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Gut Bacteria For IBS – What Can They Do For You?

It is a well known fact that the gut has a major role to play in the well being and health of an individual. As part of the digestive system, it is one of the most important parts of the human body, as it helps to break down the foods that we eat. The bacteria that naturally live in our stomachs also help to digest the food we eat. This is why having healthy bacteria in the stomach is so important. However, if this bacteria is not well maintained, then it can cause serious health problems.

A balanced diet and proper daily exercise are both essential if you are going to get your body back into shape. However, there are certain bacteria that may be present in the body but are not beneficial. This can lead to an imbalance with the good and bad bacteria and can result in health issues. This is where probiotics come in.

gut bacteria enhances well being

Probiotics are living organisms that are present in the gastrointestinal tract. They are known to have a role in maintaining the balance of microorganisms in the digestive tract. The bacteria will help to kill harmful bacteria in the digestive tract, which in turn helps to maintain the natural balance of the population. The imbalance can be caused by the use of antibiotics and other prescription medications that are taken by individuals. These drugs wipe out the bacteria in the GI tract along with other helpful bacteria. There is a severe reduction in the normal flora of the gut.

Bacteria in supplements form a major part of a healthy lifestyle.

It is important for individuals to realize that it is possible to get these bacteria from supplements rather than through diet. In addition, some foods are also well known sources of these good bacteria but may not be available to many due to geographical limitations. This is where supplements can be useful. You will need to find out from your physician if there are any foods that you need to avoid as they can be high in bacteria and it can enhance your health in ways you never thought possible.

Probiotics: What is it, Benefits, Side Effects, Food & Types

Your health will improve by having bacteria in your body. There are a number of different species of bacteria which are good for your health. They prevent many conditions such as XNXX IBS, colitis, diabetes and obesity. This means that they help to increase your health and well being. The main source of these bacteria is yogurt which is eaten daily and is considered to be one of the best food sources of probiotics.

There are a number of different supplements that are available. The way you take them is up to you. These supplements help to restore the normal flora in the gut, which can be lost as a result of stress, poor diet, or antibiotics. You will need to take these supplements regularly if you wish to retain your health and well being.

Some people feel that taking these supplements on their own is sufficient.

However, research has shown that if you are suffering from any health condition including IBS, this can make your condition worse as your body will not have the ‘good’ bacteria to help keep it under control. For this reason, it is essential to take them alongside a healthy diet, lots of water and a good dose of tukif videos.

The good news is that there is no evidence that introducing gut bacteria into the body will cause any harm. In fact, studies have shown that they can have a positive effect. By restoring the ‘friendly’ bacteria in your gut, you can help to improve your digestive system and your overall health. This is why the use of probiotics for treating IBS is growing in popularity.

The human body possesses a food channel nine meters long, open on the environment at both ends. It’s population of millions of microbes: fungi, bacteria, and viruses. Additionally, there are harmful intestinal parasites (worms, amoebae, giardia) that may also be present. Our food channel fills with intestinal bodies shortly after birth, during normal vaginal childbirth. This does not occur during a Caesarian delivery.

These are the bodies that help newborns digest milk. If a cesarean section is followed by limited breastfeeding, filling the gut with good germs is delayed and different. Some researchers think this difference is the cause of increased asthma, allergies and obesity in children. It can even contribute to their thirst for fast food and supercharging due to the lack of feeling of satiety.

A powerful force

Microbes are usually symbiotic and are fed by the food we eat. Throughout their lives, they secrete chemicals whose important task is to trigger processes such as digestion and immunity. Their importance is not only that, these bacteria also produce vitamins such as K and B12. The other chemicals they secrete have different impacts on the body’s various systems. It has been observed that people with neurological diseases such as autism, Parkinson’s, depression, Alzheimer’s, schizophrenia have other gut microbes.

The specific balance of flora is also linked to obesity. It has been found that people who “put on weight easily” and find it impossible to “get rid of” have particular types of intestinal flora.

Medications Vitamins Antibiotics - Free photo on Pixabay

Antibiotics act like some kind of blind army. They can’t just target the germs that cause the disease and kill many good organisms. For this reason, very often, people develop diarrhea after antibiotic treatment. Vitamin production in the intestine is also reduced, leading to a lack of vitamins and causing cracks in the angle of the mouth or tongue’s angle.

To prevent these side effects probiotics may be given at the same time as or after antibiotic treatment. Supplements are generally in the form of capsules which contain cultures of lactobacillus, porno bifidobacterium and Saccharomyces boulardii yeast.

Sometimes probiotic compounds are combined with prebiotics. This is referred to as synbiotic. Serving as food for probiotic organisms: prebiotics are compounds such as pectin.

Not only probiotics are live organisms, but they usually need to be keep within the fridge, kept as instructions demand and ingested before the expiration day. These supplements (but not natural kinds of probiotics) should not be administered to critically unwell people, people who have recently undergone surgery or those battling against cancer. Even with children, they should be administered with careful detail.

