BOT 380: Purinergic Stimulants

What is the most commonly used stimulant worldwide

Methylxanthines — stimulates CNS at all levels but is milfer than other stimulants

When was caffeine discovered and how

1821 — when searching for quinine alternatives

What are the most commonly used stimulant methylated xanthine compounds

Caffeine, theophylline, theobromine

What is the function of compounds that have purinergic activity

Modulate (activate/inhibit) purine NT action (endogenous NT = adenosine)

What are the CNS physiological effects of caffeine

Increase alertness, induces insomnia, improves energy and mood

What are the physiological effects of caffeine on the periphery

Stimulates skeletal muscles (endurance), improve psychomotor performance, simulate bronchial tubes and coronary arteries, increase HR and BP, increase metabolism, diuretic

What is the mechanism of adenosine

Endogenous inhibitory NT — causes behavioural sedation by inhibiting most NT from entering the synapse

What is the cellular mechanism of caffeine

Binds to adenosine receptors to compete with adenosine — antagonizes normal function

Potency of Methylxanthines as CNS and skeletal muscle stimulators (most to least potent)

Caffeine >> theophylline >> theobromine

Potency of Methylxanthines as cardiovascular stimulates (most to least potent)

Theophylline >> theobromine >> caffeine

Which plant does coffee come from

Coffee arabica

Which plant does tea come from

Camellia sinensis

Which plant does the cocoa tree come from

Theobromine cacao and cola acuminata

Which plant does mate come from

Ilex paraguariensis

Which plant does guarana come from

Paulina cupana

What is the historical use for methlxanthines

Cure for measles

What is the the modern use for Methylxanthines

Part of non-prescription pain remedies

Used to treat asthma — dilate bronchioles

Which Methylxanthine compound is the most used for CNS stimulant effects

Caffeine — effects heightened by carbonation

How did they discover caffeine in Ethiopia (850 AD)

Goat herder noticed lively goat behaviour and correlated it to feeding on kaffa plants

How did they discover caffeine in Yemen

Saw similar effects on goats (thought it was brought by Ethiopians)

Began to drink k'hawah — tasted crushed berries with water or mix coffee beans with fat as a food source

Describe the coffee beans

2 seeds found within the fruit (berry/drupe)

Describe the evolution of the coffee drink

Originally the whole berry was steeped in hot water

13th century Yemen: roasted seeds

1500s: cultivated coffee tree — spread through Arabian world

Describe the evolution of coffee production

Arabia had monopoly on coffee at 1st

Dutch then set up their coffee plantations in their colonies (Ceylon/Sri Lanka, Java) — ended Arabian monopoly

Grew beans in Caribbean and South America

Who are the current leading producers of coffee

Colombia and Brazil

Describe coffee spp in Africa

C.liberica and C.canephora

Coffee canephora

Used to make instant and decaffeinated coffee

Resistant to fungal pathogens that causes coffee rust and kills C. Arabica

Describe coffee fruit development after fertilization

Seeds are surrounded by fleshy tissue during development — begin caffeine synthesis

When has the fruit of coffee spp. reached its max caffeine concentration

When berry is red colour (2% of dry weight)

What happens to caffeine concentration if berries are left on the tree for a longer period of time

Undergoes maturation and desiccation: seeds and fruit lose water (30% to 6%)

Desiccated seeds can germinate and produce seedling

Describe the caffeine content in a matured berry

Caffeine concentration falls from 2% to 0.03% of dry weight

Why do plants produce caffeine

Fruit = vulnerable to insects

Caffeine (2%) in fruit: lethal dose for tobacco hornworm/causes sterility in some beetles; acts as a deterrent

Caffeine (4%) in shoots/young leaves

Genus cola

Found in rain forests of tropical west Africa

Seeds form in fruit pods and contain 4-15 reddish brown seeds = cola nuts

Cola nuts

High caffeine content

Used to depress appetite

Used in religious rites and were though tot have aphrodisiac properties

What are 2 commercially important cola spp. grown in West Indies, Brazil, and Sudan

Cola nitride and cola acuminata

Theobromine cacao

Used to make chocolate by the aztecs

Pod shaped fruits have large seeds — roasted to make chocolate liquor and cocoa butter

Have high levels of theobromine > caffeine

Describe the synthesis of caffeine

1. Xanthosine > 7-methylxanthosine by XMT enzyme

2. 7-methylxanthosine > theobromine by MXMT and CS/TS enzymes

3. Theobromine > caffeine by DXMT and CS enzymes

Describe the protein sequence of Nmethyltransferases from the caffeine biosynthetic pathway

Have high protein sequence homology (<80%) — but they exhibit substrate selectivity

Describe why genetic engineering may be done during the production of caffeine

Increase caffeine levels in coffee

make plants that normally don't produce caffeine to start

Reduce levels of caffeine (decaffinate) by knocking out key enzymatic steps

What are the effects of caffeine on leaf borer

Transgenic (tr-1 and tr-2) caffeine-producing tobacco plants repel tobacco cutworm compared to WT

How does caffeine help pollinators

It can enhance their memory of reward

Describe how genetic engineering is done to alter purine alkaloid metabolism

Can decaffeinate coffee plants — target MXMT gene

Can build caffeine metabolism into new plant spp. — express CaMXTM/DXMT genes