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Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA
2To whom correspondence should be addressed. E-mail: jgmorris{at}ucdavis.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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16 g/kg Phe + Tyr. Cats fed diets with <16 g Phe + Tyr developed "red hair." We confirmed the anecdotal reports that the black hair of cats can change from black to reddish brown. An aromatic amino acid concentration 
18 g/kg is recommended for the prevention of visually discernible red hair in black-coated cats. Dietary concentrations >18 g total aromatic amino acids/kg diet promote a greater ratio of PTCA:total melanin in hair. We are unaware of a secondary nutrient requirement being so much greater than the requirement for growth.
KEY WORDS: • melanin • eumelanin • tyrosine • phenylalanine • cats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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). Two types of melanin are synthesized in follicular melanocytes: eumelanin, which is brown to black, and pheomelanin, which is reddish-brown (2
). The pathways for the synthesis of these two types of melanin were presented by Morris et al. (3
). The physiologic signals that regulate this switch include the 
-melanocyte–stimulating hormone and the agouti protein (4
). Dihydroxyphenylalanine (DOPA),3
the hydroxylated product of tyrosine, is the precursor of both types of melanin. We have been unable to find any reference to the effect of dietary tyrosine (or phenylalanine) on the color of mammalian hair. However, the tendency for phenylketonuric human subjects to have fair hair has been commented upon from time to time since the first observations of Folling in 1934 (5
).
Rogers and Morris (6
) demonstrated that phenylalanine was an essential amino acid for growing kittens, but tyrosine was dispensable when the diet contained adequate Phe. These authors also demonstrated that the phenylalanine requirement for maximal growth was not >7.5 g/kg diet in the presence of 10 g tyrosine/kg diet. Anderson et al. (7
), using Latin-square designs, showed that the phenylalanine requirement of growing kittens was not >5 g/kg diet in the presence of 5 g tyrosine/kg diet. Further refinements to the aromatic amino acid requirement of growing kittens were made by Williams et al. (8
) who reported a total requirement of 7.5 g/kg diet, of which about half could be supplied by tyrosine. This latter study used a Latin-square design of 10-d periods and based the requirement on the minimal phenylalanine or phenylalanine plus tyrosine for maximal growth and nitrogen balance. The NRC (9
) recommended a total aromatic amino acid requirement of 8.5 g/kg diet, with a minimum of 4.0 g phenylalanine/kg diet. The above values plus a slight overage for bioavailability were used by the Association of American Feed Control Officials (AAFCO) (10
) for the Cat Food Nutrition Profile used by the pet food industry. AAFCO (10
) recommended that diets for both kittens and adult cats should contain 8.8 g phenylalanine plus tyrosine/kg diet with a minimum of 4 g phenylalanine.
Subsequent longer-term studies (11
) demonstrated that diets based on gelatin, containing amino acids in excess of the NRC (9
) recommendations, resulted in the coat hair of black cats turning reddish-brown. The change in coat color was also produced when cats consumed diets based on isolated amino acids that included 12 g phenylalanine plus 4.5 g tyrosine/kg diet. These levels were greatly in excess of those recommended (9
,10
). However, when black cats consumed a diet that contained 24 g phenylalanine/kg diet, and no tyrosine, there was no change in hair color. These studies indicated that the recommended (9
,10
) levels of phenylalanine and tyrosine were inadequate to maintain black hair coat in cats.
The present study investigated the effects of a range of dietary levels of phenylalanine and tyrosine on coat color in black cats. Studies were conducted over periods of 6–9 mo to assess the level of dietary phenylalanine and tyrosine required to maintain black hair color.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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Specific pathogen–free domestic short-hair cats and kittens (n = 53) with black hair coats from the Feline Nutrition and Pet Care Center, University of California at Davis were used. At all times, cats and kittens consumed a purified diet and water ad libitum. The experimental protocol was approved by the Animal Use and Care Administrative Advisory Committee University of California, Davis and conducted in accordance with the NIH guidelines (12
) and the Animal Welfare Act. Cats were housed either singly in 60 x 60 x 60 cm stainless steel metabolic cages or in pairs in 1.4 m2 cages. Room temperature was maintained at 21 ± 2°C with a minimum light:dark cycle of 14 h/10 h.
