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DSM in Animal Nutrition & Health

Pantothenic Acid

Properties and Metabolism

Pantothenic acid is found in two enzymes, coenzyme A (CoA) and acyl carrier protein (ACP), which are involved in many reactions in carbohydrate, fat and protein metabolism. The structural formula and crystalline structure are shown in Illus. 14-1. The free acid of the vitamin is a viscous, pale yellow oil readily soluble in water and ethyl acetate. It crystallizes as white needles from ethanol and is reasonably stable to light and air. The oil is extremely hygroscopic and easily destroyed by acids, bases and heat. Maximum heat stability occurs at pH 5.5 to 7.0. Calcium pantothenate is the pure form of the vitamin used in commerce. Pantothenic acid is optically active (characteristic of rotating a polarized light). It may be prepared either as the pure dextrorotatory (d) form or the racemic mixture (dl) form. The racemic form has approximately one-half the biological activity of d-calcium pantothenate. Only the dextrorotatory form, d-pantothenic acid, is effective as a vitamin. The most common antagonist of pantothenic acid is omega-methyl-pantothenic acid, which has been used to produce a deficiency of the vitamin in humans (Hodges et al., 1958). Other antivitamins include pantoyltaurine; phenylpantothenate hydroxycobalamine (c-lactam), an analog of vitamin B12; and antimetabolites of the vitamin containing alkyl or aryl ureido and carbamate components in the amide part of the molecule (Fox, 1991; Brass, 1993).

 

Illustration 14-1

14Illustration_14-1_PanthothenicAcid

Pantothenic acid is found in feeds in both bound (largely as CoA) and free forms. It is necessary to liberate the pantothenic acid from the bound forms in the digestive process prior to absorption. Work with chicks and rats indicated that pantothenic acid, its salt, and the alcohol are absorbed primarily in the jejunum by a specific transport system that is saturable and sodium ion dependent (Fenstermacher and Rose, 1986; Miller et al., 2006). The alcohol form, panthenol, which is oxidized to pantothenic acid in vivo, appears to be absorbed somewhat faster than the acid form. After absorption, pantothenic acid is transported to various tissues in the plasma from which it is taken up by most cells via another active-transport process involving cotransport of pantothenate and sodium in a 1:1 ratio (Olson, 1990). Within tissues, pantothenic acid is converted to CoA and other compounds where the vitamin is a functional group (Sauberlich, 1985). Free pantothenate appears to be efficiently absorbed; in the dog between 81% and 94% of an oral dose of sodium [14C] pantothenate was absorbed (Taylor et al., 1974). Measurement of pantothenic acid bioavailability in adult men consuming a typical United States diet ranged from 40% to 61%, with an average of 50% (Sauberlich, 1985). Urinary excretion is the major route of body loss of absorbed pantothenic acid, and excretion is prompt when the vitamin is consumed in excess. Most pantothenic acid is excreted as the free vitamin, but some species (e.g., dog) excrete it as beta-glucuronide (Taylor et al., 1972). An appreciable quantity of pantothenic acid (~15% of daily intake) is oxidized completely and is excreted across the lungs as CO2.Livestock do not appear to have the ability to store appreciable amounts of pantothenic acid; organs such as the liver and kidneys have the highest concentrations. The majority of pantothenic acid in blood exists in red blood cells as CoA, but free pantothenic acid is also present.

 

Functions

Pantothenic acid is a constituent of two important coenzymes, CoA and ACP. Coenzyme A is found in all tissues and is one of the most important coenzymes for tissue metabolism. The coenzymes are known to be involved in more than 100 different metabolic pathways involving the metabolism of carbohydrates, proteins and lipids and the synthesis of lipids, neurotransmitters, steroid hormones, porphyrins and hemoglobin. The important role of CoA is summarized in Figure 14-1.

