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E BOOK Biochemical and Molecular Pharmacology in Drug Discovery Drug Discovery Update 1st Edition by Mithun Rudrapal PhD , Chukwuebuka Egbuna PhD , William Chi Shing Cho

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C H A P T E R
1
Structures and functions of
biomolecules
1. Introduction
1.1 About biomolecules
The biomolecule is a general term representing the molecules present in the organisms
which are necessary to one or the other biological processes like cell growth, cell division,
cell proliferation, development etc. These biomolecules are the major elements of living organisms, which are often endogenous, produced within the organisms. But there is also a
need for exogenous biomolecules, for instance nutrients, for the survival.
The word Biomolecule is originated from two words i.e. “Bio” (Bios, from ancient Greek)
which means life and “Molecule” (molecula, from Latin) means two or more atoms held
together by chemical bonds. The biomolecules are the building blocks of the life and can
be defined as the molecules produced by the cells of the living organisms [1]. Most of the biomolecules are organic in nature, as Carbon, hydrogen, Oxygen and nitrogen are the four major elemental composition, which make up about 96% of the body’s mass. There are majorly
four types of biomolecules namely, carbohydrates, proteins, nucleic acids, and lipids [2]. For
their biological role in a functioning cell or organism, biomolecules interact with each other or
rather small molecules in their environment. Drugs can exploit interaction with biomolecules
to manipulate their biological function to obtain a therapeutic effect. Structure determination
3
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1. Structures and functions of biomolecules
of biomolecules that (could) serve as therapeutic target is an important starting point in
rational drug design.
1.2 Carbohydrates
The carbohydrates are the sugar molecules called saccharides, they are made up of atoms
of Carbon, Hydrogen and Oxygen in the ratio of 1:2:1. The general formula of carbohydrates
is (CH2O) n. They can also be referred as “hydrated carbon.” The bond which joins one unit of
saccharide with other is called glycosidic bond [3]. Carbohydrates serving as therapeutic targets such as glycans attached to proteins, known as glycoproteins, are involved in various
infectious diseases. Targeting these glycans can lead to novel therapies. Certain antiviral
drugs, such as oseltamivir (Tamiflu), inhibit viral neuraminidase enzyme by binding to their
carbohydrate components. Carbohydrates in vaccine development like the pneumococcal
conjugate vaccine use carbohydrate-based antigens to induce immunity against bacterial infections [4]. The structures of carbohydrates has been discussed in the next section. The summary of its classification has been summarized in Fig. 1.1.
1.2.1 Structure of carbohydrates
Name of structure
No. of saccharide units
Examples
Monosaccharides
1
Glucose, galactose, fructose
Disaccharides
2
Sucrose, maltose, lactose
Oligosaccharides
2e10
Raffinose, stachyose, heparin
More than 10
More than 10
Starch, cellulose, glycogen
Hyaluronic acid, chondroitin sulfate, keratin sulfate
Polysaccharides
a) Homopolysaccharides
b) Heteropolysaccharides
FIG. 1.1
The constituents of carbohydrates and their brief structural depiction.
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1. Introduction
5
*Structures of some of the carbohydrates*
Glucose (C6H12O6): Abundant monosaccharide in the body
Maltose (C12H22O11): C1 of a glucose þ C4 of a glucose[a-1,4-glycosidic linkage]
Sucrose(C12H22O11): C1 of a glucose þ C2 of b fructose [a-1,b-2-glycosidic linkage]
Lactose(C12H22O11): C1 of b galactose þ C4 of b glucose[b-1,4-glycosidic bond]
Continued
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1. Structures and functions of biomolecules
Raffinose: (C1 of a galactose þ C6 of a glucose) þ (C1 of a glucose þ C2 of a fructose) [a-1,6 and a-1,
b-2 glycosidic linkage]
Cellulose: C1 of b glucose þ C4 of b glucose [b-1,4 glycosidic linkage]
1.2.2 Functions of carbohydrates
U Carbohydrates serves as energy source to the body yielding an average energy of
4 kcal/g.
U Glucose is the major energy source for Central Nervous system.
U Carbohydrates are required for the contraction of muscles.
U Carbohydrates are involved in the management of blood glucose level and insulin
metabolism.
U Carbohydrates play a key role in amino acid and fatty acid metabolism.
U Carbohydrates serves as structural components.