Diets.
Eleven purified diets containing the following proportions of phenylalanine and tyrosine, respectively (g/kg diet) were prepared: 4 + 2; 4 + 4; 4 + 6; 4 + 8; 10 + 0; 10 + 2; 10 + 4; 10 + 6; 10 + 8; 10 + 10; 24 + 0. Crystalline amino acids (Ajinomoto USA, Teaneck, NJ) supplied the nitrogen in all diets, and the essential amino acids with the exception of phenylalanine and tyrosine, were supplied at 1.6–2 times the NRC (9
) recommendations. The crude protein (N x 6.25) was held constant at 280 g/kg diet by using an essential (EAA) and a dispensable (DAA) amino acid mixture. The amount of the DAA mixture was adjusted for the nitrogen supplied as phenylalanine and tyrosine. The EAA mixture contained (g/kg diet): L-Arg · HCl, 20; L-His · HCl · H2O, 6; L-Ile, 10; L-Leu, 24; L-Lys · HCl, 16; L-Met, 8; L-Cys, 7; L-Thr, 14; L-Trp, 3; L-Val, 12. The DAA mixture contained (g/kg): L-Ala, 175; Gly, 175; L-Gln, 175; L-Glu, 75; L-Asn, 150; L-Asp, 100; L-Pro, 150.
The constant ingredients in the diets were as follows (g/kg diet): chicken fat (Foster Farms, Livingston, CA) 240; starch (Melojel, National Food Starch and Chemical, Bridgewater, NJ) 275.5; sucrose, 100; cellulose, 20; mineral mixture 50 (8
); vitamin mixture 5 (8
); choline chloride (Du Pont, Highland, IL), 4.5; sodium acetate (Fisher Scientific, Santa Clara, CA) to balance the hydrochloride associated with arginine, histidine and lysine; taurine (Taisho Pharmaceutical, Torrance, CA) 2.5. The diets were blended in a 40-L food mixer, which produced a diet with a consistency similar to cookie dough, and were given to the cats in this form.
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Experimental design |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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). The ages of the cats in group 1 ranged from 3 to 8 mo, those in groups 2 and 3, 2–3 mo and cats in group 4, 2–4 mo The groups are described below.
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Cats in this group had initial body weights ranging from 2.1 to 4.1 kg; they were older than those in groups 2–4 and included 13 females and 5 males. Treatments commenced on March 6, 1999 and continued for 269 d. The cats were allocated as follows to the dietary treatments: Phe + Tyr 4 + 2 (2 females); 4 + 4 (2 females); 4 + 6 (2 females); 4 + 8 (1 male and 1 female); 10 + 0 (2 females); 10 + 2 (4 males); 10 + 4 (2 females) and 10 + 6 (2 females).
Group 2.
The 7 males and 4 females in this group had initial body weights that ranged from 0.9 to 1.7 kg. Treatments commenced on April 26, 1999 and continued for 227 d. The cats were allocated to the dietary treatments as follows: Phe + Tyr: 4 + 2 (1 male and 1 female); 4 + 4 (2 males); 4 + 6 (1 male); 4 + 8 (1 female); 10 + 0 (2 males); 10 + 2 (1 male and 1 female) and 10 + 6 (1 female).
Group 3.
The 5 males and 5 females in this group had initial body weights that ranged from 0.9 to 1.2 kg. Treatments commenced on August 20 1999 and continued for 210 d. The cats were allocated to the following dietary treatments Phe + Tyr: 4 + 2 (four males); 4 + 6 (2 males); 4 + 8 (2 males); 10 + 2 (2 males) and 10 + 4 (2 males).
Group 4.
The 5 females and 7 males in this group had initial body weights of 0.8 to 1.5 kg and were allocated to the three dietary treatments Phe + Tyr: 10 + 8 (2 males and 2 females); 10 + 10 (3 males and 1 female) and 24 + 0 (2 males and 2 females). Treatments commenced May 5, 2000 and continued for 191 d.