Self-improvements for a better gut bacteria

And do not be fooled for most charlatans claim enhancing gut flora is expensive. There are great supplements available online. It is only a choice of habit.

Going without food, but not water, for 24 hours helps to develop a healthy gut biome.

Regular exercise changes the gut flora such that immunity improves and inflammation becomes less. This is seen particularly in endurance athletes. But the effect wears off if a practice is discontinued.

Avoid highly processed foods with trans fats, preservatives and coloring, especially high-calorie snacks of no nutritional value.

It is advised against to replace sugar with artificial sweeteners this is mainly done by diabetic people or those who want to lose weight; they don’t know they are disrupting the microbes’ metabolism.

Eat at least four helpings of different-coloured fruits and vegetables throughout the day.

Drink the required water for the day, that is 2.5 to 3 litres of water a day.

Coffee and tea, mainly green tea as well as nuts, contain antioxidants called polyphenols. Good microbes thrive in their presence.

Add fermented food to your diet. Taking 30ml of homemade curd first thing in the morning will help repopulate the gut.

Oils, Fats & Waxes

oils-fats-waxesOils, fats and waxes are mixtures of glyceryl esters of carboxylic acids, compounds consisting of an aliphatic chain and a -COOH end. Some of the acids, shown below, exist in the free state. When double bonds exist in the alkyl chain, the compounds are said to be unsaturated. Polyunsaturated compounds have two or more double bonds. These double bonds are areas of high electron density which make for high reactivity. Electrophilic addition at double bonds is one of the main methodologies of organic synthesis.
saturated carboxylic acids

The saturated fatty acids include many well-known compounds. Formic acid is preset in bee stings. Acetic acid gives vinegar its sour taste. Propanoic acid, and to a greater extent butyric acid, are present in dairy products, from decomposition of esters. Hexanoic and dodecanoic acids can be isolated from coconut oil, though they are not the main constituents. Capra is Greek for goat: capric, caproic and caprylic acids occur in goat cheeses.
Hexadecanoic acid is known as palmitic acid because it is the major constituent in palm kernel oil. Octadecanoic acid, the main component of beef fat, is known as stearic acid. Arachidic acid is present in large quantities in peanut and some fish oils. Docosanoic acid is present in most seed fats, such as mustard seed oil and rape seed oil.
The length of the carbon chain on a given acid determines the volatility of the pure substance. Higher molecular weight acids have lower vapor pressure and a higher tendency to condense into a liquid or solid. Thus, acetic and formic acids are volatile liquids; vinegar will lose its acrid flavor if left uncovered as the acetic acid evaporates. But, a compound like palmitic acid is a solid, and will evaporate very slowly. Double bonds in the chain (see below) complicate the process of coordination during solidification, compared to compounds of the same molecular weight with no double bonds. Thus olive oil is a liquid while butter is a soft solid at room temperature. This trend is seen in bulk products like animal fats, composed of triglycerides (below), which are esters of fatty acids. The fat from hogs which are fed soybeans has a higher proportion of unsaturated fats and melts lower than the fat from hogs with limited soy intake.
unsaturated acids

Sorbic acid (2,4-hexadienoic acid) is used in various forms as a preservative; it probably works by inhibiting active sites on bacterial enzymes. Vaccenic and petroselinic acids are less well known 18-carbon (octadecaenoic) acids. Oleic acid is the main constituent of olive oil.
Linoleic, linolenic, and arachidonic acids are termed essential fatty acids because the body cannot synthesize them from other acids. They can be found in various vegetable oils such as peanut, sunflower and soybean, and are used to synthesize the prostaglandin, leukotriene and thromboxane families of endogenes. Gamma-linolenic acid is an intermediate in this process. Variants like EPA (an eicosapentaenoic acid), known as omega-3 oils, commonly found in fishes, can be used as antihyperlipidemics, compounds which reduce the level of low-density lipoproteins (LDLs) in blood.
Tung oil, a drying oil, contains mainly eleosteric acid, cis-trans-trans-9,11,13- octadecatrienoic acid). The unsaturated bonds in drying oils help paint polymerize into a solid matrix.
toxic oils

Tuberculostearic acid and TMTA are secreted by tuberculosis cells; the latter compound is the primary toxin. Ricinoleic acid is a substituted oleic acid derivative implicated in demyelinization of nerve fibers. Crynonycolenic acid is derived from the diptheria bacillus.
The urushiols are a family of oily allergens secreted by poison ivy, oak and sumac. Oils like these – consisting of an aromatic ring and a long aliphatic chain – may persist for years, but may still be easily removed by detergents. The anacardic acids are related compounds. Embelin is another naturally-occurring irritant oil.
esters & waxes

