The following points highlight the top six types of water soluble vitamins. The types are: 1. Ascorbic Acid (Vitamin C) 2. Thiamine (Vitamin B1) 3. Riboflavin (Vitamin B2) 4. Niacin (Nicotinic Acid) (Vitamin B3)5. Pyridoxine (Vitamin B6) 6. Pantothenic Acid (Vitamin B5).
Water Soluble Vitamins: Type # 1. Ascorbic Acid (Vitamin C):
a. The isolation of vitamin C was carried out by Zilva during 1917-1927. He obtained the highly potent substance and noted its reducing properties.
b. In 1928, Szent-Gyorgy isolated an acid with strong reducing properties from cabbages, adrenal glands and oranges. He called it Hexuronic acid.
c. In 1931, Waugh and King isolated vitamin C in a crystalline form from lemon juice.
d. In 1933, vitamin C was named ascorbic acid owing to its antiscorbutic properties.
a. Haworth and co-workers in 1933 established the chemical structure of ascorbic acid.
b. The synthesis of vitamin C was reported in 1933 by Haworth and co-workers in England and Reichstein and co-workers in Switzerland.
c. The chemical structures of L-ascorbic acid and L-dehydro ascorbic acid are given below.
d. The structure of L-ascorbic acid shows that it is a derivative of hexose called L- gulose.
a. Ascorbic acid is a white crystalline water- soluble substance with sour taste.
b. It is chemically an enediol-lactone which is oxidized to dehydroascorbic acid (ascorbone). Both these forms are biologically active.
c. D-ascorbic acid does not possess any antiscorbutic activities.
d. The oxidation of ascorbic acid is catalyzed by copper and silver ions and the oxidation is faster at higher temperatures, e.g., during cooking of foods.
e. It is a powerful reducing agent which can reduce Fehling’s solution in the cold.
f. It can reduce 2, 6-di-chloro-phenol-indophenol to the colourless leuco base.
g. It is easily destroyed by cooking.
h. It is stable below pH 6.8 at room temperature but readily oxidized in an alkaline medium.
Absorption and Storage:
a. Ascorbic acid is readily absorbed from the small intestine, peritoneum and subcutaneous tissues.
b. It passes through the portal vein to the general circulation and to all tissues.
c. It is supplied to the fetus from the maternal circulation passing the placental barrier readily. The placenta is also able to concentrate this vitamin.
d. It is not stored in any particular organ and is distributed throughout the body.
e. Each organ or tissue has an optimal saturation level of ascorbic acid. Excessive intake of ascorbic acid does not increase the saturation level but the excess is excreted in the urine.
Normal Concentration in Blood Plasma:
0.4-1.5 mg/100 ml of blood plasma.
In erythrocytes 1½ times of that of plasma, and in white blood cells and platelets 20-40 times of that of plasma.
a. Since it is very sensitive to reversible oxidation (ascorbic acid ⇋ dehydroascorbic acid) it is involved in the oxidation-reduction reactions of the cell.
b. It is involved in the conversion of folic acid to folinic acid (citrovorum factor).
c. It is involved in the hydroxylation of steroids in the adrenal cortex.
d. It is required in the metabolism of tyrosine and phenylalanine and also in tryptophan.
e. It is required for the absorption of iron and incorporation of plasma iron in ferritin.
f. It is involved in the formation of norepinephrine.
g. It is essential for the normal regulation of the colloidal condition of intercellular substances including the fibrils and collagen of connective tissue, osteoid tissue, dentine, the intercellular ‘cement substance’ of the capillaries.
h. It is concerned in the hydroxylation of proline and hydroxyproline which is an important constituent of collagen.
i. It has an inhibitory effect on the hyaluronidase-hyaluronic acid system.
j. High doses of vitamin C prevent the common cold or reduce the duration of its symptoms.
Severe ascorbic acid deficiency produces scurvy. The signs of this deficiency are entirely confined to supporting tissues of mesenchymal origin (bone, dentine, cartilage, and connective tissue).
