Taurine: An Essential Nutrient for the Cat1

Abstract

Cats fed a purified diet containing purified casein as the source of protein develop retinal degeneration due to the lack of taurine in the diet. To test whether cats can synthesize this sulfur amino acid from sulfate or cystine, radioisotopes of these substances were injected into taurine-depleted and control cats. Sulfate did not serve as a precursor for taurine synthesis, whereas cystine underwent only a moderate conversion to taurine. This is in keeping with the low level of cysteinesulfinic acid (CSA) decarboxylase activity in cat liver. There was no difference between the activity of CSA decarboxylase in tissues from control cats and that in tissues from taurine-depleted cats. The pattern of tissue accumulation of [35S]taurine and from [35S]cystine also indicated that tissues from taurine-depleted cats do not synthesize [35S]taurine more rapidly than tissues from control cats. The data did not indicate a difference in taurine uptake by tissues of control and deficient cats, but progressive accumulation in deficient cats suggested that the turnover rate of taurine is decreased by the deficiency. Since supplementation of the purified diet with cysteine has been found previously to be inadequate to prevent progressive taurine depletion of the retina and its subsequent degeneration and since conversion of sulfur compounds to taurine in vivo is inadequate, taurine can be considered an essential nutrient for the cat.

Full text

Taurine: An Essential Nutrient for the Cat1
KAREN KNOPF, J. A. STURMAN,
MARCIA ARMSTRONG ANDK. C. HAYES
Department of Nutrition, Harvard School of Public
Health, Boston, Massachusetts 02115 and Division of
Human Development and Genetics, Institute for Basic
Research in Mental Retardation, Staten Island, New
York 10314 and Department of Pediatrics, Mount Sinai
School of Medicine of the City University of New York,
New York, New York 10029
ABSTRACT Cats fed a purified diet containing purified casein as the
source of protein develop retinal degeneration due to the lack of taurine
in the diet. To test whether cats can synthesize this sulfur amino acid from
sulfate or cystine, radioisotopes of these substances were injected into
taurine-depleted and control cats. Sulfate did not serve as a precursor for
taurine synthesis, whereas cystine underwent only a moderate conversion
to taurine. This is in keeping with the low level of cysteinesulfinic acid
(CSA ) decarboxylase activity in cat liver. There was no difference between
the activity of CSA decarboxylase in tissues from control cats and that in
tissues from taurine-depleted cats. The pattern of tissue accumulation of
[35S]taurine and from [35S]cystine also indicated that tissues from taurine-
depleted cats do not synthesize [35S]taurine more rapidly than tissues from
control cats. The data did not indicate a difference in taurine uptake by
tissues of control and deficient cats, but progressive accumulation in de
ficient cats suggested that the turnover rate of taurine is decreased by the
deficiency. Since supplementation of the purified diet with cysteine has
been found previously to be inadequate to prevent progressive taurine
depletion of the retina and its subsequent degeneration and since conver
sion of sulfur compounds to taurine in vivo is inadequate, taurine can be
considered an essential nutrient for the cat. J. Nutr. 108: 773-778, 1978.
INDEXING KEY WORDS taurine •essential nutrients •cats •
cysteine
It has been demonstrated in a series of not convert to glycine as occurs in other
studies that cats fed synthetic, diets con- species. Instead, the concentration of free
taining purified casein as the source of cholic acid increases—an increase that is
protein develop retinal degeneration which less marked in adult cats than in kittens
results from progressive depletion of retinal (3 ).
taurine. Supplementing this diet with These observations suggest that the cat,
taurine, but not with methionine or with and particularly the kitten, is incapable of
cysteine, maintained the retinal taurine synthesizing sufficient taurine to meet the
concentration and prevented the degenera-
tion from developing (1, 2). Furthermore, Received for publication December 22, 1976.
the bile acids of the Cat are Conjugated »Supported in part by grants-in-ald from the
exclusively with taurine and, under condì- ^SS^Sf^SftÃ-Sff^^SIS^ SñSSÕ
tions Of taurine depletion during feeding of Harvardjcnoo^of B^McJBtoatt (Haye^, and^the
such a casein diet, this conjugation does (sturman).
773
by guest on July 10, 2011jn.nutrition.orgDownloaded from