 

Figure 14-1: The Important Role of Coenzyme A (CoA) in Metabolism

14Figure_14-1_The_Important_Role_of_Coenzyme_A

The most important function of CoA is to act as a carrier mechanism for carboxylic acids (Lehninger, 1982; Miller et al., 2006; Rucker and Bauerly, 2007). Such acids, when bound to CoA, have a high potential for transfer to other groups, and such carboxylic acids are normally referred to as “active.” The most important of these reactions is the combination of CoA with acetate to form “active acetate” with a high-energy bond that renders acetate capable of further chemical interactions. The combination of CoA with two-carbon fragments from fats, carbohydrates and certain amino acids to form acetyl-CoA is an essential step in their complete metabolism because the coenzyme enables these fragments to enter the TCA cycle. For example, acetyl-CoA is utilized directly by combining with oxaloacetic acid to form citric acid, which enters the tricarboxylic acid (TCA) cycle. Coenzyme A, along with ACP, functions as a carrier of acyl groups in enzymatic reactions involved in synthesis of fatty acids, cholesterol and other sterols; oxidation of fatty acids, pyruvate and alpha-ketoglutarate; and biological acetylations. In the form of acetyl-CoA, acetic acid can also combine with choline to form acetylcholine, a chemical transmitter at the nerve synapse, and can be used for detoxification of various drugs, such as sulfonamides. Decarboxylation of alpha-ketoglutaric acid in the TCA cycle yields succinic acid, which is then converted to the “active” form by linkage with CoA. Active succinate and glycine are together involved in the first step of heme biosynthesis. Pantothenic acid also stimulates synthesis of antibodies, which increase resistance of animals to pathogens. It appears that when pantothenic acid is deficient, the incorporation of amino acids into the blood albumin fraction is inhibited, which would explain why there is a reduction in the titer of antibodies (Axelrod, 1971).

 

Requirements

The pantothenic acid requirements for poultry vary among species and classes from approximately 2 to 16 mg per kg (0.9 to 7.3 mg per lb) of diet (NRC, 1994). For growth and reproduction, the majority of species have a dietary requirement between 9 and 16 mg per kg (4.1 and 6.8 mg per lb). For chicken egg production, the pantothenic acid requirement is very low (2 mg per kg; 0.9 mg per lb) compared with a requirement of 10 mg per kg (4.5 mg per lb) for growth and reproduction respectively. Hatchability was not increased in turkey eggs from hens fed supplemental pantothenic acid or with egg pantothenic acid injections, which suggests that pantothenic acid is not limiting for hatchability in commercial turkey hen diets that contain 10.5 mg per kg (4.77 mg per lb) or more pantothenic acid (Robel, 1993a). Requirements are based on typical consumption levels. When energy density of diets is increased, intake is reduced, so that higher dietary concentrations of pantothenic acid and other vitamins are required. When the level of energy in the rations of broilers was raised from 2,870 to 3,505 kcal per kg (1,300 to 1,590 kcal per lb), intake of pantothenic acid fell by 19.1% because appetite is mainly controlled by an intake of energy (Friesecke, 1975). It has been suggested that antibiotics may have a sparing effect on the pantothenic acid requirement of animals. A dietary level of 22 mg per kg (10 mg per lb) aureomycin for weanling pigs (McKigney et al., 1957) and 10 mg per kg (4.5 mg per lb) procaine penicillin for turkey poults (Slinger and Pepper, 1954) reduced the pantothenic acid requirement for these species. Certain amounts of B-complex (including pantothenic acid) vitamins are synthesized in the large intestine of poultry and other monogastric animals. It is doubtful, however, whether much benefit is derived, as only limited pantothenic acid absorption occurs in the large intestine, with greatest benefit being in animals that practice coprophagy (Friesecke, 1975).

