DSM in Animal Nutrition & Health
Properties and Metabolism
Pantothenic acid is found in two enzymes, coenzyme A (CoA) and acyl carrier protein (ACP). These enzymes 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).
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). 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). Coenzyme A is synthesized by cells from pantothenic acid, ATP, and cysteine. Pantothenic acid kinase, a cytosolic enzyme, is rate limiting for the overall pathway of coenzyme A biosynthesis (Brass, 1993). 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.
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. The vitamin also participates in the synthesis of heme, cholesterol, and acetylcholine.
Figure 14-1: The Important Role of Coenzyme A (CoA) in Metabolism
The most important function of CoA is to act as a carrier mechanism for carboxylic acids (Miller et al., 2006; Rucker and Baverly, 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).
For growth and reproduction, the majority of animal species have a dietary requirement between 5 and 15 mg per kg (2.3 to 6.8 mg per lb) of diet. However, requirements for ruminants are unknown. Normally the rumen microflora synthesize adequate pantothenic acid to prevent outright deficiency symptoms; however, biosynthesis depends on the composition of feed. Vitamin synthesis is reduced with diets high in cellulose but increases with higher quantities of soluble carbohydrates (Virtanen, 1966). Rumen microbial synthesis of pantothenic acid in the bovine appears to be 20 to 30 times more than dietary amounts (NRC, 2001). Sheep fed an artificial diet devoid of pantothenic acid for 3 weeks had 29 mg of pantothenic acid entering the duodenum (Finlayson and Seeley, 1983). The amount of pantothenic acid entering the duodenum ranged from the same as the amount provided by the diet to over four times more than the dietary supply in sheep fed typical diets (Finlayson and Seeley, 1983). Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg per kg (1 mg per lb) of digestible organic matter consumed per day and degradation of dietary pantothenic acid in the rumen is estimated to be 78% (Zinn et al., 1987).
Certain amounts of B-vitamins, including pantothenic acid, are synthesized in the large intestine of monogastrics as well as ruminant species. It is doubtful, however, whether much benefit is derived, as only limited pantothenic acid absorption occurs in the large intestine (Friesecke, 1975).
The pantothenic acid requirement of the young calf or any other pre-ruminant animal is unknown, but no clinical signs of pantothenic acid deficiency were observed in calves fed liquid diets providing 13 mg per kg (5.9 mg per lb) of diet (NRC, 1989).
Pantothenic acid is widely distributed in feedstuffs of animal and plant origin, hence its name is derived from “pantothenic,” meaning from all sides, or ubiquitous. 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 byproducts such as rice bran and wheat bran are good sources, being two- to three times-higher than their respective grains.
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) reported that the urinary and fecal excretion of pantothenic acid exceeded intake by four to six times when semi-synthetic diets were fed. Pantothenic acid excretion increased with increased crude protein intake. 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 d- or dl-calcium pantothenate for commercial use. One gram of d-calcium pantothenate is equivalent to 0.92 g of pantothenic acid activity. Because livestock and poultry can utilize only the d-isomer of pantothenic acid, nutrient requirements of the vitamin are routinely expressed on the basis of d-pantothenate.
Pantothenic acid is not normally required in the diet of adult ruminants, because ruminal microorganisms synthesize this vitamin in adequate amounts. Pantothenic acid deficiency has been produced experimentally in calves (Johnson et al., 1947; Sheppard and Johnson, 1957; Roy, 1980). Major clinical signs include anorexia, reduced growth, weakness of legs, rough hair coat, dermatitis, diarrhea and eventual death. The most characteristic pantothenic acid deficiency sign in the calf is scaly dermatitis around the eyes (spectacle eye) and muzzle. Anorexia and diarrhea follow after 11 to 20 weeks on a deficient diet. Calves become weak and unable to stand and may develop convulsions. They are susceptible to mucosal infection, especially in the respiratory tract. Postmortem studies have shown moderate sciatic and peripheral nerve demyelination. There is some edema in muscular tissue. When deficient calves received calcium pantothenate, they responded with increased appetite and weight gains and subsequent reversal of dermatitis and other symptoms.
Pantothenic acid deficiency in animals with functioning rumens is unlikely because the vitamin is produced by ruminal microbial synthesis. Supplementation of pantothenic acid at five to ten times the theoretical requirements did not improve performance of feedlot cattle (Cole et al., 1982; Zinn et al., 1987). Supplementation would be required for pre-ruminants receiving milk replacers. Recommended pantothenic acid supplementation for calves receiving milk replacer is 13 mg per kg (5.9 mg per lb) of dry matter (NRC, 1989). In calves with pantothenic acid deficiency, intramuscular injections of 0.5 g of pantothenic acid the first day, followed by 0.1 g daily thereafter, corrected the deficiency in cases that were not too far advanced (Sheppard and Johnson, 1957). Pantothenic acid is reportedly 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 reach 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, very sensitive to moisture and not very sensitive to oxygen or light. Pelleting was reported to cause only small losses of the vitamin. As a general guideline, pantothenic acid activity in pelleted feed stored for three months at room temperature should be 80% to 100% of the original value. Pantothenic acid stability in a vitamin premix was 98% after six months; however, when the premix contained choline and trace minerals, the residual activity of the vitamin was only 58% (Coelho, 1991).
Pantothenic acid is generally regarded as nontoxic. No data have been reported for pantothenic acid toxicity studies with ruminants. Dietary levels of at least 20 gm of pantothenic acid per kg (9.0 gm per lb) can be tolerated by most species (NRC, 1987). Pantothenic acid in poultry 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)