Scurvy is characterized by failure in the formation and maintenance of intercellular materials which causes typical symptoms such as:
a. Internal haemorrhages.
b. Loosening of the teeth.
c. Poor healing of wounds.
d. Swelling of long bones.
e. Easy fracturability of bones.
f. Swelling, sponginess, tenderness and bleeding of gums.
h. Susceptibility to infections.
i. General weakness.
(a) A dose of 250 mg by mouth 3 times daily may saturate the tissues quickly.
(b) Sometimes folic acids are given if the patient is anemic iron.
(c) No patient dies of scurvy with adequate treatment and recovery is usually rapid and complete.
(d) Old or solitary people who do not eat fruit and vegetables should be advised to take 50 mg ascorbic acid tablets daily.
(e) The requirement of vitamin C is increased in case of trauma, surgery and burns, infections, smoking and certain drugs— adrenocortical steroids, aspirin, indomethacin and tetracycline. So patients affected by these require more than the recommended intake.
(a) The most important side-effect of large doses is to exacerbate hemochromatosis or other iron storage disease which is not a problem for the great majority of people.
(b) Oxalate is a metabolite of ascorbic acid and urinary oxalate is likely to increase with large intakes of vitamin C. It may be related to urinary tract stones. Hence, it is wise to avoid excessive vitamin C intake.
Water Soluble Vitamins: Type # 2. Thiamine (Vitamin B1):
a. In 1885, Takaki prevented the occurrence of beriberi in the Japanese navy by altering the diet.
b. In 1897, Eijkmann produced polyneuritis in fowls by feeding them a diet consisting of washed polished rice and showed that the birds recovered after the administration of extracts of rice polishing’s.
c. In 1926, Jansen and Donath isolated vitamin B1 in crystalline form from rice polishing’s.
d. In 1931, Windaus and co-workers isolated vitamin B1 in crystalline form from yeast and established its empirical formula.
e. In 1934, Williams and co-workers and in 1933 and 1935 Peters and co-workers made improvements in the methods of isolation of vitamin B1.
a. Williams and co-workers in 1936 established the chemical structure of thiamine.
The chemical structure is given (Fig. 15.13):
b. Vitamin B1 contains a pyrimidine and thiazole ring and they are linked by methylene bridge.
c. One compound: 2, 5 dimethyl 6 amino-pyrimidine.
Another compound: 4 methyl 5 hydroxy ethylthiazole.
a. Thiamine is readily soluble in water.
b. It is stable in acid medium.
c. It is destroyed when autoclaved at 120°C for 30 minutes.
d. It is destroyed even at room temperature in an alkaline medium.
e. When it is dissolved in sodium bi-sulphite solution at pH 4.8 to 5.0 it is cleaved into pyrimidine half and thiazole half.
f. When oxidized with potassium ferricyanide in alkaline solution, it is converted into thiochrome which has a strong fluorescence in ultraviolet light.
Absorption and Storage:
Free thiamine is readily absorbed from the small intestine but not TPP. Excess thiamine administered is not stored in the tissues. A part of the excess thiamine is excreted in urine and some of it is destroyed.
It is difficult to fix a single requirement of vitamin B1. The requirement is increased when metabolism is elevated as in fever, hyperthyroidism, increased muscular activity, pregnancy and lactation.
Fat and protein reduce while carbohydrate increases the daily requirement of the vitamin. Some of the thiamine is synthesized by the bacteria in the intestine. Deficiencies of the vitamin occur not only by poor dietary intake but also in persons suffering from organic diseases.
Normal Concentration of Vitamin B1 in the Blood Plasma:
About 1 µg/100 ml. of blood plasma in free form.
a. Thiamine is essential for growth.
b. It is essential for maintaining the nerves in normal condition.
Thiamine is converted to its active form TPP (Thiamine pyrophosphate or diphosphate) by ATP- dependent thiamine pyro-phosphokinase which is present in brain and liver.
