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NATURAL PRODUCTS
Man’s earliest interest in organic compounds goes back to prehistory, pigments for
dyeing, and painting, perfumes, and folk medicines are all organic compounds. And
required some crude extraction from their natural sources usually plants.
Many of such organic compounds from natural sources, often crystalline, were
isolated and purified in the early nineteenth century. The study of their reactions
constituted the beginning of organic chemistry. And indeed during the whole of the
century. These natural products constituted the main source of organic chemicals and
afforded the main problem of organic chemistry. Only with growth of synthesis was the
field freed from a dependence on compounds available from natural sources. However,
the variety of structures found in natural product is astonishing and most subtle (shrewd,
cunning) and challenging problems of the structure and elucidation and of synthesis have
been still are those of natural products.
The number of natural product is very large indeed which include carbohydrates,
proteins, lipids, steroids and alkaloids
CARBOHYDRATES
Carbohydrates are the most abundant of all the natural products and are widely
distributed both in plants and animal kingdom. They include cellulose, starch, glycogen,
cane sugar, lactose, fructose, etc. The name “carbohydrate” is an old name and
originates from the fact that many of carbohydrates have the empirical formula C n(H 2O)n
corresponding to a "hydrates of carbon”, as for example arabinose C n(H 2O)n
corresponding to a “hydrates of carbon”, as for example arabinose ,C 5H 10O 5 and
glucose,
C 6H 12O 6.
Some empirical formulas do not conform to this, for example, rhamnose, C 6H
O
,and
mannitol
12 5
C 6H 14O 6 C n(H 2O)n corresponding to a “hydrates of carbon”, as for example arabinose, C
5H 10O 5 and glucose, C 6H 12O 6.
.
New Definattion
Polyhydroxy aldehydes or ketones or substances which yields such compounds on
hydrolysis.
Carbonate are mainly formed in plants from CO2 and H 2O and the pigment
chlorophyll as catalyst in presence of light .The relatively simple molecules polymerize to
give cellulose or starch which constitute the framework of plants and serve as food for
new growing plants. Starch is major nutrient for animals
CO2 + H 2O +Sunlight C 6H 12O6 + 6O2
C 6H 12O6 Polymerizes to cellulose or Starch
Classification
The carbohydrates are classified as mono-sacharides, oligosacchahrides, and poly
saccharides, depending upon the number of simple sugar units linked together in the
molecule.
Monomeric sugars which are not hydrolyzed are called monosaccharide.
Monosaccharide are further divided into triose, tetroses, pentoses, hexoses,etc.
depending upon the number of carbon atoms in the molecule and as aldose, and,ketose
depending on whether they possess an aldehyde or ketone functional group. The latter
designations are often combined. Thus an aldopentose is a five carbon monosaccharide
having an aldehyde function while a ketohexose is six membered monosaccharide having a
keto group. Glyceraldehyde, CH 2OHCHO, which if the simplest monosaccharide is not
considered a carbohydrate because it is not polyhydroxy compound.
Monosaccharide
Triose, C3H6O3 e.g Glyceraldehyde, dihydroxy acetone
Tetroses, C 64H8O4 e.g erythrulose
Pentoses, C5H10O 5 e.g ribose, xylose, arabinose
Hexoses C 6H 12O6 e.g , glucose, fructose, galactose,
Heptose C7H14O7 e.g sedoheptulose
Oligosaccharide
These include disaccharide C 12H 22O11,e.g sucrose, maltose which yield two molecules of
monosaccharides on hydrolysis
C 12H 22O11+H 2O C 6H 12O6 +C 6H 12O6
Sucrose
Glucose Fructose
Trisaccharide
C 18H 32O16 +
H 2O
C 6H 12O6 +C 6H 12O6+C 6H 12O6
Riffinose
glucose, fructose, galactose
Tetrasaccharide
Stachyose occurs in plant kingdom as a product of partial hydrolysis of
polysaccharide. It gives four molecule of monosachharides on hydrolysis.
Pentasaccharide
Verbascose found in the roots of vervbascom thapsus is a pentasaccharide .It gives
five molecules of monosaccharides on hydrolysis.
Hexasaccharide
And so on up to plymers of twelve monosaccharides units are known
Polysaccharide
These are high molecular-weight polymers built up by repeated condensation on
monosaccharides through oxygen bridges e.g cellulose, starch and glycogens having
formula (C6H10O 5)n.. On complete hydrolysis these yield glucose e.g
(C6H10O 5) n + 2H 2O

n(C6H12O6)n
Amino Acids
Lipids
The living cell contains water, carbohydrates, proteins and other soluble solvents like
ether. These ether soluble organic substances are given the general name of
lipidsLipids constitute many, often , hetrogeneous substances and are not made up of
one building block.
lipids are therefore classified on the basis of solubilty and the products obtained upon
hydrolysis. The following classification is largely accepted
1. Triglycrides
2. Phospholipids
3. Waxes
4. Steriods
5. Terpenes
[a}Triglycrides
Are esters of glycerides of glycerol with monocarboxylic acids,triglycerids and are
more commonly referred to as fats and oils consitutes the abundant lipids
A typical example of an oil can be hydrolysed to glycerol and a mixture of carboxylic acids
Hydrolysis of fat and oils are listed below
Lauric acid CH3(CH2)10COOH found chiefly in coconut oil
Myristic acid CH3(CH2)12COOH found chiefly in coconut oil
Palmitic acid CH3(CH2)14COOH occurs in lard,beef,and mutton fat also in palm oil and
seed oil
Stearic acid CH3(CH2)16COOH occurs in lard,beef,and mutton fat.
