Pharmacological Role of Biosynthetic Products

*Yakubu Jibira and Paul Atawuchugi*

## **Abstract**

A product such as hydrated carbons (carbohydrates), lipids, proteins, and nucleic acids play significant roles in plants metabolically. But there are other natural organic products manufactured by plants, some of the products are complex molecules, which are not primary metabolites. These biosynthetic products have possesses a variety of therapeutic merits in drug discovery. Some biosynthetic products show numerous appreciable therapeutic effects making them beneficial for trimming down polypharmacy and as viable candidates for the management of chronic diseases such as diabetes and hypertension in patients. The chapter discusses the pharmacological role of some biosynthetic products from plants and animals.

**Keywords:** alkaloids, phytosterols, biosynthesis, amino acids, pharmacological, terpenes

## **1. Introduction**

Natural products are mostly produced by a living organism. A product such as carbohydrates, lipids, proteins, and nucleic acids play significantly impact on the primary role in in plants in terms of their metabolic reactions. Moreover, other natural organic compounds have also been known to be produced by plants, with which some of them are complex molecules, which are not primary metabolites. Different organisms may produce the same compounds through different pathways (e.g., convergent evolution), even if they are widely separated phylogenetically. The same organism may produce some compounds via over one biosynthetic path. There may be over one path available, such as in a changed linear process or metabolic grid. Even if the same compound is present in two different organisms, they may be formed via different pathways. This, however, is more likely for metabolites with simple structures. It derives the major precursors from the metabolism of carbohydrate (sugars), protein (amino acids), and lipid (fatty acid). The pathway derived biosynthetically for aromatic amino acids is an integral source of aromatic compounds such as flavonoids, phenols, and some alkaloids. Glycolysis yields an important metabolite such as acetyl-CoA and also via the beta-oxidation of fatty acids and also used in the tricarboxylic acid cycle (TCA) in the manufacture of organic acids, which are also starting materials for secondary metabolites. Also, acetyl-CoA plays important role in synthesizing terpenes, which forms a distinct class of metabolites.

#### **2. Animal biosynthetic product**

Animals contain many unique small molecules, including bioactive secondary metabolites. The compounds are protective, offensive or involved in communication [1]. Most of this product is also biologically effective, and they include the following.

#### **2.1 Terpenes**

Terpenes occur widely in nature. They are a large and varied class of hydrocarbons, which are produced by a wide variety of plants and by some animals. Terpenes are biosynthetically derived from isoprene units with the molecular formula C5H8. In bacteria and plants, isoprene precursor's dimethylallyl pyrophosphate and isopentenyl pyrophosphate can be made either via the mevalonate or deoxyxylulose phosphate pathways, but in animals' mevalonate is the source of these precursors [2]. The mevalonate pathway is the universal source of the terpenoid C5 precursor's isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). In this pathway, three molecules of acetyl-CoA are condensed to 3-hydroxy-3-methylglutaryl-CoA with subsequent reduction to mevalonate, which is converted to IPP and DMAPP. Terpenes can exist as hydrocarbons or have oxygen-containing compounds such as hydroxyl, carboxyl, ketone, or aldehyde groups. After chemical modification of terpenes, it refers to the resulting compounds as terpenoids [3].

In the biochemical pathway of terpenoid synthesis, prenyltransferases take part in the condensation of activated forms of isoprene units. They link IPP with an isopentenyl diphosphate isomer of DMAPP in a "head-to-tail" manner. The linear chains of phenyl diphosphates that are formed in the reaction may also be changed through dimerization or cyclization by terpene synthase, forming terpenoids with new functions. They classify the resulting terpenes in order of size into hemiterpene, monoterpenes, sesquiterpenes, diterpene, triterpene, tetra terpenes, and polyterpenes. Hemiterpene comprises a single isoprene unit and changed into oxygen-containing derivatives called hemiterpenoids [3].

We have found terpenoids to be useful in the prevention and therapy of several diseases, including cancer, and also to have antimicrobial, antifungal, antiparasitic, antiviral, anti-allergenic, antispasmodic, antihyperglycemic, anti-inflammatory, and immunomodulatory properties [3].

#### **2.2 Carnitine**

Vaz and Wanders, [4] have described that carnitine plays a vital role in energy production in living organisms in terms of metabolism since it enables activated fatty acids to enter the mitochondria, where broken down via β-oxidation. Carnitine is present in all animal species, including other multiple micro-organisms and plants. They maintain its homoeostasis through endogenous synthesis, absorption from dietary sources and efficient tubular reabsorption by the kidney. Animal tissues contain relatively high amounts of carnitine, varying between 0.2 and 6 μmol/g, with the highest concentrations in heart and skeletal muscle. Apart from the diet being the primary source of carnitine, most mammals can synthesize carnitine internally [4].

