Secondary Metabolites

Introduction
We live in the chemical world in which plants and microorganisms synthesize a diverse array of natural products. The remarkable developments in the field of biochemistry has led to the identification of the roles that each of these natural products plays in the lifecycle of an organism. Few examples to quote are, fatty acids as components of lipid structures, a-amino acids as building units of the ubiquitous proteins, and the heterocyclic purine and pyrimidine bases as elements of nucleic acid structure that embody the genetic code. The pathways by which they are synthesized are similar if not identical in all organisms and these natural products are in consequence frequently referred to as primary metabolites.

Apart from the primary metabolites plants and micro organisms synthesize a diverse array of natural products which do not play any explicit role in the life cycle of the organism producing it, for this reason they are called as secondary metabolites. The term secondary metabolites includes natural products, such as alkaloids, terpenes, phenols, polyacetylenes, polyenes, pigments, cyanogenic glycosides, glucosinolates, nonprotein amino acids, etc., that appeal to our sense of taste, our sense of smell and our sense of vision; Though these products are not ascribed any role in the host organism, we use them in our daily life.

Secondary metabolites are broadly classified into two groups based on the presence or absence of the nitrogen
Secondary metabolites without nitrogen includes
Terpenes- mono, di, tri and tetra terpenes
Phenolics- Flavonoids, polyacetylenes, polyketides, phenylpropanoids

Secondary metabolites with nitrogen includes
Alkaloids
Amines
Nonprotein amino acids
Cyanogenic glycosides
Glucosinolates

Terpenes
The volatile fractions of essential oils containing a number of C10H16 hydrocarbons are called as terpenes. The five carbon unit isoprene is identified as the building block of terpenes, this led to the formulation of biogenetic isoprene rule, which states that the carbon framework of a terpenoid substance should be regularly divisible into isoprene units. Terpenoid compounds, and their derivatives, are probably the most abundant and widely distributed of all higher-plant secondary metabolites. The analogues of terpenes with oxygen are called as terpenoids. Based on the number of isoprene units the terpenes are further classified, however higher plants contains the following terpenoids.
Monoterpenes, C₁₀H₁₆- Geraniol, Menthol, Camphene, Camphor
Sesquiterpenes, C₁₅H₂₄- Gossypol
Diterpenes, C₂₀H₃₂- Taxol, Abietic acid, Marrubin
Triterpenes, C₃₀H₄₈, - Cucurbitacin-E
Tetraterpenes, C₄₀H₆₄- ß-carotene

Phenols
The complex phenolic structural polymers found as integral cell-wall constituents of all vascular plants are described by the umbrella term Lignin (lignum, wood). Lignins are synthesized in vivo by the oxidative polymerization of three phenolic alcohols, p-coumaryl, coniferyl and sinapyl alcohols.

Hydroxycinnamate pool constituted by various intermediate C6.C3 acids (p-coumaric, ferulic, sinapic and the related caffeic) is the principal source of another major and very widely distributed group of phenolic compounds. Phenolic compounds show a huge structural diversity, the structure of these compound ranges from a very simple phenol, salicin to a very complex polyphenols, vegetable tannins. Ubiquitous phenolic conjugate, Chlorogenic acid constitutes 13% of the soluble matter of roasted coffee beans, a cup of instant coffee contains 0.25g of this compound.

Acetate (acetyl-coenzyme A), is the alternative building unit employed in the synthesis of plant phenols, e.g. tetrahydocannabinol.

Since phenols are readily oxidized their inclusion in diet may plausibly reduce the chronic diseases such as cancer and atheroschlerosis. The oxidative ability of the phenols has been exploited in the manufacture of both cocoa and tea by fermentation of the raw plant materials. Plant flavonoid like cyanin, quercetin and isoflavonoids like phenolic ether rotenone from Derris elliptica, a plant known for centuries for its insecticidal and fish poisoning properties also constitutes the phenolic metabolites.

Alkaloids
These compounds show alkali like nature, hence the name alkaloids. Alkaloids play a major role in traditional medicine, the list of drugs of plant origin used for treating different ailments is increasing day by day and complementing modern medicine. For many years humans have exploited the plants for therapeutic purposes, for murder and hunting, for enjoyment, for magic and for communication with the gods. One such classical example is the murder of Socrates with a draught of hemlock (Conium maculatum) whose crucial ingredient is coniine. Nearly 500 years ago, South American explorers reported the use of curare (a crude extract of chondrodendron tomentosum) tipped arrows by Indians for hunting. Seventy years back the most potent constituent of curare (tubocurarine) was isolated and has been exploited in surgery to aid in muscle relaxation.