Interrelationships with other vitamins on pantothenic acid requirements are known, for example those between pantothenic acid and vitamin B12 and between ascorbic acid and biotin (Scott et al., 1982). The pantothenic acid requirement of chicks from B12-depleted hens was found to be greater than that of chicks from normal hens. A five-fold increase in coenzyme A content of liver was found in B12-deficient chicks and rats. Also, there have been suggestions of a possible interrelationship between folic acid and biotin with pantothenic acid. Both vitamins were found necessary for pantothenic acid utilization in the rat (Wright and Welch, 1943). The inclusion of biotin in the diet of a pantothenic acid-deficient pig was effective in prolonging the life of the pig, but allowed the pantothenic acid deficiency signs to appear in half the time (Colby et al., 1948). 

 

Sources

Pantothenic acid is widely distributed in feedstuffs of animal and plant origin. Alfalfa hay, peanut meal, cane molasses, yeast, rice bran, green leafy plants, wheat bran, brewer’s yeast, fish solubles and rice polishings are good sources of the vitamin for animals. Corn and soybean meal diets are apt to be low in pantothenic acid. Milling by-products, such a rice bran and wheat bran, are good sources, being two to three times higher than the respective grains.

Many poultry diets are borderline in supplying pantothenic acid requirements and many are deficient in this vitamin Biological availability of pantothenic acid is high from corn and soybean meal, but low from barley, wheat and sorghum (Southern and Baker, 1981). Changing processing methods can greatly alter vitamin feed levels. As an example, with changes in sugar technology, literature values for pantothenic acid content of beet molasses have decreased from 50 to 100 mg per kg (22.7 to 45.5 mg per lb) in the 1950s to about 1 to 4 mg per kg (0.45 to 1.8 mg per lb) more recently (Palagina et al., 1990).

Pantothenic acid is reported to be fairly stable in feedstuffs during long periods of storage (Scott et al., 1982). The authors indicate that heating during processing may cause considerable losses, especially if temperatures attain 100° to 150°C for long periods of time and pH values are above 7 or below 5. Gadient (1986) considers pantothenic acid to be slightly sensitive to heat, oxygen, or light, but very sensitive to moisture. Pelleting was reported to cause only small losses of the vitamin. As a general guideline, pantothenic acid activity in normal pelleted feed over a period of three months at room temperature should be 80% to 100%. Pantothenic acid loss during processing of human foods is significant and can amount to as much as 70% in frozen meat and 80% in canned legumes. Loss of the vitamin in dairy products during processing and storage is about 30% to 35% (Song, 1990).

Higher concentrations of pantothenic acid are found in the rumen than are found in the dietary components, indicating microbial synthesis of the vitamin. Pearson et al., (1953) found that the urinary and fecal excretion of pantothenic acid was four to six times the intake when semi-synthetic diets were fed. Pantothenic acid excretion increased with increased crude protein intakes. For young ruminants, milk from the dam is a good source of the vitamin, with colostrum and whole milk from cows containing about 1.73 and 3.82 µg of pantothenic acid per ml, respectively (Foley and Otterby, 1978).

Pantothenic acid is available as a commercially synthesized product for addition to feed. It is available as d- or dl-calcium pantothenate. One gram of d-calcium pantothenate is equivalent to 0.92 grams of pantothenic acid activity, while the racemic mixture of 1 gram of the dl form has 0.46 gram of d-pantothenic acid activity. Because livestock and poulty can utilize, biologically, only the d isomer of pantothenic acid, nutrient requirements of the vitamin are routinely expressed as the d form.

