin, approximately 0.2 % occurs as a component of enzymes in respiratory chain and 0.004 % is bound to the serum transport protein transferrin. Iron allows transport of oxygen in the blood, is essential for many enzymes and is involved in production of energy. It´s important for a number of vital functions: supports the growth, reproduction, wound healing and immune system. The complete absorption of iron requires copper, manganese and vitamin C.

Subchapter Author: Vašek Pavlíček

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