![]() ![]() These receptors are expressed in the brain, immune system, and cardiovascular system. The four types, A1, A2B, A3 and A2A are all members of the G protein coupled receptor, which is a membrane spanning protein. There are four different types of adenosine receptors that bind and activate adenosine, the ligand for that receptor. A2A receptor is one of many adenosine G protein-coupled receptors (Huang et al 2014). ![]() As adenosine receptors bind G-protein, neural activity begins to decrease and the person feels fatigued and sleepy. Adenosine binds intracellularly to G-protein and induces multiple effects. Within the brain, concentration of this neuromodulator increases every hour. Adenosine is a polar molecule and is water soluble. It has two components an adenine nucleotide and a ribose sugar (Figure 1). The synthesis of Caffeine from Xanthosine.Īdenosine is an inhibitory neurotransmitter, which promotes sleep and inhibits arousal. DXMT converts a third SAM to SAH, adding a methyl group to the 1’-Nitrogen, yielding a caffeine molecule (Denoeud et al 2014).įigure 2. This produces theobromine which undergoes another methylation step with the help of the enzyme DXMT. The second enzyme, MXMT, converts another SAM to SAH, subsequently adding a methyl group to the 3’- Nitrogen on 7-methyl-xanthine. This produces the intermediate 7-methyl-xanthosine to become 7-methyl-xanthine (Denoeud et al 2014). The first step of caffeine biosynthesis involves XMT converting S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) which removes a methyl group and adds it to the 7’-Nitrogen. In order to synthesize caffeine, xanthosine must undergo 3 methylation steps with the help of three NMT enzymes (Figure 2) xanthosine methyltransferase (XMT), theobromine synthase (MXMT), and caffeine synthase (DXMT) (Denoeud et. Mechanism of Caffeine (Trimethylxanthine) SynthesisĬaffeine is a naturally occurring methylxanthine, purine alkaloid, synthesized by eudicot plants such as coffee, cacao, and tea (Denoeud et. Caffeine affects neurons and glial cells in the brain by binding to the same location that adenosine would bind and induce a cascade of enzymatic downstream effects (Denoeud et al 2014).įigure 1: The molecular structure of Caffeine and Adenosine. They antagonize or inhibit many of the adenosine receptors, like the A2A receptor. It is composed of purines structurally it is polar, and water soluble (Figure 1). 6 How Caffeine (Trimethylxanthine) BindsĬaffeine, systematic name is 1,3,7-trimethylxanthine, is a xanthine derivative.5 Structure of Adenosine (A2A) Receptor.2 Mechanism of Caffeine (Trimethylxanthine) Synthesis.Based on available evidence, it is suggested that reproductive-aged women should consume </=300 mg caffeine per day (equivalent to 4.6 mg kg(-1) bw day(-1) for a 65-kg person) while children should consume </=2.5 mg kg(-1) bw day(-1). The data also show that reproductive-aged women and children are 'at risk' subgroups who may require specific advice on moderating their caffeine intake. Based on the data reviewed, it is concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg day(-1) (equivalent to 6 mg kg(-1) body weight day(-1) in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behaviour, increased incidence of cancer and effects on male fertility. The possibility that caffeine ingestion adversely affects human health was investigated based on reviews of (primarily) published human studies obtained through a comprehensive literature search. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Caffeine is probably the most frequently ingested pharmacologically active substance in the world. ![]()
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