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Chapter 3.

Molecular Bases of Chemical Organization of the Cell

3.1 Chemical Elements in Living Organisms

Living matter is made up of more than 60 chemical elements, mainly light ones. Heavy
elements are not proper for life because they are chemically inert and unsolvable in water. The
chemical elements can be grouped into: macroelements, microelements and oligoelements.
1) Macroelements (major chemical elements in amount of 2-60% each) are core of the cell
structures. They are: C, H, O, N.
The main element of organic compounds, carbon has unique features. It is a tetravalent
element whose valence lines are pointed towards the tips of a regular tetrahedron. Carbon can
establish simple double or triple bonds with other atoms (H, N, O), forming long linear, ramified
or cyclic chains. This results in an enormous variety of macromolecules. The ability of carbon to
make double or triple bonds with other elements also leads to unsaturated, highly reactive
compounds of vital importance in metabolic processes of the organisms.
2) Microelements (less abundant elements, about 0.02-0.1 % each) are: P, S, Cl (metaloid
elements), and Na, K, Ca, Mg (metals) respectively. Among these, Na is more abundant
outside the cell, while K is more abundant inside the cell.
The first 2 groups of elements constitute the so-called plastic elements (of which all
biological structures are made up).
3) Oligoelements (trace elements, less than 0.02% each) are very important for life and medicine.
There are dozens of such elements. Some are part of protein structures, as is the case of Fe
in hemoglobin and myoglobin, with role to bind and transport oxygen. Iodine (I) is part of
thyroid hormones. Co, Zn, Lead (Pb) or Cd are enzymatic activators/inhibitors, influence
cardiovascular system, formation of gametes, intra-uterine evolution of embryo and foetus, or
induce neuropsychological conditions in children. Thus, in areas polluted with Pb or Cd
compounds there is a higher incidence of mentally retarded children.
Absence of oligoelements from water or soil can induce endemic diseases in those
geographical areas biochemical endemics: lack of iodine in the water and soil results in
hyperthyroidism in adults and a type of cretinism in children; Fe insufficiency produces feriprive
anemia; lack (or insufficiency) of Se is associated with a higher risk of cancer (i.e. in Northern
Europe); lack of F in water leads to dental caries (compensated by toothpaste usage); Mg
deficiency in water is associated with a higher incidence of cardiovascular diseases.

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3.2 Chemical substances

Relative ratio of chemical substances is constant in all living beings. For example, both human
body, in all its complexity, and an Escherichia coli (E. coli) cell contain about 70% water, 15%
proteins, 7% nucleic acids, 3% glucides and their metabolites, 2% lipids and their
metabolites, 1% inorganic ions and several other compounds (under 1%). This is an illustrative
aspect of material unity of biosphere. However, at cellular level, differences between cells are
found, even in the same body (consider neurons as compared to red blood cells, muscle or
epithelial cells).

3.2.1 Inorganic substances


3.2.1.1 Water

Water is the essence of life, a primordial and most abundant molecule in all living cells. In a
human body of 70 kg, water weights about 40 kg!
In organism, water is present in 2 compartments: intracellular water (about 55%) and
extracellular water (about 45%), found in plasma, lymph, interstitial liquids (that fill the empty
spaces between the cells), digestive secretions, cephalorachidian liquid or liquids in serous
cavities (pleura, peritoneum).
Within the cell, water is the main constituent of each and every cell. Younger cells (higher
metabolic activity) have a higher content of water (up to 95%) compared with older ones (about
60%). Sometimes, the water molecules represent up to 99% of the total number of molecules in a
cell!
Water is the only solvent of the living matter, in which all the other compounds are diluted
or suspended. Chemistry of life consists of chemical reactions occurring in aquatic solutions.
Physico-chemical properties of water explain why life cannot exist without water:
1) Arrangement of oxygen and hydrogen atoms produces electric dipole of the water molecule,
with the negative (anionic) pole at oxygen and the positive (cationic) one at hydrogen atoms. In
fact, the electrical charges are oriented towards the tips of a regular tetrahedron whose centre is
occupied by the oxygen atom, while the hydrogen atoms occupy two of the apexes.
The polar nature of water confers it a high dielectric constant (80 times higher than of
vacuum). This leads to a marked attenuation effect of electrical interactions in water and
consequently to defence of living structures against intense electrical fields (electrical shield).