774 KNOPF, STURMAN, ARMSTRONG AND HAYES
requirements for maintaining retinal func
tion and structure, making taurine an es
sential nutrient in this species. All species
are thought to convert methionine to tau
rine via cysteine and cysteinesulfinic acid
(CSA), although considerable variation in
the activity of CSA decarboxylase, the en
zyme directly responsible for the synthesis
of taurine, has been reported in different
species (4). Rats (5) and chicks (6) are
able to convert inorganic sulfate to taurine
in vivo, presumably by activation to 3'-
phosphoadenosine-5'-phosphosulfate (PAPS)
and transfer of the sulfate to serine by
PAPS-sulfotransferase. Other species also
may be able to form taurine by this route,
since activity of PAPS-sulfotransferase has
been found in all species so far investigated
including the cat (7). According to these
authors the enzymatic mechanism for syn
thesizing taurine in vitro from inorganic
sulfate is present in the heart and liver of
the cat as well as in the heart and liver of
the chick, dog, guinea pig, hamster, mon
key, mouse, rabbit, rat and sheep. The hy
pothesis is advanced by these authors that
"regardless of diet or anatomical differ
ences, this enzyme appears to be a com
ponent of all animal tissues." We have
studied the possibility of conversion of in
organic sulfate and cystine to taurine in the
cat and report the results in this communi
cation.
MATERIALS AND METHODS
Kittens obtained from random sources
and of the domestic variety, ranging in
weight from 1,100 to 1,600 g, were fed a
purified casein diet (3, 8) alone or supple
mented with 0.4% taurine or 0.6% sulfate
for periods of TA weeks or 15 weeks from
6 weeks of age. The casein diet contained
(calculated in g/100 g): methionine, 0.5;
cystine, 0.1; taurine, 0.0. The cats were
killed and blood samples obtained using
heparin as anticoagulant. Samples of urine
were obtained from the bladder and the
following tissues removed: liver, heart,
gastrocnemius muscle, retina, occipital lobe
and cerebellum. Plasma, urine and tissues
were prepared for amino acid analysis and
the concentration of taurine determined
(9).
Seven other cats were fed the casein diet
alone or the casein diet supplemented with
taurine. Three cats were killed 5 days after
the intravenous injection of 1 ml of saline
containing 2.87 mCi/ml [35S]sulfate2 (di-
sodium salt, specific activity 969 mCi/
mmole) (two fed the casein diet, one the
casein diet supplemented with taurine).
Four cats were killed 24 hours or 14 days
after injection of 1 ml of saline containing
2.14 mCi/ml [35S]cystine 3 (specific activity
88.2 mCi/mmole) (one fed the casein diet
and one the casein diet supplemented with
taurine at each time). Tissues were re
moved and analyzed for taurine and [36S]-
taurine as previously described (9). In
addition, bile samples were collected and
analyzed for bile acids (3) and the pres
ence of 35Sas sulfate or taurine. Bile acids
were subjected to solvolysis to remove sul
fate (10, 11) and separated into a water-
soluble sulfate fraction, a dichloromethane
fraction containing the cleaved bile acids,
and a diethyl ether fraction containing
residual uncleaved bile acids. Radioactivity
in each fraction was measured using a
liquid scintillation counter.*
The activity of CSA decarboxylase in
liver, occipital lobe and cerebellum of cats
fed the casein diet or the casein diet sup
plemented with taurine was determined as
previously described (12).
RESULTS
The addition of sulfate to the casein diet
had no effect on the concentration of tau
rine in any of the tissues studied. In addi
tion, since there was no significant differ
ence between the concentration of taurine
in the tissues of cats fed the casein diet for
7% weeks and those fed the diet for 15
weeks, all of the data are pooled accord
ing to diet—casein versus casein supple
mented with taurine. The concentration of
taurine is smaller in all of the tissues
studied from the cats fed the casein diet
than in the same tissues from the cats fed
the casein diet supplemented with taurine
(table 1). The greatest depletion occurs
in liver (almost 100-fold) and the smallest
*New England Nuclear. Cambridge, Massachusetts.
3Amergham/Searle Corp., Chicago, Illinois.
'Model LS-250, Beck Instruments Company.
by guest on July 10, 2011jn.nutrition.orgDownloaded from