Carnitine synthesis is from two amino acids; precisely lysine and methionine. Lysine serves as the carbon backbone of carnitine and the 4-N-methyl groups emanate from methionine [5]. Proteins in mammals contain N'trimethyl-lysine (TML) residues. N-methylation of these lysine residues occurs as a post-translational event in proteins such as calmodulin, myosin, actin, cytochrome c and

**9**

**2.3 Pheromone**

*Pharmacological Role of Biosynthetic Products DOI: http://dx.doi.org/10.5772/intechopen.96977*

histones. This reaction mostly catalysed by specific methyltransferase, which uses S-adenosylmethionine as a methyl donor. TML is the first metabolite of carnitine biosynthesis is released through the action of Lysosomal hydrolysis of these proteins. TML is first hydroxylated on the 3-position by TML to yield 3-hydroxy TML (HTML). Aldolytic cleavage of HTML yields 4-trimethylaminobutyraldehyde (TMABA) and glycine, a reaction catalysed by HTML aldolase (HTMLA; EC 4.1.2.'X'). Dehydrogenation of TMABA by TMABA dehydrogenase (TMABA-DH; EC 1.2.1.47) results in the formation of 4-Ntrimethylaminobutyrate (butyrobetaine). In the irrevocable step, butyrobetaine is hydroxylated on the 3-position by γ-butyrobetaine dioxygenase to yield carnitine [4]. Carnitine has an important role in the transport of activated long-chain fatty acids from the cytosol to the mitochondrial matrix where β-oxidation takes place. Second, they involve carnitine in transferring the products of peroxisomal β-oxidation, including acetyl-CoA, to the

Pharmacologically, carnitine has possessed several effects on bone mass, male infertility, cognitive support, [6] metabolic function improvement, [7] neuroprotective effects in Alzheimer's dementia [8] and Parkinson's disease, [9] protection against oxidative stress damage, [10] congestive heart failure, hypertrophic heart disease, and peripheral arterial disease treatment [11]. They have also shown it to

From [13] the ability of an agent to control endothelial dysfunction is through upsetting the balance between the production of a vasodilator such as nitric oxide and vasoconstrictor, such as endothelin-1 substances in response to physical or chemical stimuli. This is because it is through that imbalance that leads to endothelial dysfunction, which is one of the initial steps in atherogenesis [14]. They relate endothelial dysfunction to cardiovascular risk factors such as arterial hypertension, dyslipidemia, diabetes, and obesity [15, 16]. They have therefore investigated carnitine gas in rats' models to cause an endothelium-dependent dilatation in arteries, since endothelial nitric oxide seemed to be the main mediator of vasodilatation [17]. For the cardioprotective ability of carnitine to serve as a cardioprotective agent, isolated rat working heart through different antioxidant mechanisms in most of the cases [18]. In terms of insulin resistance, this is where a 20 weeks treatment with carnitine in animal obese models resulted in a reduction in body weight, abdominal adiposity, plasmatic insulin, and liver triglyceride content [19]. Several, studies have been conducted on the antioxidant properties of carnitine and was due mainly to a reduction in both lipid peroxidation and free radical generation [20]. A decreased expression of inducible NO synthase and protein nitration, and inhibition of tubular necrosis and neutrophil infiltration in transplanted kidneys [21] . For antioxidant study [22] also revealed that carnitine and its derivatives fundamental mechanisms as participating in redox signalling that affects transcription factors

mitochondria for oxidation to CO2 and H2O in the Krebs cycle.

(Nrf2, PPARα, NF-κB, etc.) and activating the vitagene network.

Pheromone plays a key role in sexual communication and reproduction in many insects such as the moth's species. In some insects, the pheromone is biosynthesized and released by specialized sex pheromone glands (PGs) that are along the intersegmental membrane between the 8th and 9th abdominal segments of females. Although the general pathway of sex pheromone synthesis in most species has not been established and the molecular mechanisms remain poorly understood [23]. Although de novo synthesis is more prevalent in the species studied to date, there are multiple examples of pheromone components derived from host precursors. Sometimes, such as leucine, used as starting material for fatty-acid derived sex

improve peripheral vasodilator activity [12].

#### *Pharmacological Role of Biosynthetic Products DOI: http://dx.doi.org/10.5772/intechopen.96977*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

oxygen-containing derivatives called hemiterpenoids [3].

and immunomodulatory properties [3].