Food intakes were measured daily and body weights were recorded weekly. Blood samples (3 mL) were drawn from the jugular veins of unanesthetized cats into heparinized syringes every 1–2 mo. Plasma was frozen at -80°C until analyzed for free amino acids. At the beginning of each experiment, a rectangular area approximately 7 x 5 cm on the lateral abdomen of each cat was shaved. New hair growth within this area was evaluated for the presence of red hairs and then shaved at the time of each blood sampling and used for the analysis of melanin or pyrrole-2,3,5-tricarboxylic acid (PTCA).
Analytical methods.
Plasma amino acid concentrations were determined on a Model 7300 Beckman Amino Acid Analyzer (0.4 cm x 10 cm column packed with spherical cation exchange resin, Beckman Instruments, Palo Alto, CA). Before analysis, plasma was mixed with an equal volume of 0.28 mol/L sulfosalicylic acid. The resulting precipitate was removed by centrifugation at 16,000 g. Lithium hydroxide was added to an aliquot of the supernatant to adjust the pH to 2.2 and the equivalent of 20 µL of plasma was injected onto the column of the analyzer.
Total melanin was determined according to the method of Ozeki et al. (2
) by dissolving 5 mg hair in 3 mL of Soluene-350 (Packard Instrument, Meriden, CT). Once the hair was completely solubilized, the optical density was determined in a Beckman Recording Quartz Spectrophotometer (Beckman Instruments, Fullerton, CA) at wavelengths of 500 and 650 nm; the latter wavelength provides an index of the proportion of pheomelanin in the hair. A standard curve for total melanin was constructed using Sepia melanin standards (Sigma Chemical, St. Louis, MO) dissolved in Soluene-350. The CV of the total melanin assay was 5.6% for black cat hair. Analyses were done in triplicate.
The measurement of PTCA concentration in hair was based on a modification of the peroxide oxidation method of Ito and Wakamatsu (13
). Briefly, 10 mg hair was added to a mixture of 100 µL deionized water, 840 µL K2CO3 (1 mol/L) and 60 µL H2O2 (30%) in a 20 x 125 mm screw-cap Pyrex culture tube (Corning Glass Works, Corning, NY). The tubes and contents were placed in a 90°C water bath until the hair was digested. After the sample had cooled to room temperature, 20 µL Na2SO3 (10%) and 500 µL HCl (6 mol/L) were added to the digest. The samples were twice extracted with 7 mL diethyl ether, and extracts were pooled and evaporated under nitrogen. The residue was suspended in 200 µL deionized water and 20 µL was injected onto a 4.6 mm x 250 mm Xterra MS C18 5 µm HPLC column (Waters, Milford, MA) heated to 55°C with a phosphate buffered mobile phase at pH 2.1 containing 2% (v/v) methyl alcohol. A Rainin LDC (Emeryville, CA)/Milton Roy Spectro Monitor 3000 detector (Rochester, NY) at a wavelength of 269 nm was used. The retention time of the major peak area corresponded to that of the PTCA (5
) working standard, which was prepared according to the method of Ito and Wakamatsu (13
) and standardized by comparison with a sample kindly supplied by Dr. Ito. The CV for the working standard of PTCA was 1.1%, and for digested and ether-extracted hair from a control cat, was 3.5%.
In addition to the objective measurements of melanin and PTCA, the overall hair color of the cats was subjectively assessed by a visual scoring system using a scale of 0 to 6 in which 0 = black, 1 = slight brown tinge, 2 = brownish black, 3 = medium brown, 4 = light brown, 5 = gray-light brown, 6 = gray.
Statistical analyses.
Data were analyzed by one-way ANOVA and the post-hoc Tukey-Kramer multiple comparisons test. differences were considered significant at P < 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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. The decline in concentration of PTCA indicated that there was a decrease in eumelanin concentration in hair. In contrast, in Figure 2
, the mean PTCA concentrations in the hair of the cats from the 10 + 6 to the 24 + 0 g/kg dietary treatments followed a positive trend with time, indicating increasing concentrations of eumelanin in hair. In this figure, the values for the cats in the 10 + 8 g/kg group remained almost constant and the concentrations for the 10 + 6 g/kg treatments were negatively related with the time they received the diet. These observations indicate that a concentration of 10 + 6 g/kg Phe + Tyr is inadequate to maintain black hair. This was supported by the visual assessment of overall coat color (data not shown).