Oleic Acid
CH3(CH2)7CH=CH(CH2 )7COOH occurs in lard, beef, and mutton fat, butter
oil, palm oil ,peanut oil, and olive oil
Animal glycerides are
(b)Phospholipids
A Typical Phospholipid is phosophatidic acid
CH2-OCOR
I
CHOCOR`
I
OH
CH 2OP <
II
OH
O
© Waxes
The esterification of carboxylic acid of high molecular weight with a monohydric alcohol
result in formation of a wax e.g,
O
//
CH3.(CH2)14COOH + CH 3.(CH2)13 OH CH3.(CH2)14CO.(CH2)13 CH 3
Palmitic acid
cety alcohol
cety palmitate
(d) Steriods.
Any of a class of natural or synthetic organic chemical compounds characterized by
a molecular structure of 17 carbon atoms arranged in four rings. In the parent structure
(named gonane and referred to as the steroid nucleus), the carbon atoms are bonded to
28 hydrogen atoms.
Steroids are important in biology, chemistry, and medicine. They include the sex
hormones, adrenal cortical hormones, bile acids, sterols, anabolic agents, and oral
contraceptives.
The steroid nucleus is three dimensional. Steroids vary from one another not
only in the nature of the attached groups but also in the configuration of the steroid
nucleus and the position of the groups. Small modifications in the molecular structures of
steroids can produce remarkable differences in their biological activities. Chemists have
isolated hundreds of steroids from plants and animals. Thousands more have been made
by treating natural steroids chemically or by synthesis.
Organic solvents are used to isolate steroids from natural sources. Sterols, the most
abundant of the steroids, are treated with an alkali and then extracted by means of
water-immiscible solvents, such as hexane or ether. Highly purified steroids can be
obtained in the laboratory by these methods. Commercially large amounts of steroids are
usually purified by repeated crystallization from solvents.
In plants and animals, steroids appear to be biosynthesized by similar reactions,
beginning with acetic acid, assisted by a type of enzyme. The isoprenoid hydrocarbon
called squalene, which occurs widely in nature, is thought to be the starting material
from which all steroids are made. Enzymatic transformation of squalene produces
lanosterol in animals and cycloartenol in plants, which yield cholesterol in both animals
and plants. Cholesterol is then converted to bile acids and steroid hormones in animals
and to steroids such as alkaloids in plants.
The commercial and laboratory synthesis of steroids usually begins with a one-ring
starting material such as quinone, upon which other rings are built. Total synthesis of
steroids has proved commercially feasible, but it is often more practical to prepare them
by modifying other steroids that are naturally abundant. Certain microbes can transform
parts of the steroid molecule, and industrial steroids are often made by a combination of
chemical and microbiological techniques.
All the sex hormones and corticosteroids, which originate in the adrenal cortex,
are derived from one of the most widely occuring steroids—namely, cholesterol.
Corticosteroids play an essential role in maintaining life through a variety of hormonal
functions that help to balance the ionic composition of the body fluids. Bile acids, a type
of steroid found in mammals, play a role in emulsifying fats during digestion.
Cholesterol, in addition to its role as a precursor of steroid hormones, is an important
component of cell membrane. Unfortunately, in some persons excess serum cholesterol
contributes to the formation of deposits on the arterial walls, which leads to
atherosclerosis.
The first therapeutic use of steroids goes back to the 18th century when
foxglove extracts were found to be beneficial for some heart conditions. The active
ingredient in these preparations, digitalis, is still used today. It is a steroid glycoside, a
molecule in which a steroid is linked to a sugar residue. Many plant steroids are cardiac
glycosides, which in large doses can be fatal and may be used by the plant to ward off
predatory insects. Some toads secrete steroid glycosides that may also act as a defense
mechanism.
Sex Hormones
Any of a group of hormones that belong to the class of chemical compounds known
as steroids. They are secreted by three “steroid glands”—the adrenal cortex, testes,
and ovaries—and during pregnancy by the placenta. All steroid hormones are derived
from cholesterol. They are transported through the bloodstream to the cells of various
target organs where they carry out the regulation of a wide range of physiological
functions.
These hormones often are classified according to the organs that synthesize them:
the adrenal steroids are so called because they are secreted by the adrenal cortex, and
the sex hormones are those produced by the ovaries and testes. This distinction is not
exclusive, however, because the adrenal cortex also secretes sex hormones, albeit to a
lesser extent than do the gonads, and the ovaries under abnormal conditions may produce
adrenal steroids.
The adrenal cortex produces the adrenocortical hormones, which consist of the
glucocorticoids and the mineralocorticoids. Glucocorticoids such as cortisol control or
influence many metabolic processes, including the formation of glucose from amino
acids and fatty acids and the deposition of glycogen in the liver. Glucocorticoids also
help to maintain normal blood pressure, and their anti-inflammatory and
immunosuppressive actions have rendered them useful in treating rheumatoid
arthritis and preventing the rejection of transplanted organs. Mineralocorticoids such
as aldosterone help maintain the balance between water and salts in the body,
predominantly exerting their effects within the kidney.