Esters are organic compounds arising from a combination of a carboxylic acid and an alcohol, giving the R-CO-O-R linkage shown. Low-molecular weight esters give fruits their characteristic odors and flavors. It is interesting that almost all the low-weight esters smell pleasant, while their acid counterparts are unpleasant to the human sense of smell. This is simply an artifact of our evolution; not surprisingly, a selective advantage was gained by organisms which turned up their noses at rotting foods but ate fresh ones! The coevolution of flowering plants (angiosperms) and humans is an interesting story in its own right.
The higher molecular weight esters are solid waxes. The hardness of the wax depends directly on its composition of various esters. Carnauba wax is high in ceryl cerotate, which has two chains of equal and substantial length, which impart hardness. Beeswax is high in an ester with one very long chain and one shorter chain, giving it a somewhat softer property. Spermaceti, from the cranial fluid of sperm whales, is rich in hexadecyl palmitate (16 carbons to either side). This oil burns well in a lamp, and was used extensively historically.

All the natural animal and vegetable fats and oils are composed of esters of glycerol, a tri-alcohol or triol, and various fatty acids. These glyceryl esters are known as triglycerides. The physical properties like melting point again depend on the various chain lengths involved, with longer chains giving lower melting points and double bonds/unsaturation raising the melting point.
In the blood, triglycerides are further packaged into pockets of fat and protein called lipoproteins. The lipoproteins are of various sorts, primarily what are called high and low density lipoproteins (HDLs and LDLs).
In addition to providing energy through lipolysis (fat burning), triglycerides contribute to the structure of cell walls, which are fatty acid (phospholipid) bilayers. Nerve cells also rely heavily on the properties of phospholipid membranes. Sequestration of water environments inside lipid bilayers probably played an important role in the origination of life, since copy errors are less punitive in a protected environment.
olestra (Olean) & Xenical

Olestra is a non-absorbable cooking oil which is made by combining vegetable oil and sucrose in a molecule with physical characteristics similar to fat/triglyceride. While triglycerides consist of a glycerol core with three fatty acids attached, olestra is composed of a sucrose core with six to eight fatty acid chains attached. This structural configuration prevents olestra from being metabolized by digestive enzymes or colonic microflora. Therefore, olestra is not broken down or absorbed from the gastrointestinal (GI) tract, and no calories are released. Studies show this compound is non-toxic, imparting the taste sensation of fat without the calories, but the fact that it is not absorbed causes some unpleasant side-effects such as fatty stools. As with many recent chemical novelties, the long-term effects are uncertain.
Xenical is a recent weight-loss drug that works by binding to lipolytic enzymes and inhibiting fat absorption. This mechanism is in stark contrast to the stimulant approach to combating obesity.
composition of common fats and oils

Because they are mixtures of glyceryl esters of various carboxylic acids, it is impossible to show a chemical structure for a “butter molecule” or an “olive oil molecule.” Mixtures cannot be broken down into a single entity which when isolated retains the properties of the whole. One can however resolve the mixture into its component compounds, which for natural fats and oils are esters of carboxylic acids. The results for some common oils and fats are shown here schematically in bar plots. To the left of the vertical axis are plotted the saturated components of various chain lengths. To the right are the unsaturated components.
Recent studies suggest that a diet rich in animal fats may increase the risk of fat-related morbidities as one ages, incuding colorectal cancer, heart disease and arteriosclerosis. These effects probably arise from several compounds, i.e. cholesterol, as well as saturated fats, and are probably exacerbated by synergism with toxins such as nicotine (i.e. nicotine may irritate the lining of blood vessels and promote plaque binding).
Beef and palm oils are high in unsaturated components (stearic and palmitic), but still have appreciable monounsaturates. Coconut is the really “evil” oil, high in low-molecular weight saturated fats.
Vegetable oils have lower cholesterol content and are considered healthier as a group. Hydrogenation renders them harder (more solid) and imparts a more fat-like texture, but probably negates this health benefit despite retarding further oxygenation.
Olive and peanut are high in monounsaturates. A diet high in olive oil may contribute the suppleness of skin endemic to the Mediterranean peoples.
According the current literature, the “healthier” oils contain high concentrations of unsaturated oils, particularly polyunsaturates. Soybean, canola (rape seed), sunflower and corn oils are high in polyunsaturates. There is some evidence, though, that excessive polyunsaturates impart their own health detriments. Polyunsaturated oils such as rape seed have been used to aid the polymerization process in paints and lacquers: the double bonds link other structures together by donating bonds. Even linoleic acid is a semi-drying oil. Furthermore, the all-cis forms of these polyunsaturates are energetically unstable and trans forms, known to be unhealthy, are thus more likely to occur.
ketone bodies and ketogenic diets
A diet rich in fats and oils but poor in carbohydrates and proteins is termed ketogenic because it promotes the formation of ketone bodies. These are small acids and ketones which shift the pH of blood away from the physiologic norm around 7.0 (acid neutral). Such compounds arise in the blood as a result of alcoholism and diabetes; the syndrome, whatever its etiology, is termed ketosis.
High-protein diets such as the popular Atkins diet work by starving the body of carbohydrate (sugar-based) nutrition. This induces the other main mechanism of oxidative organisms, beta-oxidation of fatty acids. Presumably, enzymes responsible for the latter mechanism are induced, leading to fat loss and thus weight loss. Pursued within reason, such an approach is not unhealthy, though in extremes it can of course be dangerous.