**2.2 Carnitine**

carnitine internally [4].

Animals contain many unique small molecules, including bioactive secondary metabolites. The compounds are protective, offensive or involved in communication [1]. Most of this product is also biologically effective, and they include the

Terpenes occur widely in nature. They are a large and varied class of hydrocarbons, which are produced by a wide variety of plants and by some animals. Terpenes are biosynthetically derived from isoprene units with the molecular formula C5H8. In bacteria and plants, isoprene precursor's dimethylallyl pyrophosphate and isopentenyl pyrophosphate can be made either via the mevalonate or deoxyxylulose phosphate pathways, but in animals' mevalonate is the source of these precursors [2]. The mevalonate pathway is the universal source of the terpenoid C5 precursor's isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). In this pathway, three molecules of acetyl-CoA are condensed to 3-hydroxy-3-methylglutaryl-CoA with subsequent reduction to mevalonate, which is converted to IPP and DMAPP. Terpenes can exist as hydrocarbons or have oxygen-containing compounds such as hydroxyl, carboxyl, ketone, or aldehyde groups. After chemical modification of terpenes, it refers to the resulting compounds as terpenoids [3]. In the biochemical pathway of terpenoid synthesis, prenyltransferases take part in the condensation of activated forms of isoprene units. They link IPP with an isopentenyl diphosphate isomer of DMAPP in a "head-to-tail" manner. The linear chains of phenyl diphosphates that are formed in the reaction may also be changed through dimerization or cyclization by terpene synthase, forming terpenoids with new functions. They classify the resulting terpenes in order of size into hemiterpene, monoterpenes, sesquiterpenes, diterpene, triterpene, tetra terpenes, and polyterpenes. Hemiterpene comprises a single isoprene unit and changed into

We have found terpenoids to be useful in the prevention and therapy of several diseases, including cancer, and also to have antimicrobial, antifungal, antiparasitic, antiviral, anti-allergenic, antispasmodic, antihyperglycemic, anti-inflammatory,

Vaz and Wanders, [4] have described that carnitine plays a vital role in energy production in living organisms in terms of metabolism since it enables activated fatty acids to enter the mitochondria, where broken down via β-oxidation.

Carnitine is present in all animal species, including other multiple micro-organisms

Carnitine synthesis is from two amino acids; precisely lysine and methionine. Lysine serves as the carbon backbone of carnitine and the 4-N-methyl groups emanate from methionine [5]. Proteins in mammals contain N'trimethyl-lysine (TML) residues. N-methylation of these lysine residues occurs as a post-translational event in proteins such as calmodulin, myosin, actin, cytochrome c and

and plants. They maintain its homoeostasis through endogenous synthesis, absorption from dietary sources and efficient tubular reabsorption by the kidney. Animal tissues contain relatively high amounts of carnitine, varying between 0.2 and 6 μmol/g, with the highest concentrations in heart and skeletal muscle. Apart from the diet being the primary source of carnitine, most mammals can synthesize

**2. Animal biosynthetic product**

following.

**2.1 Terpenes**

**8**

histones. This reaction mostly catalysed by specific methyltransferase, which uses S-adenosylmethionine as a methyl donor. TML is the first metabolite of carnitine biosynthesis is released through the action of Lysosomal hydrolysis of these proteins. TML is first hydroxylated on the 3-position by TML to yield 3-hydroxy TML (HTML). Aldolytic cleavage of HTML yields 4-trimethylaminobutyraldehyde (TMABA) and glycine, a reaction catalysed by HTML aldolase (HTMLA; EC 4.1.2.'X'). Dehydrogenation of TMABA by TMABA dehydrogenase (TMABA-DH; EC 1.2.1.47) results in the formation of 4-Ntrimethylaminobutyrate (butyrobetaine). In the irrevocable step, butyrobetaine is hydroxylated on the 3-position by γ-butyrobetaine dioxygenase to yield carnitine [4]. Carnitine has an important role in the transport of activated long-chain fatty acids from the cytosol to the mitochondrial matrix where β-oxidation takes place. Second, they involve carnitine in transferring the products of peroxisomal β-oxidation, including acetyl-CoA, to the mitochondria for oxidation to CO2 and H2O in the Krebs cycle.

Pharmacologically, carnitine has possessed several effects on bone mass, male infertility, cognitive support, [6] metabolic function improvement, [7] neuroprotective effects in Alzheimer's dementia [8] and Parkinson's disease, [9] protection against oxidative stress damage, [10] congestive heart failure, hypertrophic heart disease, and peripheral arterial disease treatment [11]. They have also shown it to improve peripheral vasodilator activity [12].