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). However, it was not until the sum of Phe + Tyr was 18 g/kg diet that a marked elevation of the concentration of tyrosine in plasma occurred. Values are also presented for redness score of the new hair grown in the clipped area in relation to plasma tyrosine concentration. The redness score for cats fed 18 g total aromatic amino acids/kg diet was 0, indicating the absence of red hairs. Below this dietary concentration, cats had increasing numbers of red hairs. The sum of the dietary concentration of Phe + Tyr was also positively related to the PTCA concentration in hair, but the relationship exhibited a discontinuity at 16 g/kg. In Figure 4
, the regression of dietary concentration of Phe + Tyr from 6 to16 g/kg diet on PTCA concentration in hair had a lower slope, (and a lower r2 value), than for dietary concentrations of 16–24 g/kg. The point of intersection of the two linear phases occurred between 16 and 18 g Phe + Tyr/kg diet.
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), there was a significant positive relationship (r2 = 0.87). This relationship indicates that plasma concentration of tyrosine was the prime determinant of the concentration of PTCA in hair and agrees with the relationship of the subjective visual assessment of red hairs in the newly grown hair in the shaved patches and concentration of plasma tyrosine presented in Figure 3
.
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). At concentrations of 10–16 g/kg diet, the ratio was essentially similar, but at a concentration 18 g of Phe + Tyr/kg diet, there was an increase in the ratio of PTCA to total melanin. This value coincided with the dietary concentration at which there was a change in visual assessment of hair color.
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Because all amino acids other than phenylalanine and tyrosine were present at 1.6–2 times the level recommended by the NRC (8
), the low dietary Phe + Tyr levels were limiting hair growth. Plasma tyrosine levels were as low as 4.4 ± 0.8 µmol/L in cats given the Phe + Tyr 4 + 2 g/kg diet. This is very low compared with cats in our colony given a commercial expanded diet (55 ± 4.7 µmol/L, n = 8). At this latter level of plasma tyrosine, cat hair remains visually black.
After 6 mo, three of the four male cats in group 1 receiving the Phe + Tyr 10 + 2 g/kg diet developed a neurological condition involving the posterior limbs and tail. On a slow walk, the cats had extended hind legs, resulting in an uncoordinated gait. The tail was held vertically, bending upward and forward over the back. On a fast walk, affected cats hopped on their hind legs. The most severely affected cat was hyperactive; it hypersalivated and emitted frequent vocalizations. Three affected cats were subjected to neurological examination. Conduction velocities of the peripheral nerves of the hind limbs were measured using evoked potentials. Two cats had 50% reductions in sensory nerve conduction velocity, but motor nerve conduction velocities were within the normal range. Histologic examination of nerve biopsies showed marked Wallerian degeneration of axons with secondary myelin collapse. A separate report will describe the neurological findings.
The most severely affected cat was transferred from the 10 + 2 g/kg diet to the 10 + 6 g/kg diet and within 1 mo, there was a marked improvement in hind limb coordination, vocalization was reduced and the hyperactivity disappeared. No adverse clinical signs were observed in cats given diets with phenylalanine + tyrosine concentrations 10 + 6 g/kg.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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) or AAFCO (10
). Because black hair color is determined by the proportion of the black-brown pigment eumelanin compared with the reddish brown pigment pheomelanin, it appears that genetically determined eumelanin synthesis in cats requires a higher concentration of Phe + Tyr in the diet than the concentration to maximize growth. Although both forms of melanin have a common precursor (L-tyrosine), eumelanin is derived from o-dihydroxyphenolic and indolic precursors alone, whereas pheomelanin is formed by the conjugation of reactive phenolic intermediates with L-cysteine, producing a benzothiazine intermediate. No studies on melanogenesis or its control have been done in cats; however, in other species, Ito (14
) reported an inverse relationship between the two forms of melanin and that the activity of tyrosinase controlled their relative proportions. Low activities of tyrosinase led to pheomelanin biosynthesis, whereas high tyrosinase activity led to eumelanin biosynthesis. A low activity of tyrosinase results in low levels of dopaquinone, which is converted to glutathionyldopa and to pheomelanin, whereas high activity of tyrosinase produces excess dopaquinone, which inhibits glutathione reductase and 
-glutamyl transpeptidase (enzymes required for pheomelanogenesis). L-Tyrosine is not only a precursor of melanin but also increases the activity of tyrosinase, thereby enhancing melanin synthesis (15
).