Flavors & Fragrances

Flavors & Fragrances
Flavors & Fragrances

Here is a collection of compounds with noticeable flavors or aromas. In addition to sweeteners like aspartame and sodium cyclamate are fragrant compounds like menthol and camphor. Many of these are terpenes, a class of volatile alkene compounds consisting of rearranged multiples of the isoprene unit, the monomer of natural rubber. There are some musk compounds used in perfumery, and the spicy compounds in peppers and mustard. Finally there are some rather unpleasant-smelling chemicals like putrescine and cadaverine, which arise in rotting meat. Formal sugars can be found on the sugars page.
Most of these chemicals are generated by plants. In some cases there is an evolutionary reason for this, either to attract animals or insects by an attractive scent or to deter them with an unpleasant one. Other compounds may serve antibiotic or antifungal ends in the vegetable host. In other cases they may prevent dehydration or provide a pigment to encourage pollination. Still others may be artifacts of some other chemical process.
fruit esters

Esters are organic compounds arising from a combination of a carboxylic acid and an alcohol, giving the R-CO-O-R linkage shown. Low-molecular weight esters give fruits their characteristic odors and flavors. It is interesting that almost all the low-weight esters smell pleasant, while their acid counterparts are acrid and repellent. This is simply an artifact of our evolution; not surprisingly, a selective advantage was gained by organisms which turned up their noses at rotting foods but ate fresh ones. The coevolution of flowering plants (angiosperms) and humans is an interesting story in its own right.
The relation of the smell brain (rhinencephalon) to intelligence is an old story. It is argued that one reason for mammals developing their reasoning powers was that our verminous ancestors, small rats rummaging around for dinosaur eggs, were primarily nocturnal. Along with the development of sensitive olfactory organs – tiny molecular analyzers – they had to interpret the smells. This is a lot harder on a neurological level than the task the brains of the dinosaurs were charged with, which amounted to “chase and eat.” The development of the cerebrum directly parallels that of the smell brain. To this day, smells remain extremely strong triggers of emotions, more so than sights or sounds.
aromatic compounds

Aromatic compounds (arenes) contain a benzene or benzene-like ring structure. The delocalized pi bonding in this uniquely stable structure accounts for the chemical and physical properties of the liquid: most arenes are volatile liquids at room temperature. This pi-electron cloud also contributes to the olfactory response. Often this is perceived as a cloying sweetness, redolent of ketones, which also contain delocalized double bonds. The nose is a remarkable chemical analyzer whose detailed workings, like those of the other senses, are incompletely understood.
The other major division of organic hydrocarbons is aliphatic. Aliphatic compounds may contain rings, but not resonance-stabilized pi bonds.

Terpenes are volatile plant compounds with distinctive scents. Breaking a twig or crushing a leaf releases these compounds; depletion results in a stale taste. Fenchone, camphor and menthol are counterirritants; adding menthol to tobacco reduces throat irritation.
Essential oils are extractions (solutions) of plant materials, often rich in terpenes. Many of the terpenes impart CNS depressant effects (as do other organic solvents); they interact with neuronal phospholipid membranes and alter the function of ion gates and receptors. Absinthe, a distillate from wormwood, at one time contained thujone, and was a favorite drink of van Gogh’s (see the sedatives page).
Many of these compounds are also antiseptic; Listerine, as it is presently constituted, contains thymol, eucalyptol and menthol in addition to alcohol.
non-nutritive sweeteners & flavor enhancers

Saccharin is the only truly non-calorific sweetener in common use. First isolated from coal tar, it is a proven carcinogen, though in doses many times what one would get from food. Aspartame, a variation on phenylalanine, has about the same number of calories per gram as sugar (4 per gram) but is 180 times as sweet. It has less of the bitter aftertaste of saccharin. The cyclamates were removed from the US market over 20 years ago as suspected carcinogens; their taste was reputedly much closer to that of sugar than saccharin or aspartame.
Sucralose is a halogenated form of sucrose; appending chlorine groups where hydroxy (-OH) groups occur, in three positions, results in a molecule that the body’s enzymes cannot metabolize. [Compare to olestra, an altered form of fat.] Sunett (acesulfame potassium) is a saccharin-like compound with similar taste. Newer philosophies of application often involve mixtures of artificial sweetener and sugars. Equal, which contains dextrose and maltodextrose as well as NutraSweet, is one example.
Monellin is a polypeptide about 3,000 times as sweet as sucrose, from the serendipity berry. Thaumatin is another polypeptide, about 100,000 times sweeter than sucrose.
hot spices

