Lecture : MSc. zainab ali Water soluble vitamin

Vitamins Vitamins may be defined as organic compounds occurring in small quantities in different natural foods and necessary for growth and maintenance of good health in human beings and in experimental animals. Vitamins are essential food factors, which are required for the proper utilization of the proximate principles of food like carbohydrates, lipids and proteins.

Vitamins are classified into two groups on the basis of their solubilities: fat soluble and water soluble.

Water-soluble vitaminsThe water-soluble vitamins are:_ the B complex:

– thiamine (B1),– ribofl avin (B2),– nicotinamide (niacin),– pyridoxine (B6),– folate (pteroylglutamate),– the vitamin B12 complex (cobalamins),– biotin and pantothenate,

_ ascorbate (vitamin C).

In this lecture we will review the source, function, and abnormalities status of each one

Thiamine (B1)

Humans cannot synthesize thiamine. It is found in many dietary components; Aleurone layer of cereals (food grains) is a rich source of thiamine. Therefore, whole wheat flour and unpolished hand pound rice have better nutritive value than completely polished refined foods. When the grains are polished, aleurone layer is usually removed. Yeast is also a very good

1. source. Thiamine is partially destroyed by heat.wheat germ, oatmeal andyeast are particularly rich sources.

2. Function : Thiamine is a component of thiamine pyrophosphate, which is an essential cofactor for the following enzymes :

Pyruvate dehydrogenase: decarboxylation of alfa-keto acid ; one such reaction is the conversion of pyruvate to acetyl coenzyme A. In thiamine deficiency, pyruvate cannot be metabolized and accumulates in the blood.

transketolase in the pentose–phosphate pathway.

3. Clinical effects of thiamine deficiency : Adequate amounts are present in a normal diet and deficiency is most common

1- Beriberi: It is a Singhalese word, meaning “weakness”. The early symptoms are anorexia, dyspepsia, heaviness and weakness. Subjects feel weak and get easily exhausted.

Wet beriberi: Here cardiovascular manifestations are prominent. Edema of legs, face, trunk and serous cavities are the main features , death occurs due to heart failure.

Dry beriberi: In this condition, CNS manifestations are the major features.

Infantile beriberi: It occurs in infants born to mothers suffering from thiamine deficiency. Restlessness and sleeplessness are observed.

cerebral beriberi or Wernicke-Korsakoff syndrome: Clinical features are those of encephalopathy (ophthalmoplegia, nystagmus, cerebellar ataxia) plus psychosis. It is seen only when the nutritional status is severely affected.

4. Polyneuritis: It is common in chronic alcoholics. Alcohol utilization needs large doses of thiamine. Alcohol inhibits intestinal absorption of thiamine, leading to thiamine deficiency. Polyneuritis may also be associated with pregnancy and old age. Thiamine deficiency in alcoholism may cause impairment of conversion of pyruvate to acetyl CoA. The result is increased plasma concentration of pyruvate and lactate, leading to lactic acidosis.

4- Laboratory diagnosis of thiamine deficiency1- the estimation of erythrocyte transketolase activity .( Reduced activity)2- Other tests may be useful, including the measurement of both blood and urinary

thiamine concentrations, 3- a raised blood pyruvate concentration is suggestive as is a lactic acidosis

Riboflavin (B2)1- Sources Riboflavin is found in large amounts in yeasts and germinating plants such as peas and beans, and in smaller amounts in fish, poultry and meat.

2- Functions it is incorporated in the form of - flavine mononucleotide (FMN) - flavine adenine dinucleotide (FAD).

Both FMN and FAD are reversible electron carriers in biological oxidation systems, which are, in turn, oxidized by cytochromes.

Riboflavin Deficiency(ariboflavinosis) 1- Causes: Natural deficiency of riboflavin is uncommon, because riboflavin is

synthesized by the intestinal flora. Riboflavin deficiency usually accompanies other deficiency diseases such as beriberi, pellagra and Kwashiorkor.

Manifestations: causes a rough, scaly skin, especially on the face, cheilosis (red, swollen, cracked lips), angular stomatitis and similar lesions at the mucocutaneous junctions of the anus and vagina (orogenital syndrome), and a swollen, tender, red tongue that is described as magenta coloured. Congestion of conjunctival blood vessels may be visible if the eye is examined with a slit lamp.

1- Laboratory diagnosis of riboflavin deficiency1- The finding of a low erythrocyte activity of glutathione reductase (Riboflavin acts

as a cofactor for this enzyme)2- A low urinary riboflavin concentration may also be a useful marker of deficiency.

The treatment for deficiency is to give riboflavin. Riboflavin excess is very rare.