U Carbohydrates promote the growth of desirable bacteria in the gut.
U The dietary fiber stimulates the peristaltic movement & maintains the health of digestive
system.
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1. Introduction
Carbohydrates and receptors interaction
On the basis of several papers, the interaction between the carbohydrates and the
receptor is known to be brought about by the
hydrogen bonds between the hydroxyl
groups of carbohydrates and the polar amino
acid residues of the proteinaceous receptors.
Some of the metal ions can also mediate the
interaction by forming the bridge between the
Oxygen atoms of hydroxyl group of carbohydrate and the negatively charged protein
residues. For example, the C-type lectin receptors which acts as pattern recognition receptors as they are capable of recognizing
pathogen associated molecules and stimulates the intracellular signaling pathways to
regulate the immune response. These types of
receptors are primarily expressed by macrophages, monocytes and dendritic cells and
recognize fucose, mannose like carbohydrate
structures [5].
1.3 Proteins
Proteins are the macromolecules composed of specific combinations of amino acid residues which are linked by peptide bond which links between the amine group of one amino
acid and carboxyl group of the adjacent amino acid. Every cell consists of proteins as they
are critical for the life to exist. The properties of proteins must be determined by the amino
acids they contain and the order in which they are linked. While these properties may
become complex and far removed from any property inherent in single amino acids, the
existence of a limited set of fundamental building blocks restricts the ultimate functional
properties of proteins.
1.3.1 Structure of proteins
There are four levels of structures. They are as follows.
Levels of structure
Description of structure
Major bonds involved
Primary structure
Specific sequence of linearly arranged amino
acids [6].
Peptide bond
Secondary structure
The folded patterns of amino acids due to
hydrogen bonding. Alpha helix (polypeptide
chain curved like a spiral) & Beta pleated
sheets (beta strands connected laterally by
hydrogen bonds with the help of loops
forming sheet like structure) [7].
Hydrogen bonds between atoms of
polypeptide backbone (between partially
negative oxygen & partially positive
nitrogen
(Continued)
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1. Structures and functions of biomolecules
dcont’d
Levels of structure
Description of structure
Major bonds involved
Tertiarystructure
3-dimensional structure consisting motifs
(chain like structure made by connected
secondary structured pieces) and domains
(the independent folding unit of a protein
with specific function) caused by side chain
interactions [8].
Hydrogen bonds, disulphide bonds, salt
bridges and hydrophobic interactions
Quaternary structure
Proteins which consist more than one
polypeptide chain.
Hydrogen bonds, ionic bonds, disulphide
linkage, Vander Waals interactions
1.3.2 Functions of proteins
U Protein plays a critical role in maintaining body tissues during its growth, development
and repair mechanisms.
U Proteins are the major structural components. For example, skin consists of collagen.
U Proteins also serve as major source of energy after carbohydrates.
U All enzymes are proteins, which accelerate the speed of the reactions in the body.
U Proteins also acts as transporters, thereby helps in transporting the small molecules,
gases throughout the body. For example, hemoglobin transports oxygen.
U Proteins acts as protective agents like antibodies which protects the body from foreign
invasion.
U Protein helps to store some substances in the body. For example, the ferritin is a protein
found in liver which stores iron.
U Proteins are responsible for the movement. For example, actin and myosin helps in muscle movement.
U Hormones are also the proteins which acts as chemical messengers.
U Plasma proteins helps to maintain acid-base balance and fluid balance in the body.
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1. Introduction
Protein and receptor interaction
As most of the receptors are proteins, it is
the protein-protein interaction. This interaction is the result of establishment of highly
specific physical contact between two or more
protein molecules which involves hydrogen
bonding, electrostatic interactions, hydrophobic interactions etc. For example, Leptin,
is the proteinaceous molecule (a hormone) on
binding to long form (ObR form) of leptin
receptor, it controls the satiety index or food
intake. The major domain responsible for the
interaction is present in the leptin receptor,
which is an intracytoplasmic domain containing 302 amino acid residues that contains
a number of motifs which facilitates the
interaction between leptin and leptin receptor. The mutation of this receptor leads to
obesity [9].
1.4 Lipids
Lipids are a group of organic compounds including fats, oils, waxes, sterols, phospholipids
etc. They are soluble in organic solvents but insoluble in water as it is a polar solvent. Lipids
are hydrophobic in nature [10].The activity of membrane transporters is affected by lipid content, which has an impact on drug absorption and efflux. Transporter localization involves
specialized membrane regions called lipid rafts.