The red pepper principle capsaicin initially causes intense irritation followed by desensitization to pain. The mechanism for this is probably through substance P or endorphin release. These compounds modulate pain impulses both in the CNS and peripherally. Capsaicin has found recent application in topical preparations and has been said to elevate mood. Receptors in the digestive tract respond to capsaicin by releasing cytoprotective substances such as prostaglandins and mucus. Capsaicin also works as a natural decongestant. In addition to cayenne, all hot peppers contain capsaicin, as does the spice paprika. Capsaicin is also used as natural insecticide/pest deterrent.
Whole peppers and their extracts contain many other chemicals besides capsaicin, of course, abundant carotenoids (vitamins A), thiamine, vitamin C, gingerol, and assorted other organic alcohols/terpenes.
Other hot spices have their own irritant chemistries. The black pepper principles are chavicine (cis form) and piperine (all trans form). In any peppercorn there is a mixture of these two forms, with chavicine being a little sharper to the tongue. When pepper goes stale, the percentage of chavicine decreases, which the tongue perceives as staleness. Grinding the pepper facilitates the isomerization process by reliving local steric constraints that maintain the higher-energy cis forms in the peppercorn. Methysticin is another pepper compound which resembles kavain, the active ingredient of kava. Cubebine, from Java pepper, resembles the black pepper constituents.
Black mustard contains sinapine, also present as a fragment of a larger chemical (sinalbin) in yellow mustard. Sinigrin is present in horseradish as well as black mustard.
Garlic contains several sulfurous compounds with antibacterial properties including allin and allicine. Ajoene is also an antithrombitic (blood thinning agent).
1-methylpropyl-1-propenyl-disulfide is one of several organosulfur compounds from asafetida (“devil’s dung”), a rare spice. Butyl mercaptan and dicrotyl sulfide are the major odiferous principles in skunk spray.
Finally, several isothiocyanates and indoles (mustard oils; not shown) in cauliflower are responsible for the burning sensation at the core of that vegetable and several related cruciferous vegetables including broccoli; these principles may convert estrogenic steroids to more benign forms (cancer-preventative).
musk chemicals

Musks are exocrine compounds of mammals, used to mark territory or as pheromones. These include muscone and exaltolide. Synthetic chemicals such as musk baur, which stimulate the olfactory receptors in similar ways, have been created for the perfume industry. These are typically easier to synthesize than the genuine compounds, which contain large rings (macrolides). Needless to say, there is a whole industry behind odor molecules which is byond the current scope 🙂
putrefaction products

Decomposition of proteins leads to many malodorous organic amides including putrescine and cadaverine. Spermidine and spermine are polyamines formed from putrescine; these compounds were first detected in semen but occur widely. They are used in biochemical research: they interact with DNA. Neurine, a choline putrefaction product, has a fishy odor, and is present in fish. Pellitorine is a plant insecticide.
Oxidized fats, prevalent in fried foods, pose a health risk over the long term. 3-(1,3,5,7,9-dodecapentanyloxy)-1,2-propanediol, a potent mutagen present in human feces, has been implicated in colon cancer.

Amino Acids

Amino Acids
Amino Acids

Amino acids are small organic acids containing an amine (-NH2) group and a carboxylic acid group (-COOH). In solution these two terminal groups ionize to form a doubly-ionized, though overall neutral entity called a zwitterion. The amine donates an electron to the carboxy group and the ionic ends are stabilized in aqueous solution by polar water molecules.
Amino acids are the basic building blocks of proteins, which are long chains or polymers of amino acids. In living systems, the instructions which code for the cellular synthesis of a specific protein are contained in nucleic acids (DNA); the process of protein synthesis from the genetic information is termed expression.
Twenty or so amino acids are termed essential because the body cannot synthesize them from other amino acids. Bulk proteins, as in animal muscle tissue (meat), contain an abundance of all varieties of amino acids, which are liberated in the stomach by cleavage by proteolytic enzyme. Some amino acid oligomers pass the lacteal boundary and enter the bloodstream, where they constitute a toxic threat as proteins not endemic to the organism.