Male sex hormones
The androgens are the male sex hormones. The principal androgen, testosterone,
is produced primarily by the testes and in lesser amounts by the adrenal cortex and (in
women) by the ovaries. Androgens are primarily responsible for the development and
maintenance of reproductive function and stimulation of the secondary sex
characteristics in the male. Androgens also have an anabolic (synthesizing and
constructive, rather than degradative) function in stimulating the production of
skeletal muscles and bone as well as red blood cells. To enhance the anabolic activity
of androgens without increasing their masculinizing ability, anabolic steroids were
developed. Though originally intended to combat diseases marked by wasting, these
synthetic hormones have been abused by individuals desiring to increase their muscle
mass, such as athletes seeking to gain a competitive advantage. Overdosing has been
linked to serious side effects, including infertility and coronary heart disease.
Female sex hormones.
Estrogens are one of the two types of female sex hormones. They are secreted
mainly by the ovaries and in smaller amounts by the adrenal glands and (in men) by the
testes. Estradiol is the most potent of the estrogens. Functioning similarly to androgens,
the estrogens promote the development of the primary and secondary female sex
characteristics; they also stimulate linear growth and skeletal maturation. In other
mammals these hormones have been shown to precipitate estrus (heat). The ovarian
production of estrogen plummets during menopause.
Progestins, the most important of which is progesterone, are the other type of
female sex hormone and are named for their role in maintaining pregnancy (progestation). Estrogens and progestins are secreted cyclically during menstruation. During
the menstrual cycle, the ruptured ovarian follicle (the corpus luteum) of the ovary
produces progesterone, which renders the uterine lining receptive to the implantation of
a fertilized ovum. Should this occur, the placenta becomes the main source of
progesterone, without which the pregnancy would terminate. As pregnancy progresses,
placental production of progesterone increases, and these high doses suppress
ovulation, preventing a second conception. The contraceptive quality of progesterone
led to the development of structurally modified progestins and estrogens—the oral
contraceptives known as birth-control pills, used by women to prevent unwanted
pregnancy.
Corticosteroids and their synthetic analogues, such as prednisone and
dexamethasone, are used therapeutically to control rheumatism and other inflammatory
ailments. Anabolic steroids—which increase constructive metabolism—are sometimes
administered to postoperative and geriatric patients to promote muscle growth and
tissue regeneration. In recent years, a growing number of amateur and professional
athletes have made use of synthetic analogues of testosterone to accelerate muscular
development and to improve strength. Medical researchers have determined that anabolic
steroids can have harmful effects, particularly in young people who are still developing
physically. Continued and prolonged use may lead to heart disease, sexual and
reproductive disorders, immune deficiencies, liver damage, stunted growth (in
teenagers and young adults), and aggressive, violent behaviour.
The most widely employed steroid drugs, however, are undoubtedly the oral
contraceptives, which were introduced in the early 1960s. These synthetic materials,
which act by suppressing ovulation, are made chiefly from diosgenin, a plant steroid
obtained from wild yams.
(e) Terpenes
Terrpenes are widespread in nature, mainly in plants as constituents of essential
oils. Many terpenes are hydrocarbons, but oxygen-containing compounds such as alcohols,
aldehydes or ketones (terpenoids) or preferably Isoterpnoids are also found. Their
building block is the hydrocarbon isoprene, CH2=C (CH3)-CH=CH2 (isoprene rule, Wallach
1887). Terpene hydrocarbons therefore have molecular formulas (C5H8) n; they are
classified according to the number of isoprene units:
number of isoprene units
monoterpenes
2
sesquiterpenes 3
diterpenes
4
triterpenes
6
tetraterpenes
8
Examples of monoterpenes are: pinene, nerol, citral, camphor, menthol, limonene.
Examples of sesquiterpenes are: nerolidol, farnesol.
Examples of diterpenes are: phytol, vitamin A1.
Squalene is an example of a triterpene, and carotene (provitamin A1) is a tetraterpene
Many of the isoprenoids possess carbon skeletons that may be regarded as built up
from isoprene units linked “head to tail”; that is, carbon atom 1 of one unit is bonded to
carbon atom 4 of the next.
Formation of additional bonds in a variety of ways leads to monocyclic, bicyclic, and
further subclasses in which one, two, or larger numbers of rings are present. -Myrcene,
an acyclic monoterpene; limonene, a monocyclic monoterpene; -pinene, a bicyclic
monoterpene; and vitamin A, an oxygenated monocyclic diterpene, exemplify this further
classification; the dotted lines in the structural formulas indicate the division of the
carbon skeletons into isoprene units.
Tail-to-tail coupling
The structures of most triterpenes and tetraterpenes show that they were formed
by establishment of a tail-to-tail (carbon 4 to carbon 4) bond between two smaller units:
in the structural formula of the important triterpene hydrocarbon squalene, for example,
the arrow indicates the bond uniting two sesquiterpene portions.
