Alkaloid

질소 함유 식물성분으로 질소 함유 식물성분으로 Biogenic AmineBiogenic Amine 을 을 제외한 것임제외한 것임 ..

아미노산의 최종 대사 산물로 아미노산의 최종 대사 산물로 Polyketide, PepPolyketide, Peptide, Terpenoid tide, Terpenoid 등과 함께 생합성 됨등과 함께 생합성 됨 ..

주로 염기성이나 중성 또는 약산성의 주로 염기성이나 중성 또는 약산성의 AlkaloidAlkaloid도 있음도 있음 ..

대부분 강한 생리 활성이 있으며대부분 강한 생리 활성이 있으며 , , 식물의 식물의 방어 물질 또는 최종 대사산물로 추정방어 물질 또는 최종 대사산물로 추정 ..

Biosynthesis of Amino Acid

식물은 20개의 필수 아미노산을스스로 생합성함

Amino Acid Biosynthesis

Nitrogen Fixation is the process by which atmospNitrogen Fixation is the process by which atmospheric nitrogen (Nheric nitrogen (N22) is captured by certain organis) is captured by certain organis

ms and converted into NHms and converted into NH33, a form of nitrogen tha, a form of nitrogen tha

t can be used by all organisms.t can be used by all organisms. Just as carbon fixation can be performed by only Just as carbon fixation can be performed by only

certain organisms (eg. photosynthetic), nitrogen fcertain organisms (eg. photosynthetic), nitrogen fixation is performed only by a small number of baixation is performed only by a small number of bacterial species, including symbiotic bacteria (cterial species, including symbiotic bacteria (RhizRhizobiumobium) in the roots of leguminous plants.) in the roots of leguminous plants.

As you might predict, the reduction of NAs you might predict, the reduction of N22 to NH to NH33 i i

s a highly endergonic process (see Figure 13.1):s a highly endergonic process (see Figure 13.1):

Nitrogen fixation is catalyzed by a Nitrogen fixation is catalyzed by a nitrogenasenitrogenase complexcomplex

Electrons (& energy from reduction potential) aElectrons (& energy from reduction potential) are derived from 4 NADHre derived from 4 NADH

At least 16 ATP must be hydrolyzedAt least 16 ATP must be hydrolyzed The ammonia (NHThe ammonia (NH33) produced is either utilized ) produced is either utilized

by the nitrogen-fixing bacteria, or secreted into by the nitrogen-fixing bacteria, or secreted into the environmentthe environment

In the case of symbiotic nitrogen-fixing bacteriIn the case of symbiotic nitrogen-fixing bacteria, the NHa, the NH33 is transported into adjacent host cell is transported into adjacent host cells (where it is used in glutamine synthesis)s (where it is used in glutamine synthesis)

Note that a byproduct of nitrogen fixation is hyNote that a byproduct of nitrogen fixation is hydrogen gas (Hdrogen gas (H22))

Amino Acid Biosynthesis

Amino Acid Biosynthesis:Amino Acid Biosynthesis: Most prokaryotes, many simple eukaryotes, and Most prokaryotes, many simple eukaryotes, and

plants can synthesize all 20 amino acids used in plants can synthesize all 20 amino acids used in protein synthesis from simple organic precursors protein synthesis from simple organic precursors and metabolic intermediatesand metabolic intermediates

Mammals and other animals can only synthesize Mammals and other animals can only synthesize a subset of these amino acids; known as the 12 a subset of these amino acids; known as the 12 "nonessential" amino acids (see Table 14.1)"nonessential" amino acids (see Table 14.1) The remaining amino acids (8 "essential" The remaining amino acids (8 "essential"

amino acids) must be obtained from the dietamino acids) must be obtained from the diet this explains one of the primary reasons for this explains one of the primary reasons for

the requirement of protein in the dietthe requirement of protein in the diet

"Complete" proteins contain adequate amount"Complete" proteins contain adequate amounts of all the essential amino acidss of all the essential amino acids

generally derived from animals (meat, milk, generally derived from animals (meat, milk, eggs)eggs)

"Incomplete" proteins are deficient in one or "Incomplete" proteins are deficient in one or more of the essential amino acidsmore of the essential amino acids

generally derived from plantsgenerally derived from plants examples:   beans (low in methionine), cereexamples:   beans (low in methionine), cere

al grains (low in lysine), corn protein (low in al grains (low in lysine), corn protein (low in lysine & tryptophan), wheat protein (low in llysine & tryptophan), wheat protein (low in lysine)ysine)

Glutamate Family

GlutamateGlutamate (glutamic acid) is derived from (glutamic acid) is derived from -ketoglutarate-ketoglutarate , an inte , an intermediate in the Krebs Cycle, through direct incorporation of ammormediate in the Krebs Cycle, through direct incorporation of ammonium (NHnium (NH44

++):):

GlutamineGlutamine is derived from is derived from glutamateglutamate through direct incorporation through direct incorporation of ammonium (NHof ammonium (NH44

++):):

ProlineProline and and argininearginine are derived from are derived from glutamateglutamate through two very through two very different biosynthetic pathways.different biosynthetic pathways.