From [13] the ability of an agent to control endothelial dysfunction is through upsetting the balance between the production of a vasodilator such as nitric oxide and vasoconstrictor, such as endothelin-1 substances in response to physical or chemical stimuli. This is because it is through that imbalance that leads to endothelial dysfunction, which is one of the initial steps in atherogenesis [14]. They relate endothelial dysfunction to cardiovascular risk factors such as arterial hypertension, dyslipidemia, diabetes, and obesity [15, 16]. They have therefore investigated carnitine gas in rats' models to cause an endothelium-dependent dilatation in arteries, since endothelial nitric oxide seemed to be the main mediator of vasodilatation [17]. For the cardioprotective ability of carnitine to serve as a cardioprotective agent, isolated rat working heart through different antioxidant mechanisms in most of the cases [18]. In terms of insulin resistance, this is where a 20 weeks treatment with carnitine in animal obese models resulted in a reduction in body weight, abdominal adiposity, plasmatic insulin, and liver triglyceride content [19]. Several, studies have been conducted on the antioxidant properties of carnitine and was due mainly to a reduction in both lipid peroxidation and free radical generation [20]. A decreased expression of inducible NO synthase and protein nitration, and inhibition of tubular necrosis and neutrophil infiltration in transplanted kidneys [21] . For antioxidant study [22] also revealed that carnitine and its derivatives fundamental mechanisms as participating in redox signalling that affects transcription factors (Nrf2, PPARα, NF-κB, etc.) and activating the vitagene network.

#### **2.3 Pheromone**

Pheromone plays a key role in sexual communication and reproduction in many insects such as the moth's species. In some insects, the pheromone is biosynthesized and released by specialized sex pheromone glands (PGs) that are along the intersegmental membrane between the 8th and 9th abdominal segments of females. Although the general pathway of sex pheromone synthesis in most species has not been established and the molecular mechanisms remain poorly understood [23]. Although de novo synthesis is more prevalent in the species studied to date, there are multiple examples of pheromone components derived from host precursors. Sometimes, such as leucine, used as starting material for fatty-acid derived sex

pheromone biosynthesis by Holomelina spp. (Lepidoptera: Arctiidae), the putative plant-derived precursor is extensively elaborated by a typically de novo pathway. In other cases, it converts a highly elaborated host precursor to a pheromone component through a simple chemical transformation. While they originally reported the utilization of host precursors for pheromone biosynthesis in some insects, subsequent studies showed that pheromone biosynthesis was only or partially de novo [23].

The analysis of different pheromone glands in different species has revealed the occurrence of unusual fatty acids that have been proposed as precursors of pheromone components. Many lepidopteran sex pheromones are produced by P-oxidation steps with desaturase systems. However, only a few studies have a combination of different fatty acyl intermediates been used to show experimentally a pheromone biosynthetic pathway [23].

From [24] sex pheromone biosynthesis in moths begins with a palmitic or stearic acid moiety that is synthesized de novo in the PG through modifications of the fatty acid biosynthetic pathway. Through a series of enzymatic reactions such as desaturation, chain-shortening reaction, reduction, acetylation, and oxidation, it then converts the palmitic or stearic acids to the final pheromone components in a step-wise manner. Therefore, different enzymes are likely to be involved in the different reactions, and to date, the genes encoding 4 different classes of enzymes that are essential for this pathway have been functionally identified desaturases (Des), fatty acid reductases (FARs), fatty acid transport proteins (FATPs), and acyl-CoAbinding proteins (ACBPs) [24].

Pheromones, a chemical or blend of chemicals released by an organism that causes a specific behavioral or physiological reaction in one or more conspecific individuals are important mediators of communication for bacteria, plants, and animals in these environments. Pheromone systems of insects have proved to be some of the richest intellectual sources for the nascent science of chemical ecology the composite pheromones can be classed into six behaviorally functional groups: sex, aggregation, dispersal (spacing or epideictic), alarm, recruitment (trail), and maturation [24].

Pheromones are noted to function as opposite-sex attractants, same-sex repellents, and mother-infant bonding attractants and as menstrual cycle modulators [25]. A review article by [26] concluded that pheromones have aphrodisiac activity.

#### **2.4 Melanin**

Melanin is an abundant biological pigment that is present in mammalian which is located in areas such as skin, hair, eyes, ears and the nervous system. Birds' feathers, squid's ink, insects, plants and many other biological systems have been also known to contain melanin. It classifies melanin into three groups: eumelanin, pheomelanin and allomelanins. We term nervous system melanins as neuromelanin. Eumelanin colours commonly present as black or brown in animals [27].