Nicotinamide (niacin)

SourcesNicotinamide can be formed in the body from nicotinic acid. Both substances are plentiful in animal and plant foods, although much of that in plants is bound inan unabsorbable form. Some nicotinic acid can also be synthesized in humans from tryptophan. Probably both dietary and endogenous sources are necessary to provide enough nicotinamide for normal metabolism.

Functions1- Nicotinamide is the active constituent of nicotinamide adenine dinucleotide (NAD+)

and its phosphate (NADP+), which are important cofactors in oxidation–reduction reactions such as glycolysis and oxidative phosphorylation, and for many synthetic processes.

Not : Reduced NAD+ and NADP+ are, in turn, re-oxidized by flavoproteins, and the functions of riboflavin and nicotinamide are closely linked.

Clinical effects of nicotinamide deficiency1- Pellagra

Deficiency of niacin leads to the clinical condition called pellagra. Pellagra is an Italian word, meaning “rough skin”. Pellagra is caused by the deficiency of Tryptophan as well as Niacin. Pellagra is seen more in women; this may be because tryptophan metabolism is inhibited by estrogen metabolites. The symptoms of pellagra are Dermatitis, Diarrhea, Dementia:

Causes of nicotinamide deficiency

1- Dietary deficiency of nicotinamide2- Deficient synthesis: 3- Isoniazid (INH): It is an antituberculous drug, which inhibits pyridoxal phosphate

formation. Hence, there is block in conversion of tryptophan to NAD+.4- Hartnup disease: Tryptophan absorption from intestine is defective in this

congenital disease. Moreover, tryptophan is excreted in urine in large quantities. 5- Carcinoid syndrome: The tumor utilizes major portion of available tryptophan for

synthesis of

Laboratory diagnosis of nicotinamide deficiencymeasuring urinary N-methylnicotinamide concentration, which is low in deficiency.

Pyridoxine (B6)Pyridoxine (Vitamin B6)StructureVitamin B6 consists of a mixture of three different closely related pyridine derivatives namely, all the three have equal vitamin activity, as they can be interconverted in the body:

1. Pyridoxine2. Pyridoxal3. Pyridoxamine.

Active Form of Vitamin B6Pyridoxal phosphate (PLP) is the active form of vitamin B6 . PLP is formed from phosphorylation of all three forms of vitamin B6.

Sources• Pyridoxine occurs mainly in plants, whereas pyridoxal and pyridoxamine are present mainly in animal products.• Major dietary sources of vitamin B6 are yeast, unrefined cereals, pulses, meat, poultry fish, potatoes and vegetables.• Dairy products and grains contribute lesser amounts.

Functions• Active form of vitamin B6, pyridoxal phosphate (PLP) acts as coenzyme in large number of reactions of amino acid metabolism. For example:– Transamination– Decarboxylation– Nonoxidative deamination– Trans-sulfuration– Condensation reactions of amino acids

Deficiency Manifestations As pyridoxine occurs in most foods, the dietary deficiency of vitamin B6 is rare.

Neurological Manifestations; Dermatological Manifestations; Hematological Manifestations

Not Doses over 100 mg may lead to sensory neuropathy Further excess is manifested by imbalance, numbness, muscle weakness and nerve damage.

Folic Acid

Active Form of Folic Acid

Tetrahydrofolate (THF) is the active form of folic acid. Folate is enzymatically reduced in a two-stage process in tissues to yield the dihydro and then tetrahydrofolate, which requires vitamin C.

function THF acts as a carrier of one carbon units. The one carbon units are

Deficiency ManifestationsFolate deficiency frequently occurs particularly in pregnant women and in alcoholics. Clinical symptoms of folic acid deficiency include:

• Megaloblastic or macrocytic anemiaThe deficiency of folic acid leads to

1- impairment of synthesis of DNA, 2- impairs the maturation of erythrocytes. 3- Accumulation and excretion of formiminoglutamate FIGLU in the urine:

Folate deficiency blocks the last step of histidine catabolism, due to lack of Tetrahydrofuran (THF) and this results in accumulation of FIGLU in body, which leads to increased excretion of FIGLU in urine

Hyperhomocysteinemia: Due to folic acid deficiency the methylation of homocysteine to methionine is impaired which leads to hyperhomocysteinemia. Increased level of homocystein is a risk factor for cardiovascular disease.

Neural tube defect in fetus: Since, folate is required for the formation of neural tube in early stage of gestation, the folate deficiency during early stage of pregnancy increases the risk of neural tube defect

Biotin

Biotin was known formerly as vitamin H. Biotin is an imidazole derivative It consists of a tetrahydrothiophene ring bound to an imidazole ring and a valeric acid side chain

Sources• It is widely distributed in foods.• Liver, kidneys, vegetables and egg yolk are the important sources of biotin.• Biotin is also synthesized by intestinal bacteria.