Using cultured melanocytes, it was shown (16
) that the pigmentation pattern changed with varying concentrations of cysteine and tyrosine in the media. High tyrosine and low cysteine concentrations favored eumelanogenesis. Because all of the diets we used contained the same concentrations of Met and Cys, the Cys pool in the plasma for the melanocyte should have been adequate, and similar in cats across all treatments. However, the concentration of tyrosine in plasma varied with the dietary Phe + Tyr concentration (Fig. 3)
and presumably the tyrosine pool available to the melanocytes reflected these changes. At low concentrations of dietary Phe + Tyr, the cysteine to tyrosine ratio in the pool would have favored pheomelanin synthesis and a greater proportion of "red hair." With <16 g/kg of Phe + Tyr, the concentration of tyrosine in the plasma increased only slowly with increasing Phe + Tyr, whereas above 16 g Phe + Tyr/kg diet, the rate of increase in tyrosine in plasma was accelerated as illustrated in Figure 3
. Coincidental with this increase in plasma tyrosine, the incidence of visually apparent "red hair" disappeared (Fig. 3)
. In addition, >16 g Phe + Tyr/kg diet led to a marked increase in the concentration of PTCA (an index of eumelanin) in hair (Fig. 4)
. This conclusion is further supported by the significant positive relationship between the concentration of plasma tyrosine and PTCA in hair (Fig. 5)
. Hair growth was also compromised by low dietary concentrations of Phe + Tyr. Although black cat hair contains 184 ± 2.4 µmol Phe and 247 ± 7.2 µmol Tyr/g lipid-free dry matter (17
), the loss from the body through hair is trivial [2.5 mg Phe + Tyr/(kg body weight · d)].
Tyrosine used for the synthesis of melanin may originate from plasma tyrosine or from phenylalanine after hydroxylation with phenylalanine hydroxylase (PH). As a measure of "potentially available tyrosine" to the follicular melanogenesis, we used the sum of dietary phenylalanine and tyrosine. However, studies using nonfeline melanocyte cultures indicated that phenylalanine may be a more efficiently used source of tyrosine for the follicular melanocyte than dietary tyrosine. Epidermal melanocytes express mRNA for PH in association with considerable enzyme activity. Cultured human epidermal melanocytes in the presence of L-phenylalanine produce 40% more melanin than an equivalent concentration of L-tyrosine (18
). The transport of extracellular L-phenylalanine and its intracellular metabolism to L-tyrosine by PH are coupled with calcium transport, whereas L-tyrosine uptake by melanocytes is calcium independent. The cofactor for PH, 6(R)-L-erythro 5,6,7,8, tetrahydrobiopterin, is produced de novo and is recycled and regulated in melanocytes and keratinocytes to control tyrosine hydroxylase, PH and tyrosinase activity (19
).
The considerably greater dietary intake of Phe + Tyr required to maintain black hair in cats than for maximal growth is consistent with the apparent Km values reported for reactions involving tyrosine. The Km of the acyl synthetase is 4 x 10-5 mol/L (20
), whereas the catabolic enzyme (tyrosine aminotransferase) is 375 times greater (1.5 x 10-3 mol/L) (21
). Tyrosinase is the key enzyme that controls the biosynthesis of melanin (22
). A range of apparent Km values for tyrosinase from murine melanomas has been recorded. In one study, the apparent Km values for tyrosine and DOPA were 7 x 10-4 and 6 x 10-4 mol/L, respectively (23
), and in a subsequent study, apparent Km values of two isoenzymes of tyrosinase for tyrosine were 1.2 x 10-4 and 2.3 x 10-4 mol/L (24
). Km values reported for tyrosinase isolated from cephalopod ink were higher (1.7 x 10-4 and 10 x 10-3 mol/L, respectively) for L-tyrosine and L-DOPA (25
). The mammalian Km value of tyrosinase for tyrosine indicates that the concentration of tyrosine for melanin synthesis would have to be 3 to 17 times higher than that required for growth.