Amino acid tyrosine is needed in the production of melanin, but its actions are catalyzed enzymatically by tyrosinase. In their primary biosynthetic pathway, tyrosine is hydroxylated to form the catecholamine 3,4-dihydroxyphenylalanine (DOPA), which is then oxidized to form 3,4-dioxyphenylalanine (dopa quinone) before cyclization to 5,6-indole quinones and their subsequent polymerization to form melanin [27].

Mason-Raper pathway can also produce melanin, and it started by the usage of tyrosine to form dihydroxyphenylalanine by tyrosinase through an oxidation reaction. The product (dihydroxyphenylalanine) formed is then oxidized by the same enzyme to dopa quinone, which rearranges spontaneously to leuco dopa chrome and then to dopa chrome. An unusual trait of dopa chrome that of decolorizing slowly if held

**11**

*Pharmacological Role of Biosynthetic Products DOI: http://dx.doi.org/10.5772/intechopen.96977*

in the structure.

under a vacuum allowed the identification of the subsequent intermediate 5,6-dihydroxy indole-2 carbolic acid, which loses its carboxyl group to become 5,6-dihydroxy dole. Upon exposure to air 5,6-dihydroxy indole is oxidized to indole 5,6-quinone and

It has revealed melanin from natural sources to exhibit a broad spectrum of biological activities such as UV radiation protection, enzymatic lysis, and damage by oxidants, and resistance to drugs by pathogens, protection of insects against bacteria and antiviral protection. They have shown melanin to chelate metal ions and to act as a physiological redox buffer [27]. With this in mind, several studies have pharmacologically shown that melanin is indeed effective as an antioxidant, [28–30] Immunomodulatory and enhancement, [31–34] hepatoprotective, [35]

Studies conducted in *Nigella sativa* L. by [38, 39] which contains a lot of melanin in its seeds had the potential of treating imbalanced cytokine production and unconcern cancer and other immunotherapies. This was possible because melanin

Melanins from various sources exhibit significant antioxidant activity, melanin protects pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which are then slowly released in nontoxic concentrations, Besides, melanin could also interact with orally administered drugs and a vehicle for drug delivery, Melanin extracted from different species of tea displays protective effects against hydrazine-induced liver injury, a remarkable anti-inflammatory effect of

The most ubiquitous sterol in the animal system is present as cholesterol. But plant lack cholesterol notwithstanding, they contain structurally similar other sterol and similar biosynthetic pathway exist both in plants and animals and some prokaryotes. In humans, Normal healthy adults synthesize cholesterol at a rate of approximately 1 g/day and consume approximately 0.3 g/day. A relatively constant level of cholesterol in the body (150–200 mg/dL) is maintained primarily by controlling the level of de novo synthesis, which is partly regulated in part by the

Cholesterol is biosynthesized from a 2-carbon metabolic intermediate, acetyl-CoA hooked end to end involving several enzymatic reactions and finally gets converted into the 27-carbon molecule of cholesterol. Metabolism (catabolism) of lipids, carbohydrates and proteins leads to the formation of AcetylCoA. The process of cholesterol synthesis has five major steps where the conversion of Acetyl-CoAs to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) is the first. HMG-CoA is converted to mevalonate, followed by the formation of an isoprene-based molecule, isopentenyl pyrophosphate (IPP), with the concomitant loss of CO2 from mevalonate. It, therefore, converts the IPP to squalene, where cholesterol is formed from squalene as the last step. The reaction is repeated with the units of Acetyl-CoA. Two moles of acetyl-CoA are condensed in a reversal of the thiolase reaction, forming acetoacetyl-CoA. Acetoacetyl-CoA and the third mole of acetyl-CoA are converted to HMG-CoA by the action of HMG-CoA synthase. HMG-CoA is converted to mevalonate by HMG-CoA reductase, HMGR (it binds this enzyme in the endoplasmic reticulum, ER). HMGR requires NADPH as a cofactor, and two moles of NADPH are consumed during the conversion of HMG-CoA to mevalonate.

then to melano chrome, a purple compound that polymerizes to melanin [27]. Similar to the biosynthesis of eumelanin, melanin known as pheomelanin is biologically synthesized, except that it incorporates a precursor containing sulphur

anticarcinogenic effects, [36] and anti-inflammatory [37].

induced TNF-alpha, IL-6 and VEGF mRNA expression.

melanin has been reported [34].

dietary intake of cholesterol [40].