 

Deficiency

The major lesions of pantothenic acid deficiency for poultry appear to involve the nervous system, adrenal cortex and skin (Scott et al., 1982). Pantothenic acid deficiency reduces normal egg production and hatchability. Embryos from panthothenic acid deficient hens have been observed to have subcutanous hemorrhages and severe edema, with most of the mortality showing up during the later part of the incubation period (Leeson and Summers, 2001). In chickens, a decline of growth is followed by decline in feed conversion and retardation of feather growth. Plumage becomes rough and ruffled, and feathers become brittle and may fall; next dermatitis rapidly develops in chicks. Corners of the beak and the area below the beak are most affected, but the disorder is also observed in feet. Outer layers of skin between toes and on bottoms of feet peel off, and small cracks and fissures appear. In some cases, skin layers of feet thicken and cornify, and wart-like protuberances develop on balls of the feet. The foot problem is usually exacerbated by bacterial invasion of the lesions. Within 12 to 14 days after chickens begin a deficient diet, the margins of the eyelids are sealed closed by a viscous discharge. Illus. 14-2 illustrates the typical deficiency syndrome in the chick.

 

Illustration 14-2: Pantothenic Acid Deficiency

14Illustration_14-2_Pantothenic_Acid_Deficiency

Pantothenic acid concentrations in the liver are reduced during deficiency. Liver is hypertrophied, and it varies in color from faint yellow to dirty yellow. Nerves and fibers of the spinal cord show myelin degeneration. These degenerating fibers occur in all segments of the cord down to the lumbar region (Scott et al., 1982). In young chicks, deficiency signs of pantothenic acid deficiency are difficult to differentiate from biotin deficiency since both cause severe dermatitis, broken feathers, perosis, poor growth and mortality. In pantothenic acid deficiency, dermatitis of the feet is evident over the toes, in contrast to biotin deficiency, which primarily affects the foot pads and is often more severe than a deficiency of pantothenic acid (McDowell, 2000). Signs of pantothenic acid deficiency in young turkeys, which are similar to those in young chickens, include general weakness, dermatitis and sticking together of eyelids (Illus. 14-3). Young ducks do not show the signs usually seen in chickens and turkeys except for retarded growth; however, their mortality rate is very high. Poor feathering is the most prevalent deficiency sign in pheasants and quail (Scott et al., 1964).

 

Illustration 14-3: Pantothenic Acid Deficiency

14Illustration_14-3_Pantothenic_Acid_Deficiency

A pantothenic acid deficiency does not normally affect egg production but severely depresses hatchability, and chicks that hatch may be too weak to survive. Embryonic mortality in pantothenic acid deficiency occurs usually during the last few days of incubation. A direct linear relationship exists between dietary pantothenic acid and hatchability. Beer et al. (1963) fed White Leghorn hens a purified diet that contained 0.9 mg of pantothenic acid per kg (0.4 mg per lb) of diet. They found that the hens required addition of 1 mg of pantothenic acid per kg (0.45 mg per lb) of diet for optimum egg production, at least 4 mg per kg (1.8 mg per lb) of diet for maximum hatchability and 8 mg per kg (3.6 mg per lb) of diet for optimum hatchability and viability of offspring. Dawson et al. (1962) reported that turkey breeder hens fed a diet deficient in pantothenic acid demonstrated high embryonic mortality during the first week of development. After 17 days, the surviving embryos were small and poorly feathered, and they showed signs of edema, hemorrhaging, fatty livers and pale, dilated hearts.

 

