Definition and classification of vitamins
Vitamins represent a heterogeneous group of organic substances that the body, with a few exceptions, is unable to synthesize and thus must be obtained through diet. Different organisms differ in their capacity to synthesize various vitamins. That is why, what counts as a vitamin for humans must not be essential for other animal species. Apart from diet, other important source of some types of vitamins (e.g. K or biotin) are bacteria colonizing our largeintestine.
Identical vitamins often occur in the form of multiple compounds known as vitamers, which differ from each other in structure (for example in having different substituents or functional groups) or function (e.g. vitamers of vitamin A – retinol, retinal and retinoic acid).
In general, vitamins can be divided according to the polarity of their molecule (affecting the solubility in water) into two groups:
1) Water soluble vitamins
These vitamins have hydrophilic character, but apart from it, from the chemical point of view, they do resemble each other only very slightly. Their absorption is easier compared to the fat-soluble vitamins and the do not require any special blood transport molecule. When taken in excess, they can easily be excreted through urine without any risk of overdose. This group includes B group vitamins and vitamin C.
2) Fat-soluble vitamins
Altogether, fat-soluble vitamins are derivatives of isoprene and have a lipophilic character. Their absorption requires intact absorption of lipids and their transfer in blood takes place via lipoproteins (like other lipids) or via specific transport proteins, e.g. vitamin D binding protein or retinol binding protein. Lipophilic character enables their storage in adipose tissue (or more generally in all tissues rich in fat), where they may accumulate. On one hand it may lead to their toxicity when taken in large quantities, but on the other, the adipose tissue may act as their storage, and release them when necessary. This group involves vitamins A, E, D and K.
Some vitamins enter our bodies in the form of precursor molecules called provitamins. Provitamins do not show any biological activity, but within the body they are converted into the active molecules of vitamins. Examples include a pigment β-carotene, the provitamin of vitamin A.
Function and pathology of vitamins
Vitamins are usually required only in small amounts (in order of micro- or milligrams), but they play an irreplaceable function within the body. Many vitamins act as enzyme cofactorsand participate in the enzyme-catalyzed reactions of metabolic pathways. Some vitamins are antioxidants and protect cellular structures against the oxidative stress.
Vitamin deficiency, which can occur for various reasons (inadequate intake of vitamins in diet, impaired intestinal absorption or metabolism of provitamins), may lead to hypovitaminosis or, in extreme cases, avitaminosis. Clinical manifestations differ (depending on the extent of deficiency or the type of the missing vitamin) – e.g. beriberi disease (thiamine deficiency) or scurvy (vitamin C deficiency). Pathological conditions may rarely develop due to an excess intake of some vitamins as well. They concern mainly fat-soluble vitamins, most often vitamin A and D and are termed hypervitaminosis.
Water soluble vitamins
Vitamin B1 (thiamine)
The structure of vitamin B1 contains substituted thiazole nuclei and pyrimidine. Biologically active form is called thiamine pyrophosphate (TPP, thiamine diphosphate) and its formation involves a special transferase located in brain and liver tissue.
Thiamine diphosphate is a cofactor of reactions that involve a transfer of an active aldehyderesidue. Such reactions are for example an oxidative decarboxylation of α-keto acids, where it participates in forming a multienzyme complexes (e.g. pyruvate dehydrogenase complex). Second group of reactions with the transfer of aldehyde residue, where thiamine plays an important part, the so-called transketolation reaction, occurs for example in the pentose cycle.
Thiamine is found in large quantities in the outer layers of the coating covering cereal grains, in yeast (which generally contain vitamins of B group), legumes, pork meat or milk. On the other hand, white bread (until it is not fortified) or peeled polished rise are low in its content. The recommended daily dose of thiamine is around 1.1 mg.
When eating thiamine deficient diet (for example containing processed cereal grains with the coating removed) a disease called beriberi develops. Beriberi is characterized by an impaired saccharide and amino acids metabolism and its symptoms include peripheral myopathies, fatigue and anorexia, later joined by edema, cardiovascular, neurological and muscle disorders. In the past, beriberi occurred extensively in Southeast and East Asia, where de-husked rice had served as the main food source.
Chronic alcoholics can develop a neurological condition known as Wernicke’sencephalopathy, after years of alcohol abuse, also caused by the vitamin deficiency.
Vitamin B2 (riboflavin)
Chemical structure of riboflavin (from Latin flavus – yellow) contains alcohol called ribitolconnected to a heterocyclic core.