TAURINE IN CATS 775
occurs in retina (2-fold). Taurine is not
detectable in most plasma samples from
cats fed the casein diet and the concentra
tion of taurine in the urine of these cats is
200-fold lower than in urine of control cats.
No conversion of [35S]sulfate to [35S]-
taurine in vivo could be detected in any
tissue of the control or taurine-depleted
cats despite the large amounts of radio
active sulfate injected. Even in urine,
where samples analyzed contained in excess
of IO6dpm, no trace of radioactive taurine
was detected (the analytical system used
can detect as little as 200 dpm above back
ground). Both plasma and urine contained
another 35S-labeled compound, eluted in
the same position as sulfate, but not pre
cipitated by BaClg. In plasma this com
pound comprised 40% of the radioactivity
in the samples and in urine 1% of the
radioactivity in the samples. No further
attempt was made to identify this com
pound since it clearly was not taurine (in
this analytical system, inorganic sulfate is
eluted virtually with the solvent front and
a further 20 ml of buffer are needed to
elute taurine). Radioactivity was present
TABLE 1
Concentration of taurine in various tissues of cats
fed the casein diet or the casein diet
supplemented with taurine
Casein
Tissue Casein + Taurine
itmole/g wet wt.
Liver 0.21±0.03 18.87±5.08
Heart 1.18±0.18 17.57±2.08
Gastrocnemius
muscle
Retina
Occipital lobe
Cerebellum1.54
±0.29
17.88±2.03
0.29±0.05
0.45±0.067.42
±0.95
32.10±3.46
2.90±0.20
4.30±0.22/¡mole/mlPlasma
Urine<0.01 0.06±0.030.11 ±0.02
11.02±2.48
These values represent the mean±SEM/¿mole
taurine/g wet weight of tissue or per ml plasma or
urine from 19 cats fed the casein diet, or from eight
cats fed the casein diet supplemented with taurine.
The values for taurine concentration in tissues and
fluids of the cats fed casein diet alone are all signifi
cantly different from the values for taurine con
centration in the same tissues and fluids of the cats
fed the casein diet supplemented with taurine as
determined by Students f-test (P < 0.001).
TABLE 2
Bile taurine concentration and radioactivity 5 days
after injection of cats with [3*S]sulfate
Diet
Bile taurine1 Casein
Casein -f-Taurine
Concentration
(/imole/ml)Radioactivity2(IO3
dpm/ml)Specific
activity(IO3
dpm//umole)98.7,
121.40.0,0.0,0.00.086.00.00.0
1Derived from taurine conjugated bile acids
following solvolysis (10, 11). 2The samples con
taining taurine did not have any radioactivity above
that of background. Each value was derived from
one cat.
in bile acids, but was essentially completely
removed by solvolysis indicating that it
represented direct sulfation of the bile
acid sterol nucleus and not incorporation
of label into taurine (10) (table 2).
[35S]Cystine was converted to [35S]tau-
rine in vivo and found in easily measured
quantities in liver, heart and retina (table
3). Trace amounts of radioactive taurine
were detected in urine, plasma and brain
from the cats fed the casein diet supple
mented with taurine, but not from the cats
fed the casein diet alone. There were some
differences between the amounts of 35S
taurine formed in the cats fed the casein
diet and those fed the casein diet supple
mented with taurine. After injection of
TABLE 3
Radioactivity in taurine after injecting [3SiS]ct/s<ine
into four cats fed the casein diet or the casein
diet supplemented with taurine
Tissue and
timeafterinjectionRadioactivityCaseinCasein+
Taurine10'
dpm/gLiver24
hours14
daysHeart24
hours14
daysRetina24
hours14
days<0.50<0.503.7917.418.4227.7831.263.625.525.057.838.42Specific
ActivityCaseinCasein
+Taurinedpm
limole0
16100
2896011
3159619
191884
2882179 77
Each value was derived from one cat.
by guest on July 10, 2011jn.nutrition.orgDownloaded from