Our study demonstrating that melanin in cat hair was positively related to the concentration of dietary tyrosine with a constant (10g/kg) phenylalanine concentration, does not support the conclusions of Schallreuter (19
) who asserted that "the active transport of L-phenylalanine and its autocrine turnover to L-tyrosine via PH in the cytosol of the epidermal human melanocyte provides the majority of the L-tyrosine pool for melanogenesis."
The observation that the clinical signs of hyperactivity and ataxia resolved or were reduced after the most severely affected cats were given the 10 + 6 g/kg diet suggests the involvement of tyrosine in catecholamine production rather than structural nerve degeneration. In catecholamine synthesis, the conversion of tyrosine to DOPA is catalyzed by tyrosine hydroxylase, which is the rate-limiting enzyme of the pathway. Isolates of the enzyme from the preoptic region and hypothalamus of rats both gave apparent Km values of 8 x 10-5 mol/L for tyrosine (26
,27
), which is considerably lower than the Km for tyrosinase, but about twice the Km of the acyl synthetase. Other factors in addition to the Km value, such as transport, may have a role in determining catecholamine synthesis. Tyrosine deficiency is manifested in multiorgan systems, including a reduction in hair growth and follicle density, hair color and peripheral sensory neuropathy, which is probably related to the origin in the vertebrate embryo of the skin melanocytes and hair bulbs in the neural crest (28
).
Red coat has been described in dogs and cats given certain commercial and therapeutic foods. However, reports of its occurrence have been mainly anecdotal, such that it has generally been considered to be a myth or "an old wives tale" (29
). The present study indicates that eumelanin production in cats is compromised if the sum of readily available dietary Phe + Tyr is <16 g/kg diet. We recommend that the dietary phenylalanine plus tyrosine requirement be increased to at least 18 g of available aromatic amino acids/kg diet to maintain black hair color in cats. As a diagnostic aid, a plasma tyrosine concentration of >50 µmol/L is necessary to prevent "red hair" in cats.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: AAFCO, Association of American Feed Control Officials; DAA, dispensable amino acid; DOPA, dihydroxyphenylalanine; EAA, essential amino acid; PH, phenylalanine hydroxylase; PTCA, pyrrole-2,3,5-tricarboxylic acid; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone.
Manuscript received 12 December 2001. Initial review completed 19 January 2002. Revision accepted 18 March 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSExperimental designRESULTSDISCUSSIONLITERATURE CITED |
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1. Ortonne, J.-P. & Prota, G. (1993) Hair melanins and hair color: ultrastructural and biochemical aspects. J. Investig. Dermatol. 101(Suppl.):82S-89S.[Medline]
2. Ozeki, H., Ito, S., Wakamatsu, K. & Hirobe, T. (1995) Chemical characterization of hair melanins in various coat-color mutants of mice. J. Investig. Dermatol. 105:361-366.[Medline]
3. Morris, J. G., Yu, S. & Rogers, Q. R. (2002) Red hair in black cats is reversed by the addition of tyrosine to the diet. J. Nutr. 132(in press)..
4. Kobayashi, T., Viera, W. D., Potterf, B., Sakai, C., Imokawa, G. & Hearing, V. J. (1995) Modulation of melanogenic protein expression during the switch from eu- to pheomelanogenesis. J. Cell Res. 108:2301-2309.
5. Cowie, V. & Penrose, L. S. (1951) Dilution of hair colour in phenylketonuria. Ann. Eugen. 16:297-301.
6. Rogers, Q. R. & Morris, J. G. (1979) Essentiality of amino acids for the growing kitten. J. Nutr. 109:718-723.
7. Anderson, P. A., Baker, D. H., Sherry, P. A. & Corbin, J. E. (1980) Histidine, phenylalanine-tyrosine requirements for growth of the young kitten. J. Anim. Sci. 50:479-483.
8. Williams, J. M., Morris, J. G. & Rogers, Q. R. (1987) Phenylalanine requirement of kittens and the sparing effect of tyrosine. J. Nutr. 117:1102-1107.
9. National Research Council (1986) Nutrient Requirements of Cats 1986 National Academy Press Washington, DC. .
10. Association of American Feed Control Officials (2001) Official Publication 2001 American Feed Control Officials .
11. Yu, S., Rogers, Q. R. & Morris, J. G. (2001) Effect of low levels of dietary tyrosine on the hair colour of cats. J. Small Anim. Prac. 42:176-180.
