Question+5

=Question 5=

microscopic and macroscopic scale.
I cut it down to under two pages rather than 3 this time haha... added with scott's it will probably be over 3 so i'll look at it once more tomorrow to choose the most important info. Question 5B What are the microscopic and macroscopic interactions of Nicotine with the body from ingestion to excretion? The most common source of nicotine is through tobacco smoke, where it is the primary alkaloid and ‘active ingredient’, 95% of the alkaloids in tobacco are nicotine. (Hukkanen et al. 2005) Because nicotine is most commonly ingested this way and is the primary alkaloid in tobacco smoke we will analyze this case. Because nicotine is an alkaloid, it can be found in two forms depending on pH. In a more acidic environment it will be protonated and may accept an oxygen ion (figure Nicotine-N-Oxide) causing it to be polar and thus unable to pass through cell membranes effectively, or in a more basic environment it will form normal nicotine (figure Nicotine) which less polar and can pass through cell membranes more easily. (Hukkanen et al, 2005) while being inhaled and absorbed, the pH of cigarette smoke can range from 5.6-6.3 (Brunnemann, K.D., Hoffmann, D, 1974) this means that the nicotine is protonated and cannot enter cells until it is dissolved into more basic substances like bodily fluids. Once the nicotine reaches the alveoli it is allowed to dissolve into the blood, which is very slightly basic (pH of 7.4). This increase in pH shifts the equilibrium of protonated and non-protonated nicotine such that 31% of the nicotine can become non-protonated and pass through cell membranes. (Hukkanen et al, 2005) Nicotine is mainly distributed to the liver, kidney, spleen and the brain, however ionized nicotine sometimes accumulates in the acidic areas of the body like the stomach (gastric fluid) and the mouth (saliva). (Hukkanen et al. 2005) Nicotine In the brain will bind to acetylcholine receptor sites, (Barrows et al 1986) this causes the desired effect for the addict. Wh en it reaches the liver, the nicotine is metabolized mainly into cotinine (75-80%) which is broken down further, but there many other metabolites like Nicotine N oxide and more illustrated in figs. (pathways charts) one more notable metabolite is 4-(methylamino)-1-(3-pyridyl)-1-butanone. This metabolite is thought to be converted into NNK which is a known carcinogen, however this has not been detected. (Hukkanen et al, 2005) Cotinine itself is metabolised further into many different compounds, in fact the most commonly detected metabolite found in urine is a metabolite of Cotinine, 3-hydroxycotinine, which accounts for about 40% of excreted nicotine metabolites. (Hukkanen et al, 2005) 90% of a nicotine dose can be identified in the urine of the smoker, it is 40% 3-hydroxycotinine, 15% cotinine glucuronide, 10% cotinine, 8% 3-hydroxycotinine glucuronide, 6% nicotine N-oxide, 5% nicotine glucuronide, and some others in trace amounts. This illustrates that nicotine is not completely broken up like starches or fats, and most of its structure remains as it travels through the human body.

(my diagrams are embedded in the doc and are not separate files so they could not go on the wiki, sorry!)