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The same polar nature makes the water a very good solvent for majority of substances with
ionic bonds (which dissociate in water), as well as for polar substances with covalent bonds.
2) Water molecules disassociate in protons and hydroxyl ions; a proton can attach to another
water molecule resulting in a hydronium ion:

H2O H+ + OH-; H+ + H2O H3O+ As a result: 2H2O H3O+ + OH-

In this form water participates in chemical reactions within living organisms.


3. Hydrogen bonding: one water molecule can bind 1 to 4 water molecules by hydrogen bonds.
Depending on the aggregation state these bonds are stable (in the crystalline structure of ice) or
labile (in liquid water dynamic molecular packages are continuously formed and broken). These
bonds confer water a high caloric capacity, being an excellent cooler. Water absorbs a lot of
energy for the breaking of hydrogen bonds, thus protecting the living structures from caloric
energy (heat) released in different biochemical processes (is a thermal shield). On another hand,
the hydrogen bonds confer water a high value of vaporization heat, important for cooling of the
living organisms by water evaporation (thermoregulatory property).
The aquatic phase consists of the so-called free water (95%), representing a solvent or
dispersion medium for organic and inorganic substances, and the bound water (5%), which
consists of water molecules bound by hydrogen bonds to other structures (mainly proteins).
Besides the aquatic phase, a non-aquatic phase is found in the living cells. Such areas where the
water is excluded are the inner space of macromolecules (proteins or nucleic acids) or inside cell
membranes.
Transport of water through membranes in all cells, from bacteria to humans, is
accomplished by specialised proteins called water-channel proteins or aquaporins (from latin
aqua=water, porus=passage). The first water-channel protein, later called aquaporin 1 (AQP1),
was discovered in the human red blood cells membranes by a team led by Prof. Gheorghe Benga
(Dept. of Cell and Molecular Biology, I. Haieganu University of Medicine and Pharmacy,
Cluj-Napoca), in 1985. For the discovery of the water-channel proteins the US scientist Peter
Agre, who redescovered AQ1 several years later, was awarded the 2003 Nobel Prize for
Chemistry.
Aquaporins were found in bacteria, in plants (over 200 various types), as well as in
animals. In humans 11 types have already been described, among those AQ1 in the red blood cell
membrane, in epithelial cells of the proximal contorted tubes (role in the concentration of urine),
in endothelium of the capillary vessels and in choroid plexi. AQP2 is found in the renal collecting

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tubes, having role in the concentration of urine, together with the antidiuretic hormone (ADH).
AQP3 is located in the renal collecting tubes, in lungs and brain, and AQP0 in the crystalline
(keeps its transparency). Thus, aquaporins are responsible for regulating all processes of
quick water transport in organisms. Numerous implications of the aquaporins in pathology
(diabetes insipidus, edematous cardiac insufficiency, diseases of the nervous system etc.) were
described.

3.2.1.2 Mineral salts

Mineral salts can be found as ions, or combinations bound to proteins, nucleic acids, etc.
Among the cations, Na+ (the main extracellular cation), K+ (the main intracellular cation),
Ca2+, Mg2+ could be mentioned, while among anions are phosphates (PO43-, HPO42-, H2PO4-),
sulphate (SO42-), carbonates (HCO3-, CO32-) and nitrate (NO3-).
The presence of ions in organisms is of great importance, as they influence enzymes
activity and various other cellular processes such as permeability, excitability, conductibility,
contractility, citoplasmic viscosity or cellular divisibility. Also, the ions participate to the osmotic
pressure and the acido-basic equilibrum (intra- and extra-cellular pH), being vital for living
organisms. Small variations of certain ions concentration in plasma or at cellular level can
sometimes result in major functional alterations (such as cardiac arrhythmias) or even sudden
death.
The ionic concentration is relatively constant in all the living bodies (about 1% of total
weight). This is another evidence of the material unity of the biosphere.