12. National Research Council (1996) Guide for the Care and Use of Laboratory Animals 1996 National Academy Press Washington, DC. .
13. Ito, S. & Wakamatsu, K. (1998) Chemical degradation of melanins: application to identification of dopamine-melanin. Pigm. Cell Res. 11:120-126.[Medline]
14. Ito, S. (1993) High performance liquid chromatography. (HPLC) analysis of eu- and pheomelanin in melanogenesis control. J. Investig. Dermatol. 100:166S-171S.[Medline]
15. Slominski, A., Moellmann, G., Kuklinska, E., Bomirski, A. & Pawelek, J. (1988) Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. J. Cell. Sci. 89:287-296.
16. Smit, N.P.M., Van der Meulen, H., Koerten, H. K., Kolb, R. M., Mommaas, A. M., Lenjes, E.G.W.M. & Pavel, S. (1997) Melanogenesis in cultured melanocytes can be substantially influenced by L-tyrosine and L-cysteine. J. Investig. Dermatol. 109:796-800.[Medline]
17. Hendriks, W. H., Tarttelin, M. F. & Moughan, P. J. (1996) Protein Metabolism in the Adult Domestic Cat (Felis catus) 1996:117 Doctoral thesis, Massey University Palmiston North, New Zealand. .
18. Schallreuter, K. U. & Wood, J. M. (1999) The importance of phenylalanine transport and its autocrine turnover of L-tyrosine for melanogenesis in human epidermal melanocytes. Biochem. Biophys. Res. Commun. 262:423-428.[Medline]
19. Schallreuter, K. U. (1999) A review of recent advances on the regulation of pigmentation in the human epidermis. Cell. Mol. Biol. (Noisy-Le-Grand) 45:943-949.
20. Clark, J. M. & Eyzaguirre, J. P. (1962) Tyrosine activation and transfer to soluble ribonucleic acid. 1 Purification and study of the enzyme of hog pancreas. J. Biol. Chem. 237:3698-3702.
21. Litwack, G., Winicov, I. & Squires, J. M. (1966) The effect of pH on the rat liver tyrosine aminotransferase system. Biochim. Biophys. Acta 128:404-406.[Medline]
22. Pawelek, J. M. & Chakraborty, A. K. (1998) The enzymology of melanogenesis. Nordlund, J. J. Boissy, R. E. Hearing, V. J. King, R. A. Ortonne, J-P. eds. Pigmentary System 1998:391-400 Oxford University Press New York, NY. .
23. Laskin, J. D. & Piccinini, L. A. (1986) Tyrosinase isozyme heterogeneity in differentiating B16/C3 melanoma. J. Biol. Chem. 261:16626-16635.
24. Jimenez-Cervantes, C., Garcia-Borron, J. C., Valverde, P., Solano, F. & Lozano, A. (1993) Tyrosinase isoenzymes in mammalian melanocytes 1. Biochemical characterization of two melanosomal tyrosinases from B16 mouse melanoma. Eur. J. Biochem. 217:549-556.[Medline]
25. Prota, G. (1976) Melanins and Melanogenesis 1976:38 Academic Press San Diego, CA. .
26. Perez, E., Amici, R., Bacchelli, B., Zamboni, G., Libert, J. P. & Parmeggiani, P. L. (1987) Kinetic parameters of tyrosine hydroxylase in the rat’s preoptic region during sleep deprivation and recovery induced by ambient temperature. Sleep 10:436-442.[Medline]
27. Philipp, E. (1987) Assay for tyrosine hydroxylase in hypothalamic homogenates using high-performance liquid chromatography with electrochemical detection. J. Chromatogr. 419:27-36.[Medline]
28. Schraemeyer, U. (1996) The intracellular origin of the melanosome in pigment cells. A review of ultrastructural data. Histol. Histopathol. 11:445-462.[Medline]
29. Case, L. P., Carey, D. P., Hirakawa, D. A. & Daristotle, L. (2000) Common nutrition myths. Canine and Feline Nutrition 2000:359-361 Mosby St. Louis, MO. .
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