Thiamine pyrophosphate is a coenzyme in enzyme reactions in which an activated aldehyde unit is transferred.
There are two types of reactions:
a. An oxidative decarboxylation of α-keto acids (e.g., α-ketoglutarate, pyruvate and the α-keto analogs of leucine, isoleucine and valine).
b. Transketolase reactions (in pentose phosphate pathway)
All of these reactions are inhibited in thiamine deficiency.
Metabolic Role as a Coenzyme:
a. TPP is involved in oxidative decarboxylation of certain important intermediates in carbohydrate metabolism e.g., pyruvic acid and α-ketoglutaric acid, so it is referred to as co-carboxylase.
b. Acts as a coenzyme to the enzyme pyruvate dehydrogenase complex which converts pyruvic acid to acetyl-CoA (oxidative decarboxylation):
c. Acts as a coenzyme to α-ketoglutarate dehydrogenase complex and converts α-ketoglutarate to succinyl-CoA (oxidative decarboxylation):
d. TPP acts as a coenzyme with the enzyme transketolase in transketolation reaction in HMP shunt pathway:
e. Vitamin B1 is required in tryptophan metabolism for the activity of enzyme tryptophan pyrrolase.
f. Acts as a co-enzyme for mitochondrial branched chain α-ketoacid decarboxylase which catalyzes oxidative decarboxylations of branched chain α-ketoacids formed in the catabolism of valine, leucine, isoleucine.
It is a nutritional disorder i.e. thiamine deficiency.
Three forms of disease are:
(a) Wet beriberi:
(i) Oedema is the most prominent feature and develops rapidly in the legs, face etc.
(ii) Anorexia and dyspepsia are present.
(iii) The calf muscles are tense, slightly swollen and tender on pressure (pins and needles).
(iv) The pulse is fast.
(v) The apex beat of heart is displaced outwards.
(vi) Urine volume is diminished but there is no albuminuria.
(b) Dry beriberi:
(i) The essential feature is polyneuropathy.
(ii) The subject needs stick to stand and walk and finally becomes bedridden.
(iii) The concentrations of pyruvic acids and lactic acids are increased.
(iv) Transketolase activity of red cells is decreased.
(v) The muscles become wasted and weak and it is difficult to walk.
(c) Infantile beriberi:
(i) This occurs in breast-fed infants between 2nd to 5th months.
(ii) In acute form—Cardiac failure develops, the mother notices that infant is restless, cries a lot, is passing less urine, than normal. The infant may be cyanosed with dyspnoea and tachycardia and may die within 24 to 48 hours.
(iii) In chronic form—the main symptoms are due to gastrointestinal disturbances. There is constipation and vomiting. The child is fretful and sleeps poorly.
II. Wernicke’s encephalopathy is a condition associated with thiamine deficiency. It is frequently found in chronic alcoholics consuming little other food.
III. In the deficiency of vitamin B1, there is impaired conversion of pyruvate to acetyl- CoA. In case of high carbohydrate diet, there is increased plasma concentration of pyruvate and lactate which may cause life- threatening lactic acidosis.
(a) Treatment must be started as soon as the diagnosis is made in the deficiency of thiamine. Complete rest is most essential and 50 mg thiamine should be given intramuscularly for 3 days. Thereafter 10 mg 3 times a day should be continued by mouth until convalescence is established.
(b) Wernicke’s encephalopathy should be treated with 50 mg thiamine hydrochloride by slow intravenous injection followed by 50 mg intramuscularly daily for a week. Confusion, disorientation and ophthalmoplegia should respond within 2 to 3 days. The memory disorder takes longer to improve.
The prevention of Beriberi and Wernicke’s encephalopathy in Western countries is closely related to the control of alcoholism. Bread and other staple cereal foods are prescribed with thiamine in most industrial countries. In a chronic alcoholic, vitamin B complex tablets can at least prevent the complications of thiamine deficiency. Beriberi is much less common in Asia.