3.2.2 Organic substances


3.2.2.1 Glucids

Glucids (sugars) can have either a plastic or an energetic role in the cells. Certain
monosaccharides, such as ribose or deoxyribose, have a plastic role as they are present in
the structure of nucleic acids. On the other hand, glucose is the main monosaccharide used as
cellular fuel; it has mainly an energetic role. The glucose molecule is particularly suited for
such a role. Being highly soluble in water, it is easily absorbed from the digestive tube and
transported by the blood flow into the whole organism. Also, as the glucose molecule is
extremely stable (it is a hexose, more stable than a pentose or a heptose). When the covalent
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bonds are broken, an extremely high energy is released that provides important energetic
resources. Finally, glucose is easily metabolised (via glycolysis and other metabolic pathways),
thus producing the energy used for the synthesis of ATP (adenosine triphosphate).
A representative of polysaccharides is glycogen as the main storage form of glucose in
human and animal organisms (in plants, this role is accomplished by starch). Glycogen is made of
glucose residues bonded via 1-4 glycosidic bonds that form long chains and via 1-6 glycosidic
bonds that form ramifications. Several aspects of the glycogen structure-function relationship
are noteworthy:
a glycogen molecule stores several thousands of glucose molecules, thus osmotic pressure in
the cell being reduced to a minimal level (the osmotic pressure depends on the number of
particles, not on their size);
enzymes that attach or separate glucose molecules to/from glycogen may work
simultaneously on many ramifications, thus the glycogenesis (the formation of glycogen
from glucose molecules), and the glycogenolysis (the release of glucose molecules form
glycogen) are very quick metabolic processes. In the human body, glycogen is present in high
amounts in liver and muscles cells. After meals (especially if rich in sugars), as the glucose is
absorbed in blood, hyperglycemia occurs; however, the glucose is quickly stored in liver and
muscles, glycemia thus falling back to normal ranges. On the other hand, between meals and
particularly during periods of intense physical efforts, the organism comes to a state of
hypoglycemia; this is rapidly counterbalanced by the release of glucose molecules from the
hepatic glycogen for energetic purposes.
If the rapidly restored hepatic glycogen is currently used for glucose release, the muscular
glycogen (which, once consumed, is restored over a longer period) is used only after the hepatic
glycogen is consumed: in inanition, extreme physical efforts (such as marathon running,
mountain climbing or professional boxing).
Although the nervous system doesnt have a glycogen storage system, it is a big consumer
of glucose (the main fuel for neurons), being highly sensitive to hypoglycemia.
The liver glycogen can be studied with the light microscope using special colorations (i.e.
with Bests Carmine), red glycogen granules being visible, while at the electronic microscope one
can observe it as black granules in the cytoplasm.
Mucopolysaccharides are polysaccharides in which the monomer units contain amino
derivatives of monosaccharides (glucoseamine, galactoseamine etc.), forming long chains and
resulting in very big fibrous molecules. Mucopolysaccharides can attach to lower-size
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polypeptidic chains, forming the so called proteoglicans. These are important components
especially for the extracellular matrix, the fundamental substance of the conjunctive tissue.
Examples of mucopolysaccharides are hyalouric acid, codroitin-sulphuric acid, keratan-sulphate,
dermatan-sulphate or heparine.
Observation of mucopolysaccharides is possible after their staining in specific
histochemical reactions. Because they are highly hydrated (gels with high viscosity), the
mucopolysaccharides accomplish mainly mechanical functions in the conjunctive tissue (support,
shock absorption, lubrication), but they also actively participate in the tissue metabolism.

3.2.2.2 Lipids

Lipids (fats) have various roles in the cell:


- plastic role: they participate to the structure of cell membranes;
- energetic role: they constitute the fuel with the highest energetic value (lipids provide
more energy than equivalent quantities of glucides or proteins);
- regulatory role: accomplished by several hormones (e.g. steroid ones) and vitamins of
lipidic nature, as well as prostaglandins.

a. Simple lipids, used for energy gain via oxidative processes or for the synthesis of other types
of lipids, are called free fatty acids. The free fatty acids with chains of 16 and 18 carbon
atoms are used by the cells. Those with less than 14 C12 atoms are detergents that destroy the
cellular membranes, while those with more than 20 C12 atoms are highly insoluble and thus
useless in metabolic reactions.

b. Triglycerides (also called neutral fats) are the storage form of lipids in specialised cells with
depositing function (i.e. adipose cells or adipocytes). In such cells the nucleus is pushed
towards periphery and the cytoplasm is occupied by a large lipidic vacuole. In pathological
conditions, triglycerides can also be found in the cytosol of other cells, for example in cases
of hepatic steatosis in obese and alcoholic patients, or in patients with hepatic diseases or
presenting intoxications due to organic solvents. Lipids present in cytosol are observed using
specific staining methods: with Sudan Black they turn to black, while with Sudan III they
are stained in orange.

c. Complex lipids are present in the cellular membranes as phospholipids or glycolipids.