The head-to-tail coupling of isosprenoid units in biosynthesis logically follows from
expected enzymic reaction patterns of the pyrophosphate units as shown below in the
section Biosynthesis. Tail-to-tail coupling does not appear to follow expected reaction
patterns. Squalene, which has the most notable example of tail-to-tail coupling, is formed
by the joining of two equivalents of farnesyl pyrophosphate. In the 1960s the British
chemist John W. Cornforth showed that omitting a necessary reductant in the enzyme
system that promotes the formation of squalene causes an unusual compound containing a
three-membered ring, called presqualene pyrophosphate, to accumulate. (OPP represents
the pyrophosphate group.)
Addition of the reductant permits conversion of presqualene to squalene. This
compound was shown to be formed by a series of bond-forming steps and bond shifts.
Reduction and ring cleavage produces the tail-to-tail linked product. Later work by the
American chemist Charles Dale Poulter has shown that intermediates with threemembered rings also are involved in the formation of isoprenoids in which the units are
joined by linkages that are neither head-to-tail nor tail-to-tail, such as botrycoccene, a
plant isoprenoid that has a connection of carbon 2 to carbon 4.
FUNCTIONS OF THE ENDOCRINE SYSTEM
Adaptive responses to stress
Throughout the life of the organism endocrine influences are at play to enhance
the ability of the body to respond to internal and external stressful stimuli. These changes
allow not only the individual organism but also the species to survive. Early studies by
Cannon led him to the thesis that acutely threatened animals respond with multiple
physical changes, including endocrine changes, that prepare them to react or retreat, a
process known as “the fight or flight reaction.”
Adaptive responses for more prolonged stresses also occur. For example, in states
of malnutrition typical of the self-induced semi-starvation condition called anorexia
nervosa, there is reduced secretion of thyroid hormones (hormones that generally
stimulate metabolic processes of the body), leading to a lower metabolic rate. This
change reduces the rate of the consumption of the body's fuel, and thus reduces the rate
of consumption of the remaining energy stores. This change has obvious survival value;
death from starvation is deferred.
Parenting behaviour
The endocrine system, particularly the hypothalamus, the anterior pituitary, and
the gonads, is intimately involved in reproductive behaviour by providing physical, visual,
and olfactory (pheromonal) signals that arouse the sexual interest of the male and the
receptivity of the female. Furthermore, there are powerful endocrine influences on
parental behaviour in all species, probably including humans.
Traditional endocrinology
Because endocrinology involves an actively expanding body of knowledge, its
borders remain difficult to define. The traditional core of an endocrine system, however,
consists of
(1) an endocrine gland,
(2) its hormonal secretion,
(3) a responding tissue containing a specific receptor to which the hormone will
become bound, and
(4) the action that results after the hormone becomes bound, termed the
postreceptor response.
Each endocrine gland consists of a group of specialized cells that have a common
origin in the developing embryo. Many endocrine glands are derived from cells that arise
in the embryonic digestive system (e.g., the thyroid and pancreas) or from cells that
migrate from the embryonic nervous system (e.g., the parathyroid and adrenal medulla).
Still others arise from a region of the embryo known as the urogenital ridge (ovary, testis,
and adrenal cortex). The pituitary gland is derived from cells that originate in both the
nervous system and the digestive tract.
Each endocrine gland has a rich supply of blood, which is directly related to its role
in synthesizing and secreting hormones. Many endocrine glands secrete more than one
hormone. Some organs function both as exocrine glands and as endocrine glands. The
pancreas is the best-known example.
In addition to the more traditional endocrine cells described above, specially
modified nerve cells within the nervous system secrete important hormones into the
blood. These special nerve cells are called neurosecretory cells, and their secretions are
termed neurohormones to distinguish them from the hormones produced by traditional
endocrine cells. The areas of the nervous system that produce neurohormones also have a
rich vascular supply, and the neurohormones are either released into the blood or stored
in adjacent blood-rich areas (called neurohemal organs) until needed.
Most hormones are one of two types: proteins (including peptides and modified
amino acids) or steroids.
The majority of hormones are the protein type. They are highly soluble in
water and can be transported readily through the blood. The protein hormones, when
initially synthesized within the cell, are contained within larger, biologically inert
molecules called prohormones. The inactive portion of the prohormone is split away so
that one or more active fragments that are released from the cell circulate through
the blood. A smaller number of hormones are the water-soluble, fatty acid steroid
hormones, all of which are synthesized from the precursor molecule cholesterol. These
lipid hormones are transported through the blood by first being bound to proteins in
the blood.
All body tissues that respond to a specific hormone contain specially shaped
molecular configurations called receptors. These receptors are found on the surface of
target cells, in the case of protein and peptide hormones, or within the cytoplasm, in
the case of steroids and modified amino acid hormones. Each receptor has a strong,
highly specific affinity (attraction) for a particular hormone.
This arrangement permits a specific hormone to have an effect only on those
tissues for which it is “targeted,” namely, those that are equipped with specific binding
receptors. Usually, one segment of the hormone molecule exhibits a strong chemical
affinity for the receptor while another area is responsible for initiating its specific action.
Thus, hormonal actions are not general throughout the body but rather are aimed at
specific target tissues.
The hormone-receptor complex that is formed then activates a chain of specific
chemical responses within the cells of the target tissue to complete the hormonal action.
This action may be the result of the activation of enzymes within the target cell, of the
interactions of the hormone-receptor complex with the nucleus of the cell, and
consequent stimulation of new protein synthesis, or of a combination of both. It may even
result in secretion of another hormone.