776 KNOPF, STURMAN, ARMSTRONG AND HAYES
TABLE 4
Bile taurine concentration and radioactivity after
injecting [3SS~]cystineinto cats fed the casein diet
or the casein diet supplemented with taurine
Bile taurine1
and time
after injection Casein Casein
+ Taurine
Concentration Gimole/ml)
24 hours 47.8
14 days 124.8
Radioactivity (IO3dpm/ml)
24 hours 498
14 days 1612
Specific activity (IO3dpm//imole)
24 hours 10.4 1.7
14 days 12.9 0.3
123.5
109.0
209
32
1See footnote in table 2.
rived from one cat. Each value was de-
[35S]cystine, [35S]taurine could not be de
tected in liver from the cats fed the casein
diet, whereas it was readily measured in
the liver of cats fed the casein diet sup
plemented with taurine. There was little
difference in total radioactivity in taurine
in heart and retina after 24 hours between
the cats fed the casein diet or the casein
diet supplemented with taurine, and only
a 2-fold difference in radioactivity in bile
(table 4). The radioactive taurine in heart
and retina of the cats fed the casein diet
supplemented with taurine was unchanged
after 14 days but accumulated in heart and
retina of the cats fed the casein diet. Thus,
after 14 days the heart and retina of these
cats contained more than 3 times the
amount of [35S]taurine than was present
in these same tissues of cats fed the casein
diet supplemented with taurine (table 3).
After 14 days the bulk of the radioactivity
in extracts of liver and heart was present
as taurine and all of the radioactivity in
extracts of retina was present as taurine.
The radioactivity in bile acids from cats
fed the casein diet supplemented with
taurine decreased 7-fold from 24 hours to
14 days after injection of [35S]cystine,
whereas it increased 3-fold in the cats fed
the casein diet over this period. Thus, 14
days after injection of [35S]cystine, there
was approximately 50-fold more radio
active taurine conjugated to bile acids in
TABLE 5
Activity of cysfeine sulfinic acid decarboxytase in liver
and brain of cats fed the casein diet or the casein
diet supplemented with taurine
Casein
Tissue Casein + Taurine
limole COì/mgprotein/hr
Liver 4.4 ±0.4 4.5 ±0.4
Occipital lobe 58.8±2.3 52.1 ±5.5
Cerebellum 55.1±2.1 49.8±2.8
Each value represents the mean±SEM from
three cats fed the casein diet or the casein diet
supplemented with taurine. The values for tissues
from cats fed the casein diet alone are not signifi
cantly different from the values for the same tissues
from cats fed the casein diet supplemented with
taurine as determined by Student's i-test.
cats fed the casein diet alone than to bile
acids in those cats fed the casein diet sup
plemented with taurine (table 4). Solvoly-
sis and separation and counting of fractions
indicated that the 35S cystine was exclu
sively incorporated as taurine conjugated
bile acids.
There was no difference in CSA decar-
boxylase activity in liver, occipital lobe and
cerebellum from cats fed the casein diet
alone or supplemented with taurine (table
5). Activity in liver was low compared to
that in brain and the values obtained are
similar to those previously reported (4 ).
DISCUSSION
These results provide evidence that cats
fed a synthetic diet containing purified
casein as the source of protein have a de
creased concentration of taurine in a wide
variety of tissues. They show further that
the addition of sulfate to such a diet has
no effect on the concentration of taurine in
any of the tissues, and that sulfate is not
converted to taurine in the cat. Taurine was
formed in limited amounts from cystine;
its formation presumably being limited by
the low activity of CSA decarboxylase
present. The formation of taurine from
cystine did not appear to be enhanced by
taurine depletion since the activity of CSA
decarboxylase was similar for both dietary
groups. Furthermore, since the amount of
radioactive taurine present in heart and
retina after 24 hours was similar, the forma
tion and/or uptake of [35S]taurine by these
by guest on July 10, 2011jn.nutrition.orgDownloaded from

TAURINE IN CATS 777
tissues in the control and taurine-déficient
cats was similar. The difference in specific
activity of [35S]taurine between the tissues
of the taurine-déficientand control cats is
the result of the differences in concentra
tion of taurine between those same tissues.
Thus, taurine deficiency does not appear
to influence the formation of taurine from
cystine. However, the low activity of CSA
decarboxylase in liver of the cats makes it
likely that because synthesis of taurine is
limited, any effect on uptake of taurine is
obscured. The inability to detect radio
active taurine in liver of