1.4.1 Structure of lipids
Lipids
Structural description
Examples
Fats and oils
Glycerol & three fatty acids
Caproic acid, palmitic
acid
Waxes
Higher straight chain fatty acids & high molecular weight monohydric
alcohols.
Carnauba wax, Bees wax
Sterols
Steroid based alcohol having a hydrocarbon side chain (8e10 carbon
atoms) at 17 beta position and a hydroxyl group at 3 beta position.
Cholesterol, stigmasterol
Phospholipids Glycerol which bridges two nonpolar fatty acid tails & a polar head of
phosphate group.
Phosphatidylcholine,
phosphatidylserine
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1. Structures and functions of biomolecules
*Structures of some lipids*
Caproic acid
Cholesterol
Phosphatidylserine
1.4.2 Functions of lipids
U Lipids play key role in the structure and functions of cell membrane.
U The steroid hormones act as intracellular messengers.
U Lipids act as protective coating in the leaves of plants.
U The lipids present in the subcutaneous membrane under the skin provides insulation
from cold.
U Lipids acts as cushioning substances.
U Lipids are also the constituents of fat-soluble vitamins.
Lipid and receptor interaction
The interaction of lipid molecules with the
receptors is gaining importance in recent years
because there is continuous research is going on
regarding the utilization of the lipids as one of
the therapeutic agents. For example, the interaction between cholesterol and CC motif che-
mokine receptor 3, which is a class of G-protein
coupled receptors consist of cholesterol recognition/Interaction Amino Acid Consensus
motif (CRAC) and a CARC motif in TM1. This
interaction is of importance in case of inflammatory responses, arthritis, asthma etc. [11].
1.5 Nucleic acids
Nucleic acids are the long chain of polymeric molecules made of repeating units called nucleotides, so that can also be referred as polynucleotides [12]. Ribonucleic acid (RNA) and
Deoxyribonucleic acid (DNA) are the two major nucleic acids which acts as carriers of genetic
information from one generation to the next generation [13].
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1. Introduction
11
1.5.1 Structure of nucleic acids
Nucleic acids
Structural components
Ribonucleic acid (RNA)
Single stranded structure consists of ribose sugar, and a phosphate group linked by
phosphodiester bond which forms backbone of the RNA.And also, the four nitrogenous
bases (A, G, U, C)*, these purines & pyrimidines are linked by hydrogen bonds.
Deoxyribonucleic acid
(DNA)
Double stranded structure consists of deoxyribose sugar and a phosphate group linked by
phosphodiester bond which forms backbone of the DNA. And also, the four nitrogenous
bases (A, G, T, C)* are linked by hydrogen bonds similar to RNA.
*A-Adenine, G-Guanine / Purines; C-Cytosine, T-Thymine, U-Uracil / Pyramidines.
1.5.1.1 Types of RNA
There are three major types of RNA
1. mRNA (messenger RNA): It contains the information in the form of codons, which is
copied from DNA for the synthesis of proteins.
2. tRNA (transfer RNA): It contains anticodons which identifies their specific codons on
mRNA thus then carries the specific amino acids to the ribosomes to build proteins.
3. rRNA (ribosomal RNA): The structural component of ribosomes which catalyzes the
protein synthesis process and ensures the correct synthesis of specific protein molecule.
1.5.2 Functions of nucleic acids
U Nucleic acids are the chemical basis of heredity.
U They act as reserve bank of genetic information.
U Nucleic acids are the basic information pathway.
U DNA directs the synthesis of RNA.
U RNA directs the synthesis of proteins.
Nucleic acid and receptor interaction
The nucleic acids, the RNA and DNA,
which are the genetic materials of all life forms
and are important for the recognition of the
pathogens in case diseased condition, i.e.,
those nucleic acids act as signaling agents. The
toll like receptors (TLRs) like TLRs, TLR3,
TLR7, TLR8, TLR9 are localized in endosomes
and recognizes nucleic acids. Especially TLR7
& TLR8 recognizes single stranded RNA,
TLR13 recognizes bacterial 23sRNA which in
turn activates downstream signaling pathways to induce inflammatory responses [14].