General features
THE NATURE OF ENDOCRINE REGULATION
Endocrine gland secretion is not a haphazard process; it is subject to precise,
intricate control at several levels so that its effect may be integrated with those of
the nervous system and the immune system. The simplest level of control resides at the
endocrine gland itself.
Characteristically, the signal for an endocrine gland to release
more or less of its hormone is the level of some substance, either a hormone that
influences the action of a gland (called a tropic hormone), a biochemical product such as
glucose, or a biologically important element such as potassium or calcium. Because the
endocrine gland has a rich supply of blood, it is able to detect changes in the level of this
regulating substance.
Some endocrine glands, for example the parathyroid glands located in the neck,
are controlled largely by a simple negative feedback mechanism. Parathyroid hormone,
known as parathormone, acts on its major target organ, bone, and other tissues to
transport calcium into the blood, raising the serum calcium level. Elevated serum
calcium levels inhibit the secretion of parathormone by the parathyroid glands. Thus,
if for any reason serum calcium levels become elevated, parathormone secretion is
blocked and calcium is not secreted into the serum from bone; the serum calcium level
then falls back into the normal range. If, on the other hand, the serum calcium level
should fall, the parathyroids are no longer inhibited from releasing parathormone and
parathyroid gland activity is stimulated. The increased circulating levels of
parathormone stimulate increased dissolution of bone, releasing calcium. Thus,
calcium enters into the serum from bone, and the serum calcium concentration rises until
it reaches a normal level.
In this fashion, in individuals with normal parathyroid glands, serum calcium levels
are maintained within a narrow range even in the face of large changes in calcium intake
or excessive losses of calcium from the body.
Control of the hormonal secretions of a number of other endocrine glands is more
complex because the glands are, themselves, target organs of a regulatory system
called the hypothalamic-pituitary-target organ axis. Glands of this type include the
thyroid, the adrenal cortex, and the gonads (testes and ovaries).
The major mechanism involves interconnecting negative feedback loops, each
similar to that described above, which involve the hypothalamus (a structure located at
the base of the brain and above the pituitary), the anterior pituitary, and the target
organ. The hypothalamus stimulates the pituitary, through neurohormones, to secrete
pituitary hormones, which affect any of a number of target organs. The hypothalamicpituitary-target organ axis is one of the more elegant devices to be found in nature. The
target gland secretes its hormone (target gland hormone), which combines with the
receptors of a secondary target tissue and is then inactivated. This continues until the
concentration of target gland hormone in the blood exceeds the amount necessary to bind
all of the tissue receptors. The effect of the target gland hormone on the secondary
target tissue is quantitative; that is, within limits, the greater the amount of target
gland hormone bound to receptors in the secondary target tissue, the greater the
secondary target tissue cell response.
The target gland hormone also binds to specific receptors in the anterior pituitary
to inhibit the secretion of pituitary-stimulating hormone (the hormone that stimulates the
target gland to secrete more target gland hormone). As the concentration of the target
gland hormone in the blood rises, there is an appropriate decrease in the production of
pituitary-stimulating hormone. Thus, there will be less activation of the target gland to
produce its hormone. The end result of this feedback mechanism is that the high level of
target hormone circulating in the bloodstream falls back to normal.
Conversely, as more target gland hormone is bound to receptors in the secondary
target tissue, the levels of target gland hormone circulating in the bloodstream falls. The
overall inhibitory effects of target gland hormone on the pituitary gland then is reduced.
Low levels of target gland hormone thus stimulate production of more pituitarystimulating hormone, which in turn stimulates the secretion of target gland hormone by
the target gland, until the concentration of target gland hormone in the blood increases
to a normal level.
A second, similar negative feedback loop is superimposed on the first. The target
gland hormone binds to nerve cells in the hypothalamus, which inhibit the secretion of
specific hypothalamic-releasing hormones (neurohormones) that stimulate the secretion
of pituitary hormone (an important element in the previous negative feedback loop). The
concentrations of hypothalamic-releasing hormones within a set of veins that connects
the hypothalamus and the pituitary gland (the hypophyseal-portal circulation) is reduced.
The importance of this second loop lies in the fact that the nerve cells of the
hypothalamus communicate with nervous influences that extend down from the brain,
including the cerebral cortex (the centre for higher mental functions, movement,
perceptions, etc.), thus permitting the endocrine system to respond to physical and
emotional stresses. The mechanism involves the interruption of the primary feedback loop
so that the concentrations of hormones in the blood can be increased or decreased
appropriately in response to environmental stresses perceived by the nervous system (see
below The hypothalamus). If this were not available, all blood hormones would be locked
in at normal concentrations, even at times when it would be important to the body for
these hormones to diverge from normal levels. Similarly, appropriate endocrinologic
responses can be achieved from stimuli resulting from signals generated through the
immune system to threats (such as bacterial invasion) from within the organism.
Finally, a third short loop directly inhibits the release of a specific hypothalamicreleasing hormone by a pituitary hormone. In this fashion, concentrations of pituitary,
thyroid, adrenal cortex, and gonadal hormones in the blood are maintained at normal,
homeostatic levels, but, when necessary, the hormonal levels may be altered
dramatically to meet changing circumstances of the internal or external environment.