Fortification Considerations

Poultry diets based on grains, particularly corn, are routinely supplemented with pantothenic acid. For a practical corn-soybean meal diet, there was no effect of pantothenic acid supplementation for White Leghorn pullets 0 to 6 weeks of age (Bootwalla and Harms, 1991), for broilers aged 0 to 21 days (Harms and Nelson, 1992) or turkeys aged 0 to 4 weeks (Harms and Bootwalla, 1992b). However, although turkeys grew normally to 21 days without signs of pantothenic acid deficiency, increasing intake of pantothenic acid improved feed efficiency (Ruiz and Harms, 1989). Scott et al.(1982) concluded that practical diets usually contain sufficient pantothenic acid for all classes of chickens, but a number of factors may influence the requirement for this vitamin. Increasing supplemental pantothenic acid to turkey breeding hens increased the transfer of pantothenic acid in eggs (Robel, 1993a). Scott (1966) indicated that the pantothenic acid requirement for poultry might have to be increased 60% to 80% due to a lack of availability from bound forms in feeds. Southern and Baker (1981) estimated that pantothenic acid in both corn and dehulled soybean meal was 100% bioavailable. The bioavailability of pantothenic acid in barley, wheat and sorghum, however, was estimated to be only 60% based on chick growth bioassay. Nevertheless, corn and sorghum contained less bioavailable total pantothenic acid than barley and wheat because of less total content of the vitamin. Clinical pantothenic acid deficiency signs appear to be completely reversible, if not too far advanced, by oral treatment or injection with the vitamin followed by restoration of an adequate level of pantothenic acid in the diet. Type of diet influences need for pantothenic acid supplementation. High-protein diets reduce pantothenic acid needs due to the decreased level of dietary carbohydrate, which presumably would require coenzyme A for metabolism. Pigs fed a pantothenic acid-deficient high-fat diet failed to gain weight, exhibited a lower feed efficiency ratio and developed deficiency signs more quickly than pigs fed diets low in fat (Sewell et al., 1962). Biotin and folic acid have been found necessary for pantothenic acid utilization, and vitamin B12 and antibiotics have a sparing effect for chicks (Latymer and Coates, 1981) and pigs (Latymer et al., 1985). Pantothenic acid is available as a commercially synthesized product for addition to feed. It is available as d- or dl-calcium pantothenate. One gram of d-calcium pantothenate is equivalent to 0.92 gm of d-pantothenic acid activity. A racemic mixture (equal parts d- and dl-calcium pantothenate) is generally sold to the feed industry. Because livestock and poultry can biologically utilize only the d-isomer of pantothenic acid, nutrient requirements for the vitamin are routinely expressed in the d-form.

Feed-grade pantothenic acid products are available in a number of potencies. Products that are sold on the basis of racemic mixture content can be misleading and confusing to a buyer who is not fully aware of the biologic activity supplied by d-calcium pantothenate. To avoid confusion, the label should clearly state the grams of d-calcium pantothenate or its equivalent per unit weight and the grams of d-pantothenic acid.

A straight racemic mixture is available to the feed industry, but its hygroscopic and electrostatic properties contribute to handling problems. Readily picking up moisture, it sticks to packing materials and feed manufacturing and processing equipment, and it can become hard after long exposure to air. Its electrostatic properties cause it to cling to metallic and other objects, and losses can be significant. Through complexing procedures, several companies now market free-flowing, essentially non-hygroscopic and non-electrostatic products.

Verbeeck (1975) reported calcium pantothenate to be stable in premixes with or without trace minerals, regardless of the mineral form. Losses of calcium pantothenate may occur in premixes that are extremely acidic in nature. Use of a calcium pantothenate-calcium chloride complex instead of the plain calcium pantothenate should alleviate this problem.

There is controversy on the concept of removing vitamins and trace mineral supplementation from poultry and other species’ diets sometime prior to slaughter. Skinner et al. (1992) reported that removal of vitamins and trace minerals from broiler diets did not affect performance. However, Teeter and Deyhim (1993) detected reduced performance and carcass variables when the same period was examined. Increased dietary fortification with pantothenic acid elevated (P < 0.05) pectoralis muscle concentration of the vitamin (Deyhim et al., 1992b). Such effects of removing vitamin supplementation have the potential to affect consumer perception of poultry meat as wholesome and should be considered when vitamin withdrawal is being contemplated.

 

Vitamin Safety

Pantothenic acid is generally regarded as nontoxic. It is clear that dietary levels of at least 20 gm pantothenic acid per kg (9.0 gm per lb) can be tolerated by most species (NRC, 1987). Pantothenic acid can become toxic at around 2,000 mg per kg (909 mg per lb), where reduced growth rate associated with liver damage is seen (Leeson and Summer, 2001).