The earliest medicinal plants used by man are of the genus Papaver. From the day of its discovery in 1817, morphine has been used in treatment of deep-seated pain. The extracts of Erythroxylon coca are used in the formulation of the beverage Coca Cola. Coniine, nicotine, strychnine, tubocurarine, morphine and mescalin are all examples of alkaloids. Both acetate and mevalonate contributes the building blocks for the synthesis of alkaloids. Precise definition of alkaloids has been very hard to achieve as a result several metabolites, though not basic are often classified as alkaloids. Typical examples are caffeine and its desmethyl derivative theobromine. Coffee is obtained from the roasted seeds of Coffea arabica and tea from leaves of Camellia sinesis, a typical cup of tea or coffee contains about 0.1g of the stimulant caffeine. Theobromine is the stimulant of cocoa and chocolate.

Secondary metabolites characteristics
Secondary metabolites from plant and microorganisms displays distinctive features summarized below

Structural diversity
Secondary metabolites show a great structural diversity. This structural diversity has been accomplished by the addition of different chemical groups to the key intermediate. Endless variations are played up on a single chemical theme. This diversity also indicates the nature’s unrestrained spending in synthesizing novel compounds.

Taxonomic distribution
Secondary metabolites show a distinct pattern of distribution in nature, some of them have an almost universal occurrence in plants while a majority seems to have much more restricted taxonomic distribution. Alkaloids are more taxonomically distributed, for example cocaine and morphine are only found in Erythroxylon coca and Papaver spp.

Accumulation and Storage
Secondary metabolism is regularly characterized by the accumulation of particular metabolites. The list of secondary metabolites under human exploitation in quite big, few examples of the list includes morphine constituting about 10% in the dried juice of unripe seed pod of Papaver somniferum; 13% of the water-soluble matter of coffee beans is chlorogenic acid.

Induction and regulation
The initiation of secondary metabolism depends up on the vegetative state of the organism and to a range of other parameters like, morphological, cytological, availability of nutrients, external stress, etc. Chemical and morphological specialization often appear to go hand in hand.

Biosynthesis
Majority of the secondary metabolites are derived from a handful of key intermediates of primary metabolism. Acetate, a principle intermediate of acetyl co-enzyme A, melonyl-coenzyme A, mevalonate paves the path for the derivation of large number of secondary metabolites. Similarly large number of secondary metabolites are derived from certain protein a-amino acids, L-valine, L-leucine, L-isoleucine, L-tyrosine, L-phenylalanine, L-tryptophan, L-lysine, l-ornithine and L-proline. In contrast to the technical developments, the details of the molecular biology of the secondary metabolism- the genetic material, its expression, encoding enzymes and of the specific enzymes themselves in many cases is much more limited.

Anaerobic organisms are poor sources of secondary metabolites. Structural diversity, based on chemical embroidery of a key intermediate is often dependent on the oxygen requiring mechanisms. Taxol, a diterpenoid used in the treatment of breast cancer is derived from acetate, via mevalonate, geranylgeranylpyrophosphate, and subsequent oxygenation at eight positions on the hydrocarbon skeleton.

Significance
Plants have an extraordinary synthetic skills. Starting with the water, carbon dioxide and mineral salts, they synthesize large number of structurally distinct essential primary metabolites as well as a series of secondary metabolites. It is quite interesting to know how the particular secondary metabolite come into being within a particular cells or even particular subcellular compartments. How did the compound specifically present in a particular plant species and how do the synthesis of secondary metabolites regulated. But answers to the above questions have been obtained partly pointing the ways forward. Secondary metabolites are very important for the interactions between the organism and its environment. The secondary metabolites identified so far may fall into several broad categories:

• Secondary products as hormones and signal agents
• Secondary products as pheromones
• Secondary products mediating ecological interactions (allelochemicals)

Plant secondary products that act as hormones and signaling agent

S. No	Scecondary metabolite	Type of secondarymetabolite	Function
1	Abscisic acid	Sesquiterpene	Plant growth regulators
2	Gibberellic acid	Diterpene
3	Brassinosteroids	Triterpene
4	Indole acetic acid	-
5	Ethene	-
6	Jasmonic acid	-	Signal molecule for activation of plant defence response
7	Salicylic acid	Phenolic

Plant secondary products that act in defence and allelopathy

S. No	Scecondary metabolite	Type of secondarymetabolite	function
1	Senecione in ragwort (Senecio jacobaea)	Pyrrolizidine alkaloid	Deterrence of mammalian herbivores
2	Pyrethrin-1	Terpene derivatives	Insect antifeedants and insecticides
3	Azadirachtin
4	Rishitin	norsesquiterpene alcohol	Antifungal compound
5	Vegetable Tannins	Phenolics	Chemical defence
6	Naphthoquinone juglone from walnut (Juglans nigra)	Phenolics	Acidification of soils and creates nutrient-deficient environments leading to inhibition of growth of other seedlings
7	Cruciferae sinigrin	Glucosinolate	Deterrence of insects but positive feeding stimulus to cabbage butterflies and cabbage aphids

In contrast to the defence, secondary metabolites also aid in attracting pollinators and seed dispersal agents in the form of nectar, the pigments colouring the flowers and floral scents.