This traditional view of the mechanisms that control endocrine secretion has been
modified by evidence pointing to important supplemental control mechanisms. When, as
is usually the case, more than one cell type is found within a single endocrine gland, the
hormones secreted by one cell may exert a direct modulating effect upon the secretions
of its immediate neighbour of a different cell type. This form of control is known as
paracrine function. Similarly, the secretions of one endocrine cell may affect the activity
of a neighbour cell of identical type, an activity known as autocrine function. Thus,
endocrine cell activity may be modulated directly from within the endocrine gland itself
without the need for hormones to enter the general circulation.
Excluding from the definition of a hormone the requirement that it act at a site
remote from the secreting endocrine cell allows additional classes of bioactive materials
to be considered as hormones. Neurotransmitters, a group of chemical compounds of
variable composition, are secreted at all synapses (junctions between nerve cells over
which nervous impulses must pass). They facilitate or inhibit the transmission of neural
impulses and have given rise to the hybrid science of neuroendocrinology (the branch of
medicine that studies the interaction of the nervous system and the endocrine system).
A second group of novel bioactive substances are called the prostaglandins,
a complex group of fatty acids that are formed and secreted by many tissues. They
mediate important biological effects in almost every organ system of the body.
Another group of substances with hormonelike actions is called growth factors.
These are substances that stimulate the growth of specific target tissue cells. They are
distinct from the usual members of the endocrine family of growth hormones in that they
were identified only after it was noted that target cells grown outside the organism in
tissue culture could be stimulated to grow and reproduce by gland or tissue extracts
chemically distinct from any known growth hormone.
Still another area of hormonal classification that has come under intensive investigation is
the effect of endocrines on animal behaviour. While simple, direct hormonal effects on
human behaviour are difficult to document because of the complexities of human
motivation, there are many convincing demonstrations of hormone-mediated behaviour in
other life forms.
A special case is that of the
pheromone, a substance generated by an organism that influences, by its odour, the
behaviour of another organism of the same species. An often-quoted example is the
musky scent of the females of many species, which provokes sexual excitation in the
male. Such devices have obvious adaptive value for species survival.
Akaloids
A class of naturally occurring organic nitrogen-containing bases. Alkaloids have
diverse and important physiological effects on humans and other animals. Well-known
alkaloids include morphine, strychnine, quinine, ephedrine, and nicotine.
Alkaloids are found primarily in plants and are especially common in certain
families of flowering plants. More than 3,000 different types of alkaloids have been
identified in a total of more than 4,000 plant species. In general, a given species contains
only a few kinds of alkaloids, though both the opium poppy (Papaver somniferum) and the
ergot fungus (Claviceps) each contain about 30 different types. Certain plant families are
particularly rich in alkaloids; all plants of the poppy family (Papaveraceae) are thought to
contain them, for example. The Ranunculaceae (buttercups), Solanaceae (nightshades),
and Amaryllidaceae (amaryllis) are other prominent alkaloid-containing families. A few
alkaloids have been found in animal species, such as the New World beaver (Castor
canadensis) and poison-dart frogs (Phyllobates). Ergot and a few other fungi also produce
them.
The function of alkaloids in plants is not yet understood. It has been suggested that
they are simply waste products of plants' metabolic processes, but evidence suggests that
they may serve specific biological functions. In some plants, the concentration of
alkaloids increases just prior to seed formation and then drops off when the seed is
ripe, suggesting that alkaloids may play a role in this process. Alkaloids may also protect
some plants from destruction by certain insect species.
The chemical structures of alkaloids are extremely variable. Generally, an alkaloid
contains at least one nitrogen atom in an amine-type structure—i.e., one derived from
ammonia by replacing hydrogen atoms with hydrogen-carbon groups called hydrocarbons.
This or another nitrogen atom can be active as a base in acid-base reactions. The name
alkaloid (“alkali-like”) was originally applied to the substances because, like the inorganic
alkalis, they react with acids to form salts. Most alkaloids have one or more of their
nitrogen atoms as part of a ring of atoms, frequently called a cyclic system. Alkaloid
names generally end in the suffix -ine, a reference to their chemical classification as
amines. In their pure form most alkaloids are colourless, nonvolatile, crystalline solids.
They also tend to have a bitter taste.
Interest in the alkaloids stems from the wide variety of physiological effects (both
wanted and unwanted) they produce in humans and other animals. Their use dates back
to ancient civilizations, but scientific study of the chemicals had to await the growth of
organic chemistry, for not until simple organic bases were understood could the intricate
structure of the alkaloids be unraveled. The first alkaloid to be isolated and crystallized
was the potent active constituent of the opium poppy, morphine, in 1805–06.
Alkaloids are often classified on the basis of their chemical structure. For example,
those alkaloids that contain a ring system called indole are known as indole alkaloids. On
this basis, the principal classes of alkaloids are the pyrrolidines, pyridines, tropanes,
pyrrolizidines, isoquinolines, indoles, quinolines, and the terpenoids and steroids.
Alternatively, alkaloids can be classified according to the biological system in
which they occur. For example, the opium alkaloids occur in the opium poppy (Papaver
somniferum). This dual classification system actually produces little confusion because
there is a rough correlation between the chemical types of alkaloids and their biological
distribution.
The medicinal properties of alkaloids are quite diverse. Morphine is a powerful
narcotic used for the relief of pain, though its addictive properties limit its usefulness.