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1. Structures and functions of biomolecules
2. Structure Activity Relationship (SAR)
Structure Activity Relationship is the study used for the analysis of biological activity of a
target compound from its molecular or chemical structure. This concept was proposed by
Crum-Brown and Fraser in 1865. This concept is very useful in drug discovery during the
screening and optimization of the properties of new molecules. By this study, the chemical
structure of a molecule gives an estimation of its biological effect [12].
There is a special case in SAR called Quantitative Structure Activity Relationship (QSAR)
in which the relationship is quantified [12]. This model of SAR works in two stages, in first
stage it maps the relationship between the predictor variables (the physicochemical properties of the compound being tested) and the response variables (biological activity of the receptor under test). In the second stage, it gives the behavior of the new compound. In this QSAR
model, the biological effect can be expressed in quantitative form as the concentration of the
compound required to give certain biological activity (Fig. 1.2).
➢ Screening is the examination of chemical compound in a systematic manner to identify
the lead molecule. The identification of the lead molecule can be done by random
screening, nonrandom screening, drug metabolism studies, observation of side effects.
➢ Pruning is the refinement of the lead structure of the molecule, which determines the
pharmacophore.
➢ Pharmacophore is the spatial arrangement of the functional group which is responsible
for the biological response.
Recent research has demonstrated that phenolic polysaccharides with monomeric phenolic
acids and diferulic acids have potent in vitro antioxidant properties. There are generally few
FIG. 1.2 Outline of SAR study.
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3. Ligands
13
systematic studies describing the structure-function connections of antioxidative carbohydrate polymers. Additionally, the significant polymer variability has made it extremely difficult to develop consistent structure-function connections. The structure-function relationships
of purified and characterized carbohydrate polymers isolated from various medicinal plants,
either directly or after selective structural modifications, have been established by researchers, and on the basis of the accumulated data, these common structural motifs that
are crucial for antioxidant activity emerge [15].
Bioactive peptides are brief sequences with a length of 2e20 amino acids that have positive
physiological effects when taken in vivo. They can be liberated by proteolytic hydrolysis using commercially available enzymes, proteolytic microbes, and fermentation techniques even
though they are inactive within the parent proteins’ sequence [16].Bioactive peptides can
directly enter the bloodstream after being absorbed in the intestine, ensuring their bioavailability in vivo and a physiological response at the target region [17].
Long known for their antibacterial effects, Fatty acids (FA) are interestingly created by
plants and algae to protect themselves from diseases, such as multidrug-resistant bacteria
(MDRB) [18].Since these substances might be the next generation of antibacterial drugs to
treat and prevent bacterial infections, the fact that FA have antibacterial action against
MDRB may be important for the Center for Disease Control and Prevention (CDC). Although
FA’s antibacterial action has been covered in a number of papers, the apparent various pathways by which FA confers its antibacterial activity are unclear and require further investigation [19].
2.1 Need for the SAR study
U In the field of medicinal chemistry, it helps to tune the properties of new drug during
its developmental phase thereby helps to enhance its potency [12].
U SAR helps to produce new drugs having similar properties of the existing drugs by
providing the structural details [12].
U SAR helps to estimate the toxicity of the compounds.
U SAR can give the interaction pattern between the drug and receptor under study.
U SAR can be used to study the solubility, reaction rate, distribution, metabolism and
excretion of the drug being tested.
U The side effects of the compound which is being tested can also be known [20].
3. Ligands
The word ‘ligand’ is of Latin origin, which means ‘to bind’. The ligand is any chemical substance that binds to the receptor with specificity. For example, drug is also a ligand. A ligand
is smaller in size than that of the receptor. The structure of the ligand and the receptor both
play a critical role as even a small change can alter the biological effect or response of the receptor molecules. The ligand and receptor binding can either be reversible or irreversible. The
interaction between the ligand and the receptor can either activate the receptor or inhibit the
receptor. The ligands can be classified into different types based on various aspects like structure of molecular complex, binding sites, chemical nature etc.[21].
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1. Structures and functions of biomolecules
3.1 Classification of ligands
i) Based on the number of binding sites/donor sites present in the ligand.
Name of the ligand
Example
Monodentate ligand: bind to only one site of the receptor.
Chlorine ion (Cl), Bromine ion (Br)
Bidentate ligand: bind to two sites of the receptor.
Phenanthroline, Oxalate ion
Polydentate ligand: Bind to more than two sites of the receptor.