Phenylalanine and tyrosine are the two major precursors to dopamine, epinephrine (adrenaline) and norepinephrine, the body’s three “fight or flight” hormones. Tryptophan is the main precursor to serotonin, an important inhibitory neurotransmitter controlling the stimulative adrenalin group compounds. Tryptophan is also used by the body to synthesize vitamin B3 when insufficient B3 is derived from diet (or from the symbiotic flora present in the GI tract). Glutamine is precursor to glutamate and GABA, two central neurotransmitters. Glutamate and aspartate also function as neurotransmitters in the brain. In addition, glutamate combines with cysteine and glycine ans the mineral selenium to form a tripeptide free-radical chelating agent called glutathione. Glutamine is also burned by the brain as a fuel, and basically imparts a feeling of energy. GABA is an ubiquitous inhibitory amino acid, both centrally and peripherally.
Leucine is used by the body to regulate blood sugar levels; one can increase one’s blood sugar by consuming isoleucine, which competes for absorption with leucine, reducing blood leucine levels. (All but the simplest molecules compete for absorption across the lacteals in the intestine.) Leucine, isoleucine and valine are called branched-chain amino acids; they are metabolized in muscle tissue and are important for muscle synthesis. Proline, a non-essential amino acid, is a major constituent of collagen.
Serine and threonine contain alcohol (-OH) groups, which can be used as active groups in enzymes, as can sulfhydryl (-SH) containing aminos. Methionine and cysteine constitute the major sulfur-containing amino acids; they are important in maintaining elasticity in peptide macromolecules like hair, skin, and fingernails, since bonds between protein strands are typically disulfide bonds. Methionine is a rich constituent of meats, but is lacking in most vegetables. Lysine is another amino acid important to collagen formation, bone growth, etc., which can be lacking in vegetarian diets. Methionine is also important for metabolizing toxins like alcohol and acetaminophen, for example. Along with cysteine, it has the ability to chelate heavy metals.
Histidine is the precursor of histamine, which is the body’s messenger of allergic response. Consuming more histidine, rather than making one more susceptible to allergic reaction, may help decrease the number of helper cells, reducing allergy symptoms. Arginine is important in immune function, sperm production, and wound healing, and may reduce blood cholesterol levels.
Carnitine is one of the so-called catabolic amino acids; it aids in transporting fat for oxidation (lipolysis). Taurine is another catabolic amino acid which probably performs inhibitory functions in the CNS. It is “conditionally essential,” important mainly during development. Taurine levels are characteristically low in brain tissues following epileptic seizures. Aspartate and methionine also perform catabolic functions. These are important when losing weight, or when changing health-related habits such as smoking or alcohol consumption, since the body must tear down or reconstitute old structures as well as building new ones (anabolics). Carnosine is a dipeptide constituent of muscle tissue, as its name implies. Calanine is a putative anticancer agent from legumes which forms covalent oximes with vitamin B6-cotaining enzymes. Canavanine is a similar aminooxy compound with enzyme-inhibiting properties, foundin legumes and alfalfa.
Cysteamine is a sulfhydryl compound used as an antidote to acetaminophen poisoning. Kyurenine and kyureninic acid are produced in body from tryptophan; this production is stepped up in B-vitamin avitaminoses. Djenkolic acid occurs in the djenkol bean; it is structurally similar to cystine, the dimeric form of cysteine. Hypaphorine is a convulsive poison similar to tryptophan.
proteins & chemical evolution
Proteins are one of the main products of DNA. Genetic codes in chromosomes allow cells to generate or express specific proteins using amino acids as building blocks. Through this means, DNA builds cellular machinery and controls its environment. The famous Miller experiment, conducted some decades ago, simulated conditions on the early earth in a beaker; an electric spark in an atmosphere of water, oxygen, CO2 and ammonia, produced an abundance of amino acids.
Looking over this chemical alphabet, one sees that they are the simplest combinations of the most common, most reactive elements present on early earth. Nitrogen is the most abundant, most reactive electron donor while oxygen is the most abundant, most reactive electron receptor. Carbon, meanwhile, is like a bisexual chemical slut – it can swing either way, and it bonds with just about anything. In short, the building blocks of life turn out to be just what you would expect, the simplest possible combinations of light elements. This bodes well for the theory of natural selection, extended to the chemical realm.
mad cow disease
Interestingly, prions, the infectious proteins responsible for “mad cow disease” (bovine spongiform encephalopathy), are non-DNA entities (unlike viruses and bacteria). Fragments of harmless proteins, these “rogue” proteins assume a new conformation and alter existing neuronal proteins, causing tissue damage. This is a radically alien way of conducting chemical commerce, as one might find on another planet or galaxy, as in that old Star Trek episode with the giant extragalactic space amoeba!


I have counted the number of named cytochrome P450s as of Jan. 18, 2004. There are 1277 animal sequences, 1098 plant sequences, 207 lower eukaryote sequences and 461 bacterial sequences named. That is a total of 3043 different sequences. (Note 455 are in rice) There are many more that are not yet named, such as 150 in the white rot genome and the two Ciona genomes will have about 60-90 each. These should all be named later this year. The total is 3043 on Jan. 19, 2004. for a list of these sequences see P450 Sequence List A second list giving just one member of each subfamily has 814 entries. A third list with only one member of each family has 368 families, after allowing for CYP51 in each group and CYP97 in lower eukaryotes and plants.