Active Form of BiotinEnzyme-bound biotin, biocytin is an active form of biotin. Biotin is covalently bound to ε-amino group of lysine of an enzyme to form biocytin.

Functions Biotin is a coenzyme of carboxylase reactions, where it is a carrier of CO2.

Deficiency Manifestation

• Since biotin is widely distributed in plant and animal foods and intestinal bacterial flora supply adequate amounts of biotin, the natural deficiency of biotin is not well characterized in humans.

Use of antibiotics, that inhibit the growth of intestinal bacteria, eliminates this source of biotin and leads to deficiency of biotin.

Pantothenic Acid (Vitamin B5)

The name pantothenic acid is derived from the Greek word ‘pantothene,’ meaning from “everywhere” and gives an indication of the wide distribution of the vitamin in foods.

StructurePantothenic acid is formed by a combination of pantoic acid and β-alanine .

Active form : Active forms of pantothenic acid are:• Coenzyme-A (CoA-SH)• Acyl carrier protein (ACP).

Source : Eggs, liver, yeast, wheat germs, cereals, etc. are important sources of pantothenic acid, although the vitamin is widely distributed.

Functions• The thiol (-SH) group of CoA-SH and ACP acts as a carrier of acyl groups.• Coenzyme-A participates in reactions concerned with:– Reactions of citric acid cycle– Fatty acid synthesis and oxidation– Synthesis of cholesterol– Utilization of ketone bodies.• ACP participate in reactions concerned with fatty acid synthesis.

Deficiency ManifestationsNo clearcut case of pantothenic acid deficiency has been reported (becuase the substance is widely distributed in foods) except in malnourished prisoners of war

Cobalamin VIT B12

Thus, cobalamin exists in three forms that differ in the nature of the chemical group attached to cobalt.

1- Cynocobalamin is the commercial available form of vitamin B12.

2- Methylcobalamin3- Deoxyadenosylcobalamin

Active form of Vitamin B12

The active coenzyme forms of vitamin B12 are:• Methylcobalamin• Deoxyadenosylcobalamin

Sources• Dietary sources of vitamin B12 are of animal origin and include meat, eggs, milk, dairy products, fish, poultry, etc.• Vitamin B12 is absent in plant foods. • Humans obtain small amounts of vitamin B12 from their intestinal flora.

Vitamin B12 is the only water soluble vitamin that is stored in significant amounts in the liver.

FunctionsThere are only two human enzyme systems that are known to require vitamin B12 coenzyme.

1. Isomerization of methylmalonyl-CoA to succinyl-CoA2. 2. Conversion of homocysteine to methionine

Deficiency ManifestationsDeficiency may arise due to decreased absorption or decreased dietary intake. Dietary deficiency is seen in strict vegetarians, since the vitamin found only in foods of animal origin or in microorganisms. Deficiency of vitamin B12 leads to:• Pernicious anemia• Megaloblastic anemia• Methylmalonic aciduria• Neuropathy.

Ascorbate (vitamin C)

Vitamin C is also known as ascorbic acid It is a sixcarbon sugar derivative Most animals cansynthesize ascorbic acid. But humans cannot synthesize ascorbic acid, due to lack of the enzyme gluconolactone oxidase which is required for the synthesis of ascorbic acid. Thus, humans have a dietary requirement of ascorbic acid.

Active Form of Ascorbic AcidAscorbic acid itself is an active form.

Sources• The main dietary sources of vitamin C are leafy vegetables and fruits, especially citrus fruits, strawberries, tomatoes, spinach and potatoes.• Cereals contain no vitamin C.• Animal tissues and dairy products are very poor sources.

FunctionsAscorbic acid functions as a reducing agent in many metabolic processes as follows:Collagen biosynthesis

Steroid synthesis: In adrenal cortex, vitamin C is involved in the hydroxylation reactions of steroids , Adrenaline synthesis; Carnitine synthesis: Bile acid formation

Degradation of tyrosine, Folate metabolism, Absorption of ironAscorbic acid is a water soluble antioxidant

Deficiency ManifestationDeficiency of ascorbic acid causes scurvy. Symptoms of scurvy are related to deficient collagen formation (Refer functions of vitamin C). These include:

Spongy, swollen, bleeding gums, loosening of teeth• Abnormal bone development and osteoporosis• Poor wound healing• Anemia due to impaired erythropoiesis• Easy bruising and bleeding due to fragile capillaries

ToxicityVitamin C can be taken in doses up to 2–3 g/day without undesirable effects. Above these levels, however, it cannot be absorbed from the intestine and can cause severe diarrhea and deposition of oxalate stones in kidneys.