**2.5 Cholesterol**

#### *Pharmacological Role of Biosynthetic Products DOI: http://dx.doi.org/10.5772/intechopen.96977*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

a pheromone biosynthetic pathway [23].

binding proteins (ACBPs) [24].

maturation [24].

**2.4 Melanin**

form melanin [27].

pheromone biosynthesis by Holomelina spp. (Lepidoptera: Arctiidae), the putative plant-derived precursor is extensively elaborated by a typically de novo pathway. In other cases, it converts a highly elaborated host precursor to a pheromone component through a simple chemical transformation. While they originally reported the utilization of host precursors for pheromone biosynthesis in some insects, subsequent studies showed that pheromone biosynthesis was only or partially de novo [23]. The analysis of different pheromone glands in different species has revealed the occurrence of unusual fatty acids that have been proposed as precursors of pheromone components. Many lepidopteran sex pheromones are produced by P-oxidation steps with desaturase systems. However, only a few studies have a combination of different fatty acyl intermediates been used to show experimentally

From [24] sex pheromone biosynthesis in moths begins with a palmitic or stearic

acid moiety that is synthesized de novo in the PG through modifications of the fatty acid biosynthetic pathway. Through a series of enzymatic reactions such as desaturation, chain-shortening reaction, reduction, acetylation, and oxidation, it then converts the palmitic or stearic acids to the final pheromone components in a step-wise manner. Therefore, different enzymes are likely to be involved in the different reactions, and to date, the genes encoding 4 different classes of enzymes that are essential for this pathway have been functionally identified desaturases (Des), fatty acid reductases (FARs), fatty acid transport proteins (FATPs), and acyl-CoA-

Pheromones, a chemical or blend of chemicals released by an organism that causes a specific behavioral or physiological reaction in one or more conspecific individuals are important mediators of communication for bacteria, plants, and animals in these environments. Pheromone systems of insects have proved to be some of the richest intellectual sources for the nascent science of chemical ecology the composite pheromones can be classed into six behaviorally functional groups: sex, aggregation, dispersal (spacing or epideictic), alarm, recruitment (trail), and

Pheromones are noted to function as opposite-sex attractants, same-sex repellents, and mother-infant bonding attractants and as menstrual cycle modulators [25]. A review article by [26] concluded that pheromones have aphrodisiac activity.

Melanin is an abundant biological pigment that is present in mammalian which

is located in areas such as skin, hair, eyes, ears and the nervous system. Birds' feathers, squid's ink, insects, plants and many other biological systems have been also known to contain melanin. It classifies melanin into three groups: eumelanin, pheomelanin and allomelanins. We term nervous system melanins as neuromelanin.

Amino acid tyrosine is needed in the production of melanin, but its actions are catalyzed enzymatically by tyrosinase. In their primary biosynthetic pathway, tyrosine is hydroxylated to form the catecholamine 3,4-dihydroxyphenylalanine (DOPA), which is then oxidized to form 3,4-dioxyphenylalanine (dopa quinone) before cyclization to 5,6-indole quinones and their subsequent polymerization to

Mason-Raper pathway can also produce melanin, and it started by the usage of tyrosine to form dihydroxyphenylalanine by tyrosinase through an oxidation reaction. The product (dihydroxyphenylalanine) formed is then oxidized by the same enzyme to dopa quinone, which rearranges spontaneously to leuco dopa chrome and then to dopa chrome. An unusual trait of dopa chrome that of decolorizing slowly if held

Eumelanin colours commonly present as black or brown in animals [27].

**10**

under a vacuum allowed the identification of the subsequent intermediate 5,6-dihydroxy indole-2 carbolic acid, which loses its carboxyl group to become 5,6-dihydroxy dole. Upon exposure to air 5,6-dihydroxy indole is oxidized to indole 5,6-quinone and then to melano chrome, a purple compound that polymerizes to melanin [27].

Similar to the biosynthesis of eumelanin, melanin known as pheomelanin is biologically synthesized, except that it incorporates a precursor containing sulphur in the structure.

It has revealed melanin from natural sources to exhibit a broad spectrum of biological activities such as UV radiation protection, enzymatic lysis, and damage by oxidants, and resistance to drugs by pathogens, protection of insects against bacteria and antiviral protection. They have shown melanin to chelate metal ions and to act as a physiological redox buffer [27]. With this in mind, several studies have pharmacologically shown that melanin is indeed effective as an antioxidant, [28–30] Immunomodulatory and enhancement, [31–34] hepatoprotective, [35] anticarcinogenic effects, [36] and anti-inflammatory [37].