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Some phospholipids (glycerin-phosphatides) are based on the glycerol molecule, where
two carbon atoms have esters of 16-18 C12 fatty acids (with up to 6 double covalent bonds in case
of the unsaturated ones), while to the third carbon atom a polar group with a phosphoric acid
radical and various other substances are attached. Pending on the polar group, they may be
phosphatidylcholine (lecitin), phosphatidylethanolamine, phosphatidylserine or
phosphatidylinositol. Another important phospholipid is sphingomyelin, in which sphingosine
(an amino-alcohol) is esterified with a fatty acid, while the polar group is phosphorylcholine (the
same as in phosphatidylcholine).
Glycolipids are also based on sphingosine, on which a fatty acid is bound, but the polar
groups consist of one or several glucidic radicals (in cerebrosides or gangliosides
respectively).
Phospholipids and glycolipids rearrange in water forming the so called micelles" or
lipidic bilayers. This is possible due to the hydrophobic property of the fatty acid chains (with the
hydrophobic groups orientated towards the inside of the micelle or bilayer) and the hydrophylic
property of the polar groups. Such molecules are called amphiphiles. The phospholipids bilayer
represents the basis of biological membranes structure.

3.2.2.3 Proteins

Proteins have numerous and various important roles at cellular level:


- plastic role: they are part of all cellular structures, including membranes;
- participate in chromatin structure;
- role in transport and storage of various substances (Fe in the liver, O2 to the cells etc.)
- role in muscle contractions and all other cell movements;
- resistance and elasticity of different tissues;
- regulatory roles (in cell growth, development and multiplication control of cellular
division);
- catalytic role: almost all enzymes (with clearly defined roles in all metabolic processes)
are proteins;
- role in immune defensive reactions of the organisms;
- receptor role (synaptic receptor etc.)
- role in nutrition (e.g. ovalbumine)
- role in maintaining osmotic pressure and pH at constant levels.
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Accomplishing such various roles is explainable if we consider the structural diversity of
proteins on one hand, their specificity on the other.
Proteins are macromolecules formed by polycondensation of amino-acids by peptide
bonds (-CO-NH-), resulting in chains of a great variety of length, from very short to very long
(thousands of amino-acids). Chemically, proteins display a great diversity of structures and
functions as well.
20 different amino-acids compose the proteins. Their heterogeneity in size (from small
to highly voluminous amino-acids) and polarity (hydrophilic polar, or neutral) is reflected upon
the heterogeneity of proteins. Amino-acid availability for a large variety of combinations results
in an enormous number of possible sequences. The amino-acid sequence in the proteins (primary
structure) largely determines the spatial arrangement of the polypeptide chain (secondary = bi-
dimensional and tertiary = spatial structures) so that the most thermodynamically stable
conformation is always adopted. The tri-dimensional (spatial) structure, which is specific for each
family of proteins is essential for their biological activity. Various sequences correspond to
extremely various spatial structures and, consequently, functions. Moreover, some proteins have
in their structures lipidic radicals (lipoproteins), glucidic radicals (glycoproteins), phosphoric
groups (phosphoproteins), sulphur (sulphur proteins), metals (metaloproteins) etc. Protein
heterogeneity also resides in the association of several polypeptidic chains in a single functional
protein (i.e. the hemoglobin consists of 4 polypeptide chains).
Protein specificity implies their propriety of specifically combining with particular
substances, even if those substances are present in very small concentrations in the environment.
Specific bondage is a consequence of the structure-function relationship underlying several types
of molecular interactions in the living world: antigen-antibody reactions, enzyme-substrate or
receptor-ligand reactions.
Proteins can be studied with the light and electronic microscopes in various ways:
a) amino- or sulphidryl- groups in the polypeptide chains can be observed after cytochemical
reactions resulting in coloured precipitates (visible in the light microscope) or electron-dense
precipitates (visible in electron microscope);
b) enzymatic reactions (for enzymes) on tissue sections lead to stained precipitates;
c) specific antibodies targeted against the respective protein can be used: antibodies marked
with fluorescent groups can be seen with light microscopes (in UV), while the electron
microscope allows identification of electron-dense metals such as gold or iron, via antibodies
marked with colloidal gold or ferritin (a protein rich in Fe atoms).
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3.2.2.4 Nucleic acids