Our bodies phosphorylate and transform riboflavin to one of its active forms – flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD). They both form prostheticgroups of a set of oxidoreductases called flavoproteins. One of the most well known enzymes are part of the respiratory chain – NADH- dehydrogenase or succinate dehydrogenase.
Riboflavin is present in yeast, liver, kidneys, eggs or milk. The recommended daily intake is around 1.4mg.
Riboflavin deficiency fortunately does not cause significant problems. Usually only uncharacteristic symptoms, typical for deficiency of other vitamins of B group as well, occur – e.g. inflammations in the oral cavity (lips, tongue, corners of the mouth), skin changes or delayed wounds healing.
Vitamin B3 (niacin)
Vitamin B3 is a collective term for two compounds: nicotinic acid and nicotinamide. Niacin used to be termed vitamin PP (pellagra- preventive).
Biologically active forms of niacin are nicotinamide adenine dinucleotide (NAD+) and its phosphorylated derivative – nicotinamide adenine dinucleotide phosphate (NADP+).
Both are ubiquitous, acting as cytosolic and mitochondrial coenzymes of oxidation-reduction enzymes. NAD+ is generally a cofactor of oxidoreductases in oxidative pathways (for example Krebs cycle), NADPH is a part of dehydrogenases or reductases participating in so-called reductive syntheses – occurring for example in the fatty-acid metabolism or pentose cycle.
Acting through special G-protein coupled receptors, expressed mainly in the adipose tissue (but present in liver tissue or immune cells as well), the nicotinic acid inhibits lipolysis and release of free fatty acids from the adipose tissue. This process reduces their availability in the synthesis of lipoproteins in liver and thus the plasmatic levels of VLDL (and consequently LDL and total cholesterol) decrease. This effect has not been observed in nicotinamide.)
Good sources of niacin are liver, fish (or other meat), yeast or bran. Due to our body’s abilityto synthesize niacin, up to some extent, using the essential amino acid tryptophan, symptoms of its deficiency only occur in the absence of both of these nutrients in diet. The recommended daily dose of this vitamin is quite high – around 16mg.
Shortage of niacin leads to a disease called pellagra, the “three D disease”, characterized by a triad of symptoms: dermatitis, diarrhea and dementia.
Vitamin B5 (pantothenic acid)
Vitamin B5 is made of six-carbon branched hydroxy acid called pantoic acid bound to β-alanine. The name pantothenic acid is derived from greek pantothen – from everywhere. Vitamin B5 is indeed present in many foods of plant or animal origin (see below).
Pantothenate, the precursor molecule of coenzyme A, acts within the metabolic pathways as a carrier of acyl residues. Among the most important reactions it participates in are Krebs cycle, synthesis and degradation of fatty acids or cholesterol synthesis. The importance of vitamin B5 is therefore quite considerable.
As it already has been mentioned above, pantothenic acid is present in many kinds of foodstuff, including legumes, whole grain products, meat, offal or yeast. That is why we encounter its deficiency, characterized by skin disorders and hair follicle atrophy, only rarely. The recommended daily intake of 6-10 mg per day is not difficult to achieve.
Vitamin B6 (pyridoxine)
Vitamin B6 includes three related pyridine derivatives with the same biological function – pyridoxine (pyridoxol), pyridoxal and pyridoxamine.
All three of them have to be transformed and phosphorylated (with the help of an enzyme pyridoxal kinase, present in most of body tissues) into pyridoxal-5-phosphate (PLP), the biologically active form of vitamin B6.
Pyridoxal phosphate functions as a cofactor of many enzymes, participating in the metabolism of amino acids, for example amino transferases (transaminases) or decarboxylases. In all of these reactions, the aldehyde groups of pyridoxal phosphate bind to the amino group of the amino acids forming so-called Schiffs base.
Other enzyme requiring the presence of pyridoxal phosphate (acting as its cofactor) is glycogen phosphorylase, enzyme cleaving the molecules of glycogen.
Vitamin B6 is present in many animal and plant products. Examples include liver, meat (including fish), whole grain products, nuts, vegetables (potatoes, cabbage, carrots), bananas or avocados. The recommended daily dose is about 2 mg.
Isolated vitamin B6 deficiency is rare, more often it is related to the deficiencies of other B group vitamins. The symptoms of deficit are therefore more or less symptoms of general deficiency of group B vitamins: dermatitis, mucositis (mainly oral) and CNS disorders. Disorders of tryptophan metabolism are also common.
Shortage may result from an intake of certain medication as well. For example antitubercular drug isoniazid forms complexes with vitamin B6 and thus disrupts its function.