A BLAST server has been set up on a RedHat Linux machine to allow blast searching of selected P450 sets. The first set available is all the Arabidopsis P450s, 273 named genes and 16 more unnamed fragments that have not been designated because I do not know if they are really different from the named genes. We plan to add more P450 sets in the next few days and weeks. Only BLASTP works now since this is a protein database. The server address is http:/ GO THERE NOW


A link to Comparative genomics of rice and Arabidopsis. Analysis of 727 Cytochrome P450 genes and pseudogenes from a monocot and a dicot. Plant Physiology 135, 756-772 2004

A link to Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes Pharmacogenetics 14, 1-18 2004

A pdf version of Cytochrome P450 and the Individuality of Species. Archives Biochem. Biophys. 369, 1-10 1999

A pdf version of Comparison of P450s from Human and Fugu. Archives Biochem. Biophys. 409, 18-24 2003

A pdf version of Metazoan Cytochrome P450 Evolution. Comparative Biochem. Physiol. Part C 121, 15-22 1998

A pdf version of On the Topology of Vertebrate Cytochrome P450 Proteins. JBC 263, 6038-6050 1988

A link to P450 functions in plants an extensive listing with references. From the Plant Biotechnology Institute, National Research Council, Saskatoon, Saskatchewan CANADA

Neurotransmitters are small molecules that ferry information from the end of one nerve to the “beginning” of another by activating a large molecule at the far end of the synapse called a receptor. Other receptors exist presynaptically which modulate neurotransmitter release. Although there are in all likelihood hundreds of endogenous compounds that act in the CNS, it is still instructive to study the few that dominate our current understanding.
Other factors besides neurotransmitters which influence nerve function are the behavior of ion gates, G-peptides, and second messengers.

Acetylcholine was the first neurotransmitter discovered. Acetylcholine neurons convey sensory information to the brain and control muscular tension, including peristalsis. Cholinergic neurons are also present in the central nervous system (CNS).
Aspartic and glutamic acids ionize to the excitatory forms aspartate and glutamate. Aspartate and glutamate neurons occur in the CNS in hierarchical systems. These systems transport information “upward” to centers of consciousness in the cerebrum, serving an integrative function.
GABA is the most important inhibitory neurotransmitter in the CNS. It serves as a “brake” against excitatory systems such as glutamate and aspartate by gating calcium ions into the interior of nerve cells, reducing the likelihood of a positive internal action potential. Glycine is another important inhibitory amino acid. These overall neutrally-charged amino acids are inhibitory while acidic ones such as glutamate/aspartate are excitatory.
GABA, glycine, glutamate and aspartate are four examples of a class of compounds known as amino acids. These molecules contain an amine group (-NH2) and a carboxylic acid group (-COOH), hence the name. In aqueous solution the acid end of the molecule ionizes to -COO- and the amine end to -NH3+. This ionized form, known as a zwitterion, accounts for the high water solubility of amino acids. Amino acids are used by the body for many functions other than neurotransmitters, most importantly as the building blocks for proteins.

The catecholamines [epinephrine (adrenalin), norepinephrine and dopamine] control so-called adrenergic systems in the CNS. Some of these neurons radiate from the limbic system (emotional centers) and discharge neurotransmitters in a diffuse manner into the frontal cortex, i.e. into broad areas of brain tissue as opposed to delivering the chemical to specific synapses. They thus account for “global vigilance” (staying awake), mood, fight or flight response, etc. In addition they act peripherally to modulate blood pressure and other functions. These compounds are in turn controlled by peptide compounds secreted from the hypothalamus and thyroid. Just prior to waking each morning, the brain secretes ACTH (adrenocorticotropic hormone) to stimulate adrenalin release from the adrenal gland in the abdomen.
Serotonin is the primary inhibitory neurotransmitter modulating the excitatory catecholamine systems in the CNS. Serotonin neurons control memory, mood, sex drive, etc. The compound has many other functions including allergic response, and regulation of vasotension, especially in the meninges and other brain tissue. It is most highly concentrated in the gut. Melatonin, synthesized biogenically from serotonin, sets circadian rhythms, i.e. sleep cycles.
Histamine mediates allergic response and is concentrated in mast cells, whose main function is to detect trauma and release histamine and cotransmitters (leukotrienes, ATP). Another primary function of histamine is to regulate secretion of gastric acid.
Adenosine is a nucleotide, a neurotransmitter, and also a precursor to cAMP, a ubiquitous second-messenger system. Second messenger systems chemically link the activation of a post-synaptic receptor on the “beginning” (dendrite) of a neuron to the firing of voltage-dependent channels along the nerve fiber, propagating the digital information pulse. The mechanism of the IP3/DAG second-messenger system is shown on the phospholipids page.
neurotransmitter synthesis & degradation
The body synthesizes neurotransmitters from the nutrients in foods using complex catalytic molecules called enzymes. These enzymes are extremely selective “hands” which bend specific molecules or substrates and strain them, raising the (negative) energy of their bonds so they can react more efficiently at body temperature. Without these enzymes the reactions of life would proceed exceedingly slowly. After release into the synapse, the active neurotransmitters bind and detach from receptors at a given rate. Free neurotransmitter molecules must be cleaned up to return the synapse to the untriggered state. The two major mechanisms responsible for this housecleaning duty are reuptake (into presynaptic storage vesicles) and degradation.
Shown below are metabolic synthetic and degradative pathways for the major neurotransmitter systems. In many cases several pathways exist for producing a given product from a given reactant. This redundancy protects the nervous system from selective enzyme inhibition or insufficiency. Which path is taken depends on the relative activity and abundance of the given enzymes as well as the disposition of the enzymes and the relative abundance of reactants and products.
An interesting parallel exists between hormones utilized by animal and plant cells; in mny cases the same or similar hormones are used, though often for entirely different purposes. Thus tryptophan is used by animal neurons to syunthesize neurotransmitters like serotonin for, while plant cells synthesize auxin, which is used to regulate phototropic growth (i.e. the side of a plant which receives the most light secretes auxin longitudinally to cause growth in other areas, lower on the stem, towards the light).
glutamate & GABA