Ethylene diamine tetra acetate (EDTA),
Diethylene triamine
ii) Based on chemical nature of ligand molecule.
Name of the ligand
Example
Inorganic ligands: molecules either of ionic nature or of inorganic forms of
chemical compounds
Fluoride (Fl), Iodide (I)
Neutral organic ligands: molecules which are organic in nature and do not
possess any charge on them.
Pyrazine
Anionic organic ligands: molecules which are organic in nature and possess
negative charge due to presence of highly electronegative atoms.
Oxygen, Nitrogen
Cationic organic ligands: molecules which are organic in nature and possess
positive charge due to the presence of pentavalent nitrogen atoms.
Pyridine based ligands like
oxadiazole
iii) Based on pharmacological activities of ligands (pharmacological classification).
The ligands are pharmacologically classified based on the aspect of their interaction with
the receptor molecules including how the ligand binds to the receptor i.e., reversible binding
or irreversible binding, and what is the effect of binding of ligand molecule on the receptors
which means whether it is stimulating the response of the receptor or not. The ligands are
classified into two major types based on the effects upon binding to the receptors, they are
named as “Agonist” and “Antagonist” [21].
Agonists and their action: Agonists are the molecules which upon binding to the receptor
produce biological response of the receptor by activating it. There occurs a conformational
change in the receptor molecule upon the binding of agonist molecule which is responsible
for the enhanced or induced response of the receptor [21]. The agonists are classified into
three types.
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4. Receptors
Name of the ligand
Example
Full agonist: ligand molecule that increases the activity and
produce maximum response.
Full agonist opioids like heroin, methadone etc
Partial agonist: ligand that increases the activity of the receptors
partially but do not produce maximum response as that of full
agonist.
Buspirone, aripiprazole, nalmefene etc
Inverse agonist: ligand that decreases the activity of the active
receptor and bring back the receptors to inactive state.
Beta blockers carvedilol, bucindolol are inverse
agonist at beta adrenoceptors.
Antagonists and their action: Antagonists are the molecules which upon binding to the
receptors block the biological response which is tend to be activated by agonists. The antagonists on binding to the receptors block the agonist binding and inhibits the signal produced
by receptor-agonist binding [21]. There are two types of antagonists, they are reversible
(competitive and noncompetitive antagonists) and irreversible antagonists.
Name of the ligand
Example
Competitive antagonist (reversible): The antagonists compete with the agonists
for the orthosteric sites to bind to the same receptors.
Naloxone, atropine
Non-competitive agonist (reversible): The antagonists will not compete with agonists
instead they bind at different sites of receptors called allosteric sites.
Cyclothiazide, ketamine
Irreversible antagonist: Agonists may or may not compete with the agonists for
binding to orthosteric sites, but they bind irreversibly.
Phenoxybenzamine
4. Receptors
Receptors are the proteinaceous molecules having specific binding sites for the ligand molecules to bind and thereby elicit a biological response. The biological response is the result of
the interaction between the ligand molecule and the receptor binding site. The receptors are
mainly of four different types [22].
4.1 Classification of receptors
The four major types of receptors are as follows:
1. Ligand gated ion channels
2. G-protein coupled receptors (GPCRs)
3. Enzyme linked receptors
4. Intracellular receptors
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1. Structures and functions of biomolecules
1. Ligand gated ion channels: As the name indicates, these receptors are responsible
for channelizing the ions toward inside the membrane only after the binding of the
ligand molecule to the binding site of the receptor. The binding of ligand to the receptor changes the shape of the receptor which allows the opening of the ion channels and inward movement of specific ions occur. For example: Nicotinic
Acetylcholine receptors, g-aminobutyric acid (GABA) receptor etc. [12].
2. G-protein coupled receptors: These are also called “7 Transmembrane receptors” as
they possess seven membrane spanning helices, which are entwined across plasma
membrane for seven times. These are the largest cell surface receptors in the eukaryotes. The G protein is made of three subunits, alpha, beta and gamma. The binding
of ligand to this receptor activates the G protein. The activated G-protein triggers the
production of a number of secondary messengers (the small molecule that initiates,
coordinates the intracellular signaling pathways, for example, cyclic AMP, Diacylglycerol). For instance, the activated G protein, which means the GTP bound alpha subunit can in turn activate the adenylyl cyclase enzyme to produce cyclic AMP (cAMP)
from ATP molecules, which is involved in response to sensory inputs, nerve transmission and hormones etc. These G-protein coupled receptors are of four subclasses
classes A (rhodopsin), B (secretin and adhesion), C (glutamate), and F (Frizzled)
based on their amino acid sequence [12].