Nucleic acids are macromolecules formed by nucleotide polycondensation. A nucleotide consists


of the following components:
- a nitrogenous base, purine (adenine, guanine) or pyrimidine (thimine, cytosine, uracil);
- a pentose, either ribose (in RNA) or deoxyribose (in DNA);
- a phosphoric ester (radical)
In the molecule of any nucleic acid four nitrogenous bases (two purines and two
pyrimidines) can be found that constitute four different types of nucleotides: ribonucleotides (in
RNA) and deoxyribonucleotides (in DNA). The sequences generated by the nitrogenous bases or
the nucleotides in the nucleic acids are very diversified: not as the sequences generated by the 20
amino-acids, but diversified enough to secure biological role of the nucleic acids. The nucleic
acids are heredity molecules; they represent genetic material, storage system of genetic
information.
Heredity is the particular feature of the living organisms to give offspring similar to the
parents, in certain (environmental) conditions. It involves transferring hereditary characteristics.
The genetic material is contained in genes, formed out of hundreds to thousands of nucleotides
that determine all biochemical, morphological, behavioural and other characteristics of an
organism. Heredity implies stability. The DNA macromolecule has a double-helix (duplex)
universal structure in which two polynucleotide chains are whirled (forming a huge spiral). In the
case of RNA, universal types of spatial structures are seen in the tRNA (transfer RNA), mRNA
(messenger RNA) or rRNA (ribosomal RNA). Due to their structure, the nucleic acids are fit for
their biological role: to confer interspecific and intraspecific (individual) variability, each
individual being unique genetically speaking (with the exception of monozygotic twins, where
in similar material changes are generated by environmental factors).
Location of the nucleic acids within the cell:
- DNA is located in nucleus, mainly in chromosomes (chromosome DNA constitutes major
part of the genetic material in the eukaryote cell), in nucleolus (small amount of nucleolo-
associated DNA), and in cytoplasm (in mitochondria, forming mitochondrial genes). In
plants, DNA is located in cytoplasm, mitochondria and chloroplasts.
- RNA is located within the nucleus (in nucleolus) and in cytoplasm: rRNA is located in
ribosomes, while tRNA and mRNA are found in the soluble phase of the cytoplasm.

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Nucleic acids within the cell can be observed by specific cytochemical reactions with
methyl green and pyronine (combined): methyl green gives DNA a green-blue colour, while
pyronine turns RNA to pink. Generally speaking, the cells are visualised with a green-blue
nucleus (DNA excess), pink nucleolus and cytoplasm (due to the large amount of rRNA).

3.3 Biochemical organisational unity of the (living) cell

There are several unitary principles concerning the chemical and biological organisation of the
living cell:
a) Cells are composed of identical chemical elements and substances, in similar percentages;
b) Ionic composition of the body fluids is constant in various animal species;
c) Biochemical processes in biosphere follow a unitary scheme: the main metabolic processes
in the cell (such as glycolysis, citric cycle, fatty acids oxydation, biosynthesis of fatty acids
and phospholipids) follow the same stages, catalyzed by similar enzymes.
d) Some molecules are universally distributed within living cells: D-glucose, fatty acids with
16 to 18 C12, the 20 amino-acids, sterols, purine and pyrimidine basis are found in every
cell. Also, co-factors such as NAD, NADP, CoA, coenzyme Q or vitamins are
omnipresent.
e) ATP is the prototype of the macroergic molecules, the universal currency in energetic
exchanges at cellular level. There are three basic systems for ATP generation identical in
all cells: glycolysis, oxidative phosphorylation in mitochondria (oxidative process coupled
with ATP synthesis) and photosynthesis. Evidently, the latter is specific for plants.
f) DNA replication and protein biosynthesis also follow the same mechanisms in all living
cells.
g) Control mechanisms for all cellular processes are also common for the whole biosphere.

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