Just as some compounds inhibit neurotransmitter degradation by binding to and inactivating the pertinent enzymes, other compounds inhibit formation of neurotransmitters by similar mechanisms. P-chloroamphetamine and p-chlorophenylalanine are two compounds which inhibit serotonin synthesis. Alpha-methyl-m-tyrosine inhibits catecholamine synthesis.



Approvable Original New Drug Applications

An approvable letter indicates that FDA is prepared to approve the application upon the satisfaction of conditions specified in the approvable letter. Drug products which are the subject of approvable letters may not be legally marketed until the firm has satisfied the identified deficiencies, as well as any other requirements that may be imposed by FDA, and has been notified in writing that the application has been approved. Further information on approvable NDAs is not subject to Freedom of Information (FOI) release until applications are approved.

Original Abbreviated and 505(b)(2) New Drug Applications with Tentative Approval

A tentative approval indicates that FDA has given an abbreviated new drug application (ANDA) or 505(b)(2) application provisional approval under the terms of the Drug Price Competition and Patent Term Restoration Act. Such drug products that are the subjects of tentative approvals may not be legally marketed until the market exclusivity and/or patent term of the listed reference drug product has expired. Final approval is also contingent upon conditions and information available to FDA remaining acceptable. When the application receives final approval, the product may be legally marketed. The effective approval date will be listed in this publication and in the ” Approved Drug Products with Therapeutic Equivalence Evaluations” list published by FDA. Additional information on these applications will become available to the public when the applications receive final approval. Notes


FDA classifies investigational new drug applications (INDs) and new drug applications (NDAs) to assign review priority on the basis of the drug’s chemical type and potential benefit:
Chemical Type (CHE)

1. New molecular entity, or NME: An active ingredient that has never been marketed in this country.

2. New derivative: A chemical derived from an active ingredient already marketed (a “parent” drug).

3. New formulation: A new dosage form or new formulation of an active ingredient already on the market.

4. New combination: A drug that contains two or more compounds, the combination of which has not been marketed together in a product.

5. Already marketed drug product but a new manufacturer: A product that duplicates another firm’s already marketed drug product: same active ingredient, formulation, or combination.

6. Already marketed drug product, but a new use: A new use for a drug product already marketed by a different firm.

7. Drug already legally marketed without an approved NDA

1 – First post-1962 applications for products marketed prior to 1938
2 – First applications for DESI-related products first marketed between 1938 and 1962 without NDAs
3 – First applications for DESI-related products first marketed after 1962 without NDAs – The indications can be the same or different from the legally marketed product

Effectiveness Supplement Code Definitions

SE1 A new indication or a significant modification of an existing indication, including removal of a major limitation to use, such as second line status.

SE2 A new dosage regimen, including an increase or decrease in daily dosage, or a change in frequency of administration.

SE3 A new route of administration.

SE4 A comparative efficacy claim naming another drug, including a comparative pharmacokinetic claim.

SE5 A change in sections other than the INDICATIONS AND USAGE section that would significantly alter the patient population to be treated, such as addition of pediatric use and/or dosing information or geriatric use and/or dosing information.

SE6 An Rx-to-OTC switch. Treatment Potential (TP)

P-Priority review drug: A drug that appears to represent an advance over available therapy

S-Standard review drug: A drug that appears to have therapeutic qualities similar to those of an already marketed drug.

Other Designations (may apply simultaneously)

AA AIDS drug: A drug indicated for treating AIDS or other HIV related disease.

E Subpart E drug: A drug developed or evaluated under special procedures for drugs to treat lifethreatening or severely debilitating illnesses. (The name refers to Title 21 of the Code of Federal Regulations, Part 312, Subpart E, which governs this classification. Also see, “The Evolution of U.S. Drug Law,” page 26 of the booklet, FDA Consumer IconFrom Test Tube to Patient: NEW DRUG DEVELOPMENT IN THE UNITED STATES.)

V Designated orphan drug: A drug for which the sponsor received orphan designation under the Orphan Drug Act. Such a sponsor is eligible for tax credits and exclusive marketing rights for the drug.