Detoxification strategies developed by the host plant to prevent auto toxicity of secondary metabolites
Plants produce a wide variety of secondary metabolites which play a key role in plant defence against the predators, it is quite interesting to know how the host plant escapes the toxic effects of these compounds. Plants have developed various mechanisms to sequester these toxic secondary metabolites to negate their adverse effect, primary among these mechanisms is the storage of water soluble compounds in vacuole to avoid them from coming in contact with the cellular machinery which otherwise could cause serious consequences. Liphophilic substances are sequestered in specialized structures like resin ducts, laticifers, glandular hairs, trichomes, in the cuticle or on the cuticle. Other detoxification mechanisms include the storage of the secondary metabolites as a conjugated compound there by reducing the toxicity of the compound and by producing the precursors of the active compounds which will be easily activated up on plant damage.

List of major and widely used secondary metabolites

S.No	compound	Source	Class	Effects/uses
1	Geraniol	Constituent of rose oil	Monoterpenes	Used in preparation of perfumes
2	Menthol	Mint and relative plants		Interfere with neurotransmission, block ion transport, anesthetic. Used for defence against insects
3	Camphene	Minor constituent of many essential oils such as turpentine, cypress oil, camphor oil, citronella oil, ginger oil		Used in preparation of fragrances and food additive for flavoring
4	Camphor	Cinnamomum camphora		Used in religious ceremonies and cooking
5	Abietic acid n	Pinus species	Diterpene	Insect anti-feedant
6	Gossypol	Cotton	Seaquiterpene	Block phosphorylation; toxic
7	Cucurbitacin-E	Cucurbitaceae	Triterpenes	Anti-inflammatory, antioxidant
8	Marrubin	Marrubium vulgare		Anti-diabetic and anti-inflammatory
9	Digitogenin	Digitalis (foxglove)		Stimulate heart muscle, alter ion transport
10	Carotene	Many plants	Tetraterpene	Antioxidant; imparts orange color
11	Eugenol	Eugenia aromatica	Phenolic	Gives the odor, flavor and antimicrobial
12	Zingerone	Zingiber officinalis	Phenolic	Flavor additive and antidiarrheal
13	Curcumin	Curcuma longa	Phenolic	Spice pigment and anti-inflamattory
14	Rotenone	Derris elliptica	Phenol-ether	Insecticidal
15	Coniine	Conium maculatum (poison hemlock)	Alkaloid	Neurotoxin
16	Tubocurarine	Chondrodendron tomentosum	Alkaloid	Used as muscle relaxant in surgery
17	Morphine	Papaver genus members	Alkaloid	Used to treat deep seated pain
18	Cocaine	Erythroxylon coca	Alkaloid	Used as anaesthetic agent in surgery
19	Nicotine	Tobacco and coca plant	Alkaloid	interfere with neurotransmission, block enzyme action
20	Mescalin	Lophophora williamsii	Alkaloid	Hallucinogen
21	Caffeine	Camellia sinensis, Coffea arabica	Alkaloid	Stimulant
22	Taxol	Taxus brevifolia	Diterpene	Cytotoxic, used in treatment of breast cancer
23	Vinblastine	Catharanthus roseus	Alkaloid	Cytotoxic, used in treatment of breast cancer
24	Tannin	Widely distributed in many plant species	Phenolic	Feeding deterrents
25	Salvianin	Salvia splendens	Phenolic	Floral pigment
26	Spinasterol	Spinach	sterols	Interfere with animal hormone action
Miscellaneous secondary metabolites
27	Canavanine	Canavalia ensiformis	Non protein amino acids	Deterrence of mammalian herbivores
28	Alliin	Onion and garlic		Antioxidant and imparts aroma
29	Azetidine-2-carboxylic acid	Convallaria majalis		Deters the growth of predators
30	Sinigrin	Crucifirae members	Glucosinolate	Defensive factor against insects, as well as positive feeding stimulus to cabbage butterflies and aphids

Published date : 31 May 2014 05:00PM