BIOSYNTHESIS OF ALKALOIDS
Alkaloids are naturally occurring organic
nitrogen-containing bases. They are secondary metabolites containing nitrogen
moiety usually heterocylic in nature. The nitrogen is usually derived from an
amino acid commonly; phenylalanine, tyrosine, tryptophan, histidine, ornithine
and anthranilic acid. Alkaloids are found primarily in plants and are
especially common in certain families of flowering plants and also fungi though
a rare source. However, they are an important source of allopathic and
homeopathic medicine because of toxicity and controlled dosage.
Some of the various types of alkaloids include;Ornithine derived alkaloids
As shown below; the amino acid, its decarboxylation
product,putrescine and proline constitute the basic unit of the tropane, ergotamine, nicotine, necine and
stachydrine groups of alkaloids.
Pharmaceutically the tropane group is important.Tropane
alkaloids are derived from L-ornithine. The principal alkaloid of medicinal
interest in this group are hyoscyamine that is more stable racemate atropine,
and hyoscine.T He compounds are esters and are hydrolysed by heating at 60C
with baryta water; atropine yields tropic acid and tropine; hyoscine gives
tropic acid and oscine formed by enzymatic hydrolysis but the chemical
treatment converts it to the more stable geometric isomer.The Tropane class of
alkaloids found in solanaceae contains anticholinergic drugs hyoscyamine
(racemic mixture is called atropine) and scopolamine.
Lysine derived
alkaloids
.Lysine and its associated compounds give rise to a number
of alkaloids, some of which are analogues to the ornithine group.The lycopodium
alkaloids are also derived from lysine. Although in some cases, such as the
quinolizidonejupinalkaloids ,lysine is incorporated via a symmetrical precursor
eg. Cadaverine.
Phenylalanine-tyrosine-
and dihyroxyphenylalanine-derived alkaloids
TRYPTOPHAN DERIVED
ALKALOIDS
Purine alkaloid
biosynthesis
They are derived from purine nucleotides. Members of this
class include theobromine, caffeine.
Abbreviations: CS, caffeine synthase; DXMT, 1,
7-dimethylxanthosine methyltransferase; MXMT, 7-methylxanthine
methyltransferase; TS, theobromine synthase, XMT, xanthosine
7-N-methyltransferase.
BIOSYNTHESIS OF GLYCOSIDES
A glycoside is an organic compound, usually of plant origin,
that is composed of a sugar portion linked to a non-sugar moiety,Sugar
portion-Glycone,Non-sugar portion- Aglycone / Genin,Linkage between sugar and
non-sugar is usually an “oxygen linkage”
Metabolic process of glycoside formation consists of two
parts. The first part involves biosynthesis of aglycone and the second
metabolic pathway involving coupling of aglycone with sugar moiety.
The synthesis of glycosides in plant cells involves
interaction of a nucleotide glycoside, UDP-glucose with alcoholic or phenolic
group of a second compound Aglycone leading to the formation of O-glycosides as
shown below.
Glucose
salicyl alcohol
salicin
The other glycosides occur in nature in which the linkage is
through carbon (C-glycosides), nitrogen (N-glycosides) or sulphur
(S-glycosides).
Glycoside formation involves transfer of uridylyl group from
UTP to sugar -1- phosphate and enzyme catalyzing this reaction is uridylyl
transferases.
1)
UTP + sugar-1-phosphate UDP-sugar + PP1
2)
UDP + sugar + aglyconeGlycoside UDP
2nd reaction involves transfer of sugar from UDP
to aglycone moiety resulting in formation of a glycoside and the enzyme
catalyzing the reaction is glycosyl transferases.
Sugars present in glycosides may be monosaccharides,
rhamnose, glucose and fucose or deoxysugars such as digitoxose or cymarose as
in cardiac glycosides. Since sugars exist either in the α- and β- forms, all
natural glycosides are of the β- type.
Cardiac glycosides
The aglycones of cardioactive
glycosides are steroidal in nature. The knowledge of steroidal biosynthesis is
derived from studies of cholesterol production through Acetate → Mevalonate →
Isopentenyl pyrophosphate → squalene pathway. TheAglycone of the cardiac
glycosides are derived from mevalonic acid but the final molecules arise from a
condensation of a C21 steroid with a C2 unit (the source
of C-22 and C-23). Bufadienolides are condensation products of a C21
steroid and a C3 unit. Biosynthesis of cholesterol involves
cyclization of aliphatic triterpene-squalene. The scheme for biogenesis of some
of the aglycones is as shown below
Cyanogenic glycosides
Cyanogenic glycosides are produced from a range of amino
acids by a common pathway. The main amino acids utilized in the biosynthesis of
Cyanogenic glycosides are Phenylalanine e.g. (prunasin, amygdalin), tyrosine
(e.g. dhurrin from sorghum), valine (e.g. linamarin from flax). The amino acids
used are derived from shikimate pathway.
Flavonoid glycosides
Flavonoids are derived from both the acetate and shikimate
pathway.
The triketide starter unit undergoes cyclization by the
enzyme chalcone synthase to generate the chalcone group of flavonoids.
Cyclization can then occur to give a pyranone ring containing flavanone
nucleus, which can either have the C2-C3 bond oxidized (unsaturated) to give
the flavones or be hydroxylated at position C3 of the pyranone ring to give the
flavanonol group of flavonoids. The flavanonols may then be further oxidized to
yield the anthocyanins, which contribute to the brilliant blues of flowers and
the dark colour of red wine.
References
1. Allen
RS, Millgate AG, Chitty JA, Thisleton J, Miller JA, et al. 2004.
RNAi-mediatedreplacement of morphine with the nonnarcotic alkaloid reticuline
in opium poppy. Nat.Biotechnol. 22:1559–66
2. W.C.
Evans, Trease and Evans Pharmacognosy, 15th edition copyright 2008,
Saunders pg. 135-150, 214-333.
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