If the vitamin is taken in excessive amounts, the excess vitamin is promptly excreted in the urine. As a result, there is no evidence of toxicity.
Water Soluble Vitamins: Type # 3. Riboflavin (Vitamin B2):
a. As early as 1879 the water-soluble, yellow-green, fluorescent pigment in milk whey was noted. This substance was not isolated in pure form until 1932.
b. It was first isolated from milk, hence the earlier name lactoflavin.
c. It was shown to be a constituent of oxidative tissue-enzyme system and an essential growth factor for laboratory animals.
a. Kuhn, Karrer and co-workers (1934, 1935) accomplished the synthesis of riboflavin.
b. It contains an isoalloxazine nucleus. The chemical structure of it is given (Fig. 15.14).
c. It is water-soluble, heat-stable and sensitive to light.
d. The solution of vitamin B2, when exposed to ultraviolet light, emits a strong greenish yellow fluorescence.
e. On oxidation with ultraviolet rays or visible light, it undergoes irreversible decomposition.
f. It is rapidly destroyed when the solution is exposed to bright light.
g. Reducing agents such as stannous chloride and hydrosulphite convert it into a colourless compound without any fluorescence.
h. Riboflavin in alkaline solution when exposed to ultra-violet light is converted into lumiflavin which has a greenish yellow fluorescence in ultraviolet light.
Absorption and Storage:
The vitamin is phosphorylated in the intestinal mucosa during absorption. It is absorbed from the small intestine through the portal vein and is passed to all tissues being stored in the body. The major part is excreted in urine and a small part is metabolized in the body.
Normal Concentration in Blood Plasma:
2.5 to 4.0 µg/100 ml. of blood plasma.
a. Riboflavin is involved in the regulatory functions of some hormones connected with carbohydrate metabolism.
b. The free riboflavin present in retina is converted by light to a compound involved in stimulation of the optic nerve.
Biological active form:
a. FMN — Flavin mononucleotide (flavin ribityl PO4).
b. FAD — Flavin adenine dinucleotide (flavin ribityl-P-P ribose adenine).
The acidic properties given by phosphoric acid group influence their capacity for combining with proteins apo-enzyme forming flava protein (holoenzyme).
FP (holoenzyme) = FMN/FAD + Protein (co-enzyme) (apoenzyme)
FP may also unite with metals like Fe and Mo, thus forming metallo flavoproteins.
Riboflavin is converted into FMN by flavokinase during absorption in intestine.
Free riboflavin undergoes phosphorylation, a prerequisite for absorption (thiamine).
(a) It acts as a coenzyme for enzyme catalysed oxidation-reduction reaction.
(b) It is the component of aerobic dehydrogenase.
(c) This is one of the component of respiratory chain for the trans-part of electron:
a. Lips—Redness and shiny appearance of lips.
b. Cheilosis—Lesions at the mucocutaneous junction at the angles of mouth leading to painful fissures.
c. Tongue—Painful glossitis, the tongue assuming a red purple (magenta) colour.
d. Seborrheic dermatitis—Scaly, greasy, desquamation chiefly about the ears, nose and nasolabial folds.
e. Eyes—May lead to corneal vascularization and inflammation with cloudiness of cornea, watering, burning of eyes, photophobia and cataract.
In the deficiency of riboflavin, the therapeutic dose of riboflavin is 5 mg 3 times a day by mouth. It gives the patient’s urine a green fluorescence. Other B complex vitamins should also be given.
No toxic effect.