ProlineProline is synthesized through reduction of the carboxylic aci is synthesized through reduction of the carboxylic acid in the side chain of glutamated in the side chain of glutamate

Many amino acid biosynthetic pathways involve transamination reMany amino acid biosynthetic pathways involve transamination reactions:actions:

The The -amino group from one amino acid is transferred to an -amino group from one amino acid is transferred to an -keto acid to produce a new amino acid-keto acid to produce a new amino acid

Glutamate is a primary amino group donor in these reactions Glutamate is a primary amino group donor in these reactions (see serine biosynthesis below):(see serine biosynthesis below):

Serine Family

SerineSerine is derived from is derived from 3-phosphoglycerate3-phosphoglycerate (glycerate-3-phosphat (glycerate-3-phosphate), an intermediate in the energy-yielding phase of glycolysis, throe), an intermediate in the energy-yielding phase of glycolysis, through a series of reactions that include transamination (with glutamugh a series of reactions that include transamination (with glutamate as the amino group donor):ate as the amino group donor):

GlycineGlycine is derived from serine by removal of the hydroxymethyl g is derived from serine by removal of the hydroxymethyl group from the side chain:roup from the side chain:

AsparagineAsparagine is derived from is derived from glutamineglutamine through a transamination r through a transamination reaction (the amino group is derived from the glutamine side chain, eaction (the amino group is derived from the glutamine side chain, rather than the rather than the -amino group):-amino group):

Pyruvate Family

AlanineAlanine is derived from is derived from pyruvatepyruvate , the end product of glycolysis, t, the end product of glycolysis, through a transamination reaction (with glutamate as the amino grhrough a transamination reaction (with glutamate as the amino group donor):oup donor):

Histidine BiosynthesisHistidine Biosynthesis Histidine is synthesized through a complicated biosynthetic pathHistidine is synthesized through a complicated biosynthetic path

way that involves the production of phosphorylated nucleoside intway that involves the production of phosphorylated nucleoside intermediates ermediates

Alkaloids: Introduction

small organic molecules (secondary metabolites) of

plants which contain nitrogen (ussually in a ring) alkaloids, protoalkaloids, pseudoalkaloids structurally diverse: 12,000+ structures

20% of all plant species concentrated in specific plant taxa (families, genera,

species) biosynthetically diverse (families/types) strong biological effects (-> 3 ecological examples)

Historical and human importance:

pharmaceutically significant (often neurological) effect of N biological effects & uses: analgesic - pain killers (morphine)

paralysis, anesthesia (tubocurarine, coniine) stimulants (caffeine, nicotine) antitussive (codeine) emetic (emetine) anti-cancer drugs (taxol, vinblastine) toxins and antibiotics (quinine, sanguinarine)

Alkaloid Families and Biosynthesis

families classified by ring structure derived from amino acids [with a few exceptions]

Examples: tyrosine -> morphine (opium alkaloids) tryptophan -> quinine (quinoline) vinblastine (indole) glutamate (via ornithine) -> cocaine (tropane)

• - >nicotine (tobacco alk)• - > senecionine (pyrrollizidine)

aspartate -> nicotine xanthine -> caffeine, theobromine (purine)

General Features of Alkaloid Biosynthesis can have complex structures, many biosynthetic steps

& compartments (eg) vinblastine often found in mixtures of related compounds

pathway begins with decarboxylation (eg) tyr -> tyramine

may include other components - (eg) vinblastine, (dimeric indole terpenoid) solanidine (tripterpene alkaloids of potato)

organ specific synthesis and storage (bark, roots, flowers)

sequestered within cells and special structures (vacuole, latex vesicles, idioblasts, epidermis)

Biosynthesis

of Alkaloid

Steroid Alkaloid

the the Solanum Solanum typetype - one example is - one example is solanidinesolanidine. . This steroid alkThis steroid alkaloid is the nucleus (i.e. aglycone) for two important glycoalkaloialoid is the nucleus (i.e. aglycone) for two important glycoalkaloids, ds, solaninesolanine and and chaconine chaconine, found in potatoes. Other plants in t, found in potatoes. Other plants in the he Solanum Solanum family including various nightshades, Jerusalem chfamily including various nightshades, Jerusalem cherries, and tomatoes also contain solanum-type glycoalkaloids. erries, and tomatoes also contain solanum-type glycoalkaloids. Glycoalkaloids are glycosides of alkaloids. Glycoalkaloids are glycosides of alkaloids.

the the Veratrum Veratrum type.type. There are more than 50 There are more than 50 Veratrum Veratrum alkaloids alkaloids including including veratramineveratramine, , cyclopaminecyclopamine,, cycloposine cycloposine,, jervine jervine, and, and muldamine muldamine occurring in plants of the occurring in plants of the Veratrum Veratrum spp. The spp. The ZigadeZigadenus nus spp., death camas, also produces several veratrum-type of spp., death camas, also produces several veratrum-type of steroid alkaloids including steroid alkaloids including zygacinezygacine

Summery of Alkaloids

very toxic plant chemicals in common plant species toxic chemicals in food plants effective against generalist insects, but specialists have counter

adapted many alkaloids have documented multiple effects on different ta

rgets neurotransmitter receptors (nicotine, cocaine, morphine) neurotransmitter transport/degradation (cocaine) interfere with cytoskeleton (tubulin - taxol) ion channels (caffeine) enzyme inhibitors (caffeine, theobromine)