Codeine, the methyl ether derivative of morphine found in the opium poppy, is an
excellent analgesic that is relatively nonaddictive.
Certain alkaloids act as cardiac or respiratory stimulants. Quinidine, which is
obtained from plants of the genus Cinchona, is used to treat arrhythmias, or irregular
rhythms of the heartbeat.
Many alkaloids affect respiration, but in a complicated manner such that severe
respiratory depression may follow stimulation. The drug lobeline (from Lobelia inflata) is
safer in this respect and is therefore clinically useful. Ergonovine (from the fungus
Claviceps purpurea) and ephedrine (from Ephedra species) act as blood-vessel
constrictors. Ergonovine is used to reduce uterine hemorrhage after childbirth, and
ephedrine is used to relieve the discomfort of common colds, sinusitis, hay fever, and
bronchial asthma.
Many alkaloids possess local anesthetic properties, though clinically they are
seldom used for this purpose. Cocaine (from Erythroxylon coca) is a very potent local
anesthetic. Quinine (from Cinchona species) is a powerful antimalarial agent that was
formerly the drug of choice for treating that disease, though it has been largely replaced
by less toxic and more effective synthetic drugs. The alkaloid tubocurarine is the active
ingredient in the South American arrow poison, curare (obtained from Chondrodendron
tomentosum), and is used as a muscle relaxant in surgery.
Two alkaloids, vincristine and vinblastine (from Vinca rosea), are widely used as
chemotherapeutic agents in the treatment of many types of cancer.
Nicotine obtained from the tobacco plant (Nicotiana tabacum) is the principal
alkaloid and chief addictive ingredient of the tobacco smoked in cigarettes, cigars, and
pipes.
Some alkaloids are illicit
drugs and poisons. These include the hallucinogenic drugs mescaline (from Anhalonium
species) and psilocybin (from Psilocybe mexicana). Synthetic derivatives of the alkaloids
morphine and lysergic acid (from C. purpurea) produce heroin and LSD, respectively.
The alkaloid coniine is the active component of the
poison hemlock (Conium maculatum). Strychnine (from Strychnos species) is another
powerful poison.
Special methods have been developed for isolating commercially useful alkaloids.
In most cases, plant tissue is processed to obtain aqueous solutions of the alkaloids. The
alkaloids are then recovered from the solution by a process called extraction, which
involves dissolving some components of the mixture with reagents. Different alkaloids
must then be separated and purified from the mixture.
Chromatography may be
used to take advantage of the different degrees of adsorption of the various alkaloids on
solid material such as alumina or silica. Alkaloids in crystalline form may be obtained
using certain solvents.
Narcotic analgesic drug used in medicine in the
form of its hydrochloride, sulfate, acetate, and tartrate salts. Morphine was isolated from
opium by the German chemist F.W.A. Sertürner in 1806. In its power to reduce the level
of physical distress, morphine is among the most important naturally occurring
compounds, being of use in the treatment of pain caused by cancer and in cases where
other analgesics have failed. It also has a calming effect that protects the system against
exhaustion in traumatic shock, internal hemorrhage, congestive heart failure, and
debilitated conditions (as certain forms of typhoid fever). It is most frequently
administered by injection to ensure rapid action, but it is also effective when given
orally.
Morphine produces a relaxed, drowsy state and many side effects that result from
the depression of the respiratory, circulatory, and gastrointestinal systems. It also is an
emetic and a general depressant. The most serious drawback to the drug is its
addictiveness.
Morphine, an opium alkaloid, can be converted into heroin, which shows a
considerably stronger euphoric effect and is so powerfully addictive that its
manufacture is legally prohibited. Other derivatives of morphine include the analgesics
methylmorphine (codeine), ethylmorphine, dihydrocodeinone, and dihydromorphinone
and the emetic apomorphine.
The structure of morphine proposed in the 1920s by J.M. Gulland and R. Robinson
was confirmed in 1952 by its total synthesis, accomplished by M. Gates and G. Tschudi.
Synthetic organic chemistry also has provided a number of compounds (as meperidine,
methadone, and pentazocine) that have in part supplanted morphine in medical use.
Morphine is extracted from the dried milky exudate of the unripe seed capsule of
the opium poppy (Papaver somniferum). It occurs as colourless crystals or a white
crystalline powder.
Cocaine
white, crystalline alkaloid that is obtained from the leaves of the coca plant
(Erythroxylum coca), a bush commonly found growing wild in Peru, Bolivia, and Ecuador
and cultivated in many other countries. The chemical formula of cocaine is C 17H21NO4.
Cocaine acts as an anesthetic because it interrupts the conduction of impulses in nerves,
especially those in the mucous membranes of the eye, nose, and throat. More
importantly, cocaine when ingested in small amounts produces feelings of well-being and
euphoria, along with a decreased appetite, relief from fatigue, and increased mental
alertness. When taken in larger amounts and upon prolonged and repeated use, cocaine
can produce depression, anxiety, irritability, sleep problems, chronic fatigue, mental
confusion, paranoia, and convulsions that can cause death.