3. Enzyme linked receptors: These are the transmembrane receptors which possess a
catalytic site in the cytoplasm. When the ligand molecule binds to these receptors,
they activate the catalytic site which is responsible for the enzymatic activity. For
example, we can consider the receptor tyrosine kinase. It gets autophosphorylated
upon the binding of ligand molecules which triggers the enzymatic activity of the receptor like many growth signals are associated with tyrosine kinase receptor.
4. Intracellular receptors: These are also called cytoplasmic receptors or internal receptors. As the itself defines, these are present inside the cytoplasm. These receptors are
responsible for the alteration of mRNA synthesis and thus the protein synthesis. The
ligand molecule must be of hydrophobic nature as it needs to go inside the membrane and bind to the cytoplasmic receptor. For example, Progesterone and androgen
receptors.
4.2 Some of the examples of the receptors acting as therapeutic targets
Receptors
Diseases/disorders
References
Class A GPCRs (rhodopsin like family)
Subclasses: aminergic, peptide, protein, lipid,
melatonin, nucleotide, steroid receptors.
Cardiovascular diseases, hypertension, pulmonary [23]
diseases, depression, migraine, glaucoma,
Parkinson’s disease to schizophrenia, cancerrelated fatigue etc
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5. Conclusion
dcont’d
Receptors
Diseases/disorders
References
Class B GPCRs (secretin and adhesion family)
Subclasses: vasoactive intestinal peptide (VIP),
pituitary adenylate cyclase-activating peptide
(PACAP), corticotropin-releasing factor (CRF),
parathyroid peptide hormone (PTH), growth
hormone-releasing hormone (GHRH), calcitonin
gene-related peptide (CGRP), glucagon, and
glucagon-like peptides (GLPs).
Obesity, T2DM, osteoporosis, migraine,
depression, and anxiety
[23]
Class C GPCRs (glutamate family)
Subclasses: 1 calcium-sensing receptor (CaSR), 2
gamma-aminobutyric acid (GABA) type B
receptors (GABAB1 and GABAB2), 3 taste 1
receptor (TS1R1e3), 8 metabotropic glutamate
receptors (mGluR1e8), and 8 orphan GPCRs.
Pain, migraine, Parkinson’s disease, Fragile X
syndrome, etc.
[23]
Toll like receptors (TLRs)
TLR4
TLR2, TLR6, TLR4, and TLR9
Septic shock
Recognition of fungi and their cellular
components, particularly cell wall components
[24]
Receptor tyrosine kinases (RTKs)
Cancer (reduced proliferation, increased
apoptosis, reduced migration)
[25]
Adenosine receptors (ARs)
Pulmonary disorders, cancer, Parkinson’s
disease and congestive heart failure etc
[26]
Purinergic receptors in airways
Asthma and other pulmonary disorders
[27]
Fibroblast growth factor receptor (FGFR)
Cancer
[28]
5. Conclusion
These biomolecules are the nonliving entities but the integral part of living organisms for
their existence. All the biomolecules act like a chain link through their involvement in the
metabolic processes of living organisms. For instance, the glucose is the basic sugar (carbohydrate) that circulates in the blood of higher animals which provides energy for the metabolic
processes. If we consider proteins, most of the enzymes, receptors and hormones are nothing
but protein molecules which stimulates the biological processes by acting as catalyst, signal
transducing agents and chemical messengers respectively. Then the lipids, the phospholipid
forms the outer cell membrane thus acts as selective barrier and the triacylglycerols helps to
maintain stable internal body temperature. Finally, the nucleic acids are the major biomolecules which store and transfer the genetic data and also directs the process of protein synthesis. The coordination of all these biomolecules is very much needed to perform their specific
functions for the existence of life.
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1. Structures and functions of biomolecules
References
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[2] Biology Articles, Tutorials and Dictionary Online. Biomolecule - definition and examples - biology online dictionary. 2022. Available from: https://www.biologyonline.com/dictionary/biomolecule.
[3] Holesh JE, Aslam S, Martin A. Physiology, carbohydrates. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. Available from: http://www.ncbi.nlm.nih.gov/books/NBK459280/.
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