Studies conducted in *Nigella sativa* L. by [38, 39] which contains a lot of melanin in its seeds had the potential of treating imbalanced cytokine production and unconcern cancer and other immunotherapies. This was possible because melanin induced TNF-alpha, IL-6 and VEGF mRNA expression.

Melanins from various sources exhibit significant antioxidant activity, melanin protects pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which are then slowly released in nontoxic concentrations, Besides, melanin could also interact with orally administered drugs and a vehicle for drug delivery, Melanin extracted from different species of tea displays protective effects against hydrazine-induced liver injury, a remarkable anti-inflammatory effect of melanin has been reported [34].

#### **2.5 Cholesterol**

The most ubiquitous sterol in the animal system is present as cholesterol. But plant lack cholesterol notwithstanding, they contain structurally similar other sterol and similar biosynthetic pathway exist both in plants and animals and some prokaryotes. In humans, Normal healthy adults synthesize cholesterol at a rate of approximately 1 g/day and consume approximately 0.3 g/day. A relatively constant level of cholesterol in the body (150–200 mg/dL) is maintained primarily by controlling the level of de novo synthesis, which is partly regulated in part by the dietary intake of cholesterol [40].

Cholesterol is biosynthesized from a 2-carbon metabolic intermediate, acetyl-CoA hooked end to end involving several enzymatic reactions and finally gets converted into the 27-carbon molecule of cholesterol. Metabolism (catabolism) of lipids, carbohydrates and proteins leads to the formation of AcetylCoA. The process of cholesterol synthesis has five major steps where the conversion of Acetyl-CoAs to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) is the first. HMG-CoA is converted to mevalonate, followed by the formation of an isoprene-based molecule, isopentenyl pyrophosphate (IPP), with the concomitant loss of CO2 from mevalonate. It, therefore, converts the IPP to squalene, where cholesterol is formed from squalene as the last step. The reaction is repeated with the units of Acetyl-CoA. Two moles of acetyl-CoA are condensed in a reversal of the thiolase reaction, forming acetoacetyl-CoA. Acetoacetyl-CoA and the third mole of acetyl-CoA are converted to HMG-CoA by the action of HMG-CoA synthase. HMG-CoA is converted to mevalonate by HMG-CoA reductase, HMGR (it binds this enzyme in the endoplasmic reticulum, ER). HMGR requires NADPH as a cofactor, and two moles of NADPH are consumed during the conversion of HMG-CoA to mevalonate.

The reaction catalyzed by HMGR is the rate-limiting step of cholesterol biosynthesis. Mevalonate is then activated by three successive phosphorylations, yielding 5-pyrophosphomevalonate. Phosphorylation mevalonate and successive reactions maintain their solubility since otherwise, these are insoluble in water [40].

Cholesterol from both diet and synthesis is utilized in the formation of membranes and the synthesis of the steroid hormones and bile acids, regulating membrane fluidity and permeability as a cell membrane structural component, formatting lipid rafts with sphingolipid to mediate cell-to-cell recognition, adhesion, and communication [40].

### **3. Biosynthesis of plant origin**

Different plants not only synthesize different aromatic secondary metabolites but also synthesize varying amounts of them at specific times and in specific subcellular compartments. One would expect that regulation of the differential biosynthesis of sometimes very complex molecular structures might involve regulation of the supply of the precursors influencing the rate-limiting step for carbon flow through the shikimate pathway. Recent data on transgenic potatoes give some sign that this is indeed the case [41].

#### **3.1 Biosynthesis of terpenoid compounds**

Some terpenoids play an important role in plant growth and development, such as gibberellin, as plant hormones regulate plant development. Other terpenoids play a role in the interaction between plants and the environment, such as participating in plant defence systems as phytoalexins and interspecies competition as interspecific sensing compounds. Terpenoids make up one of the largest and structurally diverse groups of naturally occurring compounds [42]. Mevalonic acid is mostly employed as a terpenoid synthetic racemate; however, mevalonic acid dimethoxy acetal may be resolved as its quinine salt. The acetates of the individual enantiomers of mevalonolactone are much less soluble than the racemate, and these may determine the purity and chirality of biosynthetic mevalonate. The steric course of many terpenoid biosynthetic processes has been followed using the stereospecifically deuterated and tritiated 2R,3R- [2-'H]-, 2S,3R- [2-3H]-, 3R,4R- [4–3 H] -, 3R,4S- [4- HI-, and 3R,5R- [S 3 H]-mevalonate. Several routes for preparing 5S- [5-3H] mevalonate have been described. [l-3H] Isopentenal is a substrate for liver alcohol dehydrogenase and this affords 1 s- [l-3H] isopentenyl, which may then be converted into mevalonic acid. Alternatively, [5-3H] mevalonic acid can be reduced enzymatically with mevalonate reductase to afford 5S-[5-3H] mevalonic acid. The hemithioacetal of mevalonate and coenzyme-A is reduced by 3-hydroxy-3-methylglutaryl COA reductase." The steric course of this reduction is now known and they can also adapt this to afford 3R,5S- [5-3H] mevalonic acid. They have reported a mevalonate kinase assay [13]. An enzyme system capable of forming the mono- and pyro-phosphates of mevalonic acid, isopentenyl pyrophosphate and dimethylallyl pyrophosphate has been isolated 'From orange-juice vesicles and shown to convert isopentenyl pyrophosphate and dimethylallyl pyrophosphate into linalool [42].

#### *3.1.1 Pharmacology of terpenoids*

Antitumour, [43] anti-inflammatory, antibacterial effects, cardiovascular effects, antimalarial, hypoglycemic effect, and transdermal absorption promotion have been investigated to give such pharmacological activities. Other activities apart

**13**

*Pharmacological Role of Biosynthetic Products DOI: http://dx.doi.org/10.5772/intechopen.96977*

*3.1.2 Works done on terpenoids*

**3.2 Biosynthesis of pinocembrin**

from the mentioned above include insect resistance, immunoregulation, anti-

They have conducted several studies on terpenoids and their outcomes are promising. For antitumour activity, they have shown that perillyl alcohol which contains terpenoids plays a preventive and therapeutic role in cancer. The results showed that the administration of perillyl alcohol in rats can significantly reduce the incidence and multiplicity of colonic invasive adenocarcinoma caused by the injection of carcinogen azomethane [43]. Paeoniflorin which is a monoterpene glycoside compound isolated from the root of *Paeonia lactiflora* gave significant levels of anti-inflammatory activity. It could also dose-dependently inhibit the production of inflammatory factor nitric oxide (NO), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) induced by lipopolysaccharides (LPS) [44]. Besides, menthol, which is a cyclic monoterpene, has been shown to have antibacterial activity [45], they found that menthol showed significant inhibitory activity of biofilm when studying the effects of plant-derived terpenoids on *Candida albicans*. Several studies have also shown that terpenoids, particularly artemisinin which is a sesquiterpene lactone compound isolated from *Artemisia annua* Linn, has an effective antimalarial activity and currently in use [3]. The latest findings suggest that tanshinone IIA (TS) which is a terpenoid can prevent the formation of atherosclerosis and the damage and hypertrophy of the heart. This is because of its ability to inhibit the oxidation of low-density lipoprotein and the expression of proinflammatory factors, and TS also

oxidation, antiaging, and neuroprotection have also been known [3].

has certain activity and potential to stabilize atherosclerotic plaque [46].

corresponding parameters in the synthetic pathways [47].

Pharmacologically, pinocembrin can exhibit anti-inflammatory, [48] antioxidant, [49] antibacterial [50] and neuroprotective activities [51]. They mainly use

*3.2.1 Pharmacological activities*

In plant propolis, pinocembrin is one of the most abundant flavonoid, and it could also be commonly found in a most plants. Biological synthesis plays a significant part in synthesizing pinocembrin owing to its increased yield and low cost in production. They can extract pinocembrin from product of nature but that methodology is of high production cost and reduced yield. Biological synthesis from microorganisms features the advantages of low cost and large product yield, which compensate for the lack pinocembrin natural sources [47]. *Escherichia coli* has been known to be used in the production of pinocembrin. Recently, efficient way of producing pinocembrin has been the main goal of most researchers. Biological production of pinocembrin mostly requires that one needs to supplement an expensive phenylpropanoid starting materials, resenting a key problem in previous studies. Genetic engineering is now the breakthrough in the synthesis of pinocembrin biosynthesis, where there is the usage of bacteria to construct the synthesis of pinocembrin from glucose. To manufacture the flavonoid precursor (2S)-pinocembrin directly from glucose, four-vectors have been assembled, 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase, chorismite mutase/pre-phenate dehydratase, phenylalanine ammonia-lyase (PAL), 4-coumarate: CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), malonate synthetase, malonate dehydratase, and malonate carrier protein. Pinocembrin synthesis from glucose can be achieved through adjustment of other

from the mentioned above include insect resistance, immunoregulation, antioxidation, antiaging, and neuroprotection have also been known [3].