For centuries the Indians of Peru and Bolivia have chewed coca leaves mixed with
pellets of limestone or plant ashes for pleasure or in order to withstand strenuous working
conditions, hunger, and thirst. In other cultures the active alkaloid is chemically
extracted from coca leaves and is converted into the hydrochloric salt of cocaine, cocaine
hydrochloride. This fine white powder is sniffed through a hollow tube and is readily
absorbed into the bloodstream through the nasal mucous membranes. Cocaine is an
irritant, however, and acts to constrict blood vessels, causing a chronic runny nose or, in
severe cases, ulcerations in the nasal cavity. The euphoric effects of sniffing cocaine are
relatively transitory and wear off after about 30 minutes. Cocaine is habit-forming and
may also be physically addicting. Cocaine is also injected in solution or smoked in a
chemically treated form known as freebase; either of these methods produces a markedly
more compulsive use of the drug. In the 1980s a new preparation of cocaine appeared,
called crack; the smoking of crack produces an even more intense and even more shortlived euphoria that is extremely addicting. This form of cocaine consumption is also the
one most detrimental to health. Another smokable and highly addictive form is cocaine
paste, which is an intermediate stage in the processing of coca leaves into cocaine.
The prolonged or compulsive use of cocaine in any of its purified forms can cause
severe personality disturbances, inability to sleep, and loss of appetite. A toxic psychosis
can develop involving paranoid delusions and disturbing tactile hallucinations in which the
user feels insects crawling under his skin. Cocaine abuse, which had been a marginal drug
problem throughout much of the 20th century, grew alarmingly in the late 20th century in
several countries, and cocaine has become responsible for a markedly in
Quinine
The most important alkaloid of cinchona bark, used chiefly in the treatment of
malaria. During the 300 years between its introduction into Western medicine and World
War I, quinine was the only effective remedy for malaria. As a specific treatment for this
disease, quinine has benefitted more people than any other drug used thus far to combat
infectious diseases. The treatment of malaria with quinine marked the first successful use
of a chemical compound in combatting an infectious disease.
Like the other cinchona alkaloids, quinine is a large and complex molecule, and its
total laboratory synthesis in 1944 is one of the classical achievements of synthetic organic
chemistry, although commercial synthesis of quinine is not economically feasible.
Quinine acts by interfering with the growth and reproduction of the malarial
parasites (Plasmodium species) inhabiting the red cells of the blood; it probably prevents
the parasites from oxidizing glucose, their chief source of energy. Administration of
quinine dramatically improves the condition of a person suffering from malaria; the
parasites promptly disappear from the blood, and the symptoms of the disease are quickly
alleviated. When quinine treatment is terminated, however, many recovered patients
suffer another attack of malaria several weeks later. This recurrence stems from the
failure of quinine to kill the malarial parasites in cells of the body other than the red
blood cells. These parasites persist and, after a time, reinvade the red blood cells and
precipitate the second malarial attack, or relapse.
Because quinine fails to produce a complete cure of malaria, better antimalarial
drugs have long been sought. Research during World War II produced a number of
antimalarial drugs that almost completely replaced quinine. Some of them, such as
chloroquine and chloroguanide, are more effective than quinine in suppressing the
growth of the blood forms of the malarial parasite; others, such as primaquine and
pyrimethamine, act upon both the blood and tissue stages of the parasite, thus producing
complete cures and preventing relapses. All of the newer antimalarials, unlike quinine,
may be completely synthesized on a commercial scale.
During the 1960s several strains of the malarial parasite Plasmodium falciparum
developed resistance to the synthetic drugs, particularly the highly valued chloroquine.
The parasite remained sensitive, however, to quinine, which had to be reinstated in
various parts of the world as the drug of choice despite the side effects that sometimes
occur when the necessarily large doses of quinine are given.
In addition to its specific use in malaria, quinine is sometimes used as a nonspecific
remedy for fever and pain. It reduces fever probably by dilating the small vessels of the
skin; its analgesic (pain-relieving) effect may result from depression of certain centres in
the central nervous system. Prolonged administration of quinine may produce toxic
symptoms such as deafness, disturbances in vision, skin rashes, and digestive upsets.
Some experts believe that patients who undergo quinine treatment may be predisposed to
develop blackwater fever, a little understood complication of malaria marked by rapid
and severe anemia and the appearance of hemoglobin (the oxygen-carrying blood
pigment) in the urine. creased proportion of drug-induced deaths.
mescaline
also called -3,4,5-trimethoxyphenethylamine
naturally occurring alkaloid, the active principle contained in the flowering heads of the
peyote (q.v.) cactus (species Lophophora williamsii) of Mexico and the southwestern
United States, that has been used as a drug to induce hallucination. The mescaline
molecule is related structurally to two hormones secreted by the adrenal glands,
adrenaline and noradrenaline; both are catecholamine compounds that take part in the
transmission of nerve impulses. Mescaline was isolated as the active principle of peyote in
1896, and its structural resemblance to adrenaline was recognized by 1919.
In experiments mescaline requires 2 to 3 hours for onset of action, and its effects
sometimes last for more than 12 hours. The hallucinatory effects vary greatly among
individuals and even for a particular individual from one drug session to the next. The
variations seem to reflect such factors as the mood and personality of the subject and the
setting in which the drug is administered. Hallucinations are usually visual, less often
auditory. Side effects include nausea and vomiting. Mescaline is prepared from the peyote
cactus by extraction and purification, but it can be synthesized