Water Soluble Vitamins: Type # 4. Niacin (Nicotinic Acid) (Vit. B3):
a. During 1922-1928 Goldberger and coworkers treated the disease pellagra in human beings and, in 1928, they showed that boiled yeast extract can cure pellagra. Hence, Goldberger named niacin as the Pellagra-Preventive (P-P) factor.
b. In 1937, three groups of workers independently reported that nicotinic acid was effective in curing Pellagra in human beings.
c. Niacin is not strictly a vitamin since it can be synthesized from the essential amino acid tryptophan. Most of the niacin in cereals is biologically unavailable which is discounted.
a. Niacin is pyridine 3-carboxylic acid. It occurs in tissues as niacin amide (nicotinamide). The chemical structures of both are given (Fig. 15.15).
b. It is soluble in water.
c. It is stable to heat and not destroyed by autoclaving at 120°C for 20 minutes in acid or alkaline medium.
d. Nicotinamide, when heated in a strong alkaline or acid solution, is converted into nicotinic acid.
e. Nicotinamide exists in human and animal tissues as coenzyme 1 (DPN, now called NAD) and coenzyme 11 (TPN, now called NADP).
Absorption and Storage:
a. Nicotinic acid and nicotinamide are absorbed from the intestine through the portal vein into the general circulation.
b. Excess nicotinic acid is not stored in the body.
c. The majority of the excess nicotinic acid is excreted in urine in the form of N- methylnicotinamide, 6-pyridone of N- methylnicotinamide, N-methyl nicotinic acid and the glycine conjugates of these methyl derivatives. Methylation takes place in the liver. Methionine is the principal source of these methyl groups.
d. Niacin in the form of niacytin present in maize is not absorbed unless the food is prepared with alkali (tortilla).
Normal Concentration of Niacin in the whole Blood:
0.5-0.8 mg./’ 00 ml. of whole blood.
a. Nicotinic acid is essential for the normal functioning of the skin, intestinal tract and the nervous system.
b. Lack of vitamin B2 and vitamin B6 causes deficiency of niacin due to the nonproduction from tryptophan.
c. Nicotinic acid (but not nicotinamide) is used therapeutically for lowering plasma cholesterol. This happens so due to the inhibition of the flux of FFA from adipose tissue which leads to less formation of the cholesterol bearing lipoproteins, VLDL and LDL.
(a) Nicotinic acid principally occurs as nicotinamide or niacin amide. This niacin amide is a component of two coenzymes NAD and NADP. This reduced form of NAD is di-hydro-nicotinamide adenine di-nucleotide (NADH) and that of NADP is di-hydro-nicotinamide adenine dinucleotide phosphate (NADPH).
(b) These coenzymes play an important role in metabolism by acting as hydrogen and electron transfer agents by means of reversible oxidation and reduction. Hence, the great importance of niacin in human nutrition as well as in the requirements of many other organisms including bacteria and yeast is stated.
The mechanism of transfer of hydrogen from a metabolite to oxidized NAD causing the oxidation of the metabolite and the formation of reduced NAD is shown in Fig. 15.16.
(c) NAD and NADP take part in many enzyme reactions involving dehydrogenases. Some of these include oxidation of alcohol to aldehyde, of glucose to gluconic acid, of malic acid to oxaloacetic acid, of lactic acid to pyruvic acid, of glycerophosphate to phosphoglyceraldehyde, of glucoses-phosphate to 6-phosphogluconate, of pyruvic acid to acetyl-CoA and of α- ketoglutarate to succinyl-CoA etc.
(d) The reduced NADP(NADPH) is also involved in enzyme reaction in fatty acid synthesis, synthesis of cholesterol and of steroid hormones and also in the formation of tetrahydrofolate (H4 folate).
The deficiency of niacin causes the disease pellagra. The clinical features of the disease include three D’S-dermatitis (lesion of skin of face, neck, knees, breasts, thick and scaly skin), diarrhoea, dementia (headache, depression, anxiety, insomnia and forgetfulness).
(a) In the deficiency of niacin, nicotinamide is given in a dose of 100 mg every 6 hours by mouth. The vitamin is well-absorbed but can be given parenterally. The response is very quick. The erythema of the skin diminishes and the diarrhoea ceases within 24 hours. Improvement is also found in the patient’s behaviour and mental attitude.
(b) The deficient disease is developed due to a low intake of protein including tryptophan. Deficiencies of other B vitamins (riboflavin and vitamin B6) are likely. Nicotinamide treatment should, therefore, be supplemented with a nutritious diet, high in protein.
(c) Vitamin B complex tablets should be given and iron, folic acid and vitamin B12 may be necessary in addition in some cases.
(d) Alcohol should be forbidden.
Pellagra can be prevented by enrichment of maize meal and bread with niacin.
In large doses, nicotinic acid, causes burning sensation that may ultimately alarm the patient.
Intake of niacin in excess of 500 mg/d can cause liver damage.
Water Soluble Vitamins: Type # 5. Pyridoxine (Vitamin B6):
a. In 1938, pyridoxine was isolated in a pure form by five different groups of workers.
b. In 1939, the vitamin was synthesized independently by two groups of workers in Germany and U.S.A., respectively.
a. Since pyridoxine occurs in nature it is a mixture of three compounds (pyridoxine, pyridoxal and pyridoxamine).
The structure of these three are given (Fig. 15.17):
The more active derivatives are pyridoxal and pyridoxamine phosphates. Pyridoxine is 3-hydroxy-4, 5-di-hydroxymethyl-2-methyl pyridine. Pyridoxal contains an aldehyde instead of hydroxyl methyl in No. 4 and pyridoxamine contains a primary amine side chain in No.4 of pyridine nucleus. These three compounds are interchangeable.
b. Pyridoxine is readily soluble in water.
c. When it is in alkaline solution, it is slowly destroyed by exposure to light.
d. It reacts with phenol reagent or 2:6 di-chloroquinone chlorimide producing coloured compounds.
Absorption and Storage:
It is readily absorbed from the small intestine. The excess amount, if ingested, is not stored in the body but is excreted in urine.
a. Pyridoxine is essential for the growth of infants.
b. Muscle phosphorylase contains 70-80% of total body vitamin B6.
(a) Pyridoxal phosphate, the active derivative of pyridoxine, functions as codecarboxylase in the decarboxylation of tyrosin, arginine, glutamic acid and certain other amino acids.
(b) The deaminases (dehydrases) for serine and threonine are also catalyzed by pyridoxal phosphate acting as coenzyme.
(c) Pyridoxal phosphate acts as cotransaminase in the transamination reactions.
(d) Pyridoxal phosphate acts as a coenzyme for kynureninase in the synthesis of niacin from tryptophan.
(e) Muscle phosphorylase also contains pyridoxal phosphate as coenzyme.
(f) Pyridoxal phosphate acts as coenzyme in the transulfuration reaction in the transfer of sulphur from methionine to serine to form cysteine.
(g) Pyridoxal phosphate is also involved in the process of absorption of amino acids from the intestine.
(h) Pyridoxal phosphate is also involved in the desulphuration of cysteine and homocysteine.
(i) Pyridoxal phosphate is required for the synthesis of α-aminolevulinic acid which is an important intermediate in the synthesis of porphyrin and heme nuclei.
(j) This pyridoxal phosphate especially applies to brain metabolism because it is necessary for the formation of serotonin, γ-aminobutyric acid and the catecholamines.
(k) Pyridoxal phosphate has also important relationship to oxalate metabolism. Hyperoxaluria occurs in deficiency states.
(1) Pyridoxal phosphate is involved in the synthesis of coenzyme A from pantothenic acid.
(m) Pyridoxal phosphate is concerned with immune response.
Fortunately, deficiency of vitamin B6 is rare because of its easy availability in most foodstuffs:
a. Deficiency gives rise to irritability and depression. In some subjects there are lymphopenia and peripheral neuropathy.
b. Deficiency of this vitamin occurs in infants on inadequate milk formulas. The major symptoms are convulsions due to depletion of brain Ƴ-amino-butyric acid content.
c. The drugs isonicotinic acid hydrazide and hydralazine act as B6 antagonist causing deficiency symptoms including hypochromic anemia and peripheral neuropathy.
d. In the deficiency states, there are inborn errors of metabolism including cystathioninuria, familial xanthurenic aciduria and some pyridoxal-responsive anemias.
e. The deficiency of this vitamin is found in nursing infants whose mothers are deficient of the vitamin due to long term use of oral contraceptives.
f. Alcoholics may also be deficient due to metabolism of ethanol to acetaldehyde which stimulates hydrolysis of the phosphate of the coenzyme.
g. Isoniazid, the antituberculosis drug, can produce vitamin B6 deficiency by forming a hydrazone with pyridoxal.
Vitamin B6 deficiency can occur in women taking oral contraceptives and the mild depression as a result of this may be relieved by a small dose of pyridoxine.
Doses of vitamin B6 (200 mg per day or more) taken for some weeks cause a sensory polyneuropathy.
Water Soluble Vitamins: Type # 6. Pantothenic Acid (Vit. B5):
a. In 1938, Williams and co-workers isolated this vitamin in a pure form as its calcium salt.
b. In 1940, its synthesis was accomplished by several groups of workers.
a. Pantothenic acid consists of β-alanine and pantoic acid joined through a peptide bond.
The chemical structure is given below (Fig. 15.18):
b. It is highly soluble in water.
c. It is stable to autoclaving at 120°C for 30 minutes in neutral solution but is destroyed in acid or alkaline medium.
d. It is not obtained in crystalline form but its sodium, potassium or calcium salts crystallise readily.
e. Pantothenic acid exists in the tissues in the active form as coenzyme A which contains pantothenic acid, β-mercaptoethylamine, adenine, ribose and phosphoric acid.
Absorption and Storage:
Pantothenic acid and its salts are readily absorbed from the small intestine through the portal vein into the general circulation.
If ingested in excess of the requirements, it is not stored in the body, but is excreted in urine or metabolised by the tissues.
Pantothenic acid is essential for the growth of infants and children.
(a) Pantothenic acid as a constituent of coenzyme A is required for several fundamental reactions in metabolism.
(b) Coenzyme A combines with acetate to form “active acetate” (acetylcoenzyme A) which is directly utilized by combination with oxaloacetic acid to form citric acid which initiates the citric acid cycle.
(c) Acetyl-CoA derived from carbohydrates, fats or many of the amino acids undergoes further metabolism through the “common metabolic pathway”.
(d) In the form of active acetate, acetic acid also combines with choline to form acetylcholine or with the sulfonamide drugs which are acetylated prior to excretion.
(e) The decarboxylated product of α-ketoglutarate in the citric acid cycle is a coenzyme A derivative called “active succinate” (succinyl-CoA). Succinyl-CoA and glycine are involved in the first step leading to the biosynthesis of heme. So anemia occurs in deficiency of this vitamin.
(f) In lipid metabolism, coenzyme A has got significant role. In the first step of oxidation of fatty acids, the fatty acids are to be activated by coenzyme A catalysed by the enzyme thiokinase. In each turn of the β- oxidation cycle, one molecule of acetyl- CoA is released. This acetyl-CoA directly enters the citric acid cycle for degradation to carbon dioxide and water or two molecules of acetyl-CoA condense to form ketone bodies.
(g) Coenzyme A in the form of acetyl-CoA is also required for the synthesis of cholesterol and thus of the steroid hormones.
(h) A significant amount of the cellular pantothenic acid is protein-bound. This form is contained in a compound known as acyl carrier protein, a coenzyme required in the biosynthesis of fatty acids.
(i) Coenzyme A is also involved in the metabolism of propionate and of branch chain fatty acids.
Deficiency of this vitamin in humans results in nausea, vomiting, certain gastrointestinal disorders, irritability, inadequate growth, anemia, fatty liver, failure in gaining weights.
Pantothenate deficiency causes burning foot syndrome in prisoners of war and is associated with reduced capacity for acetylation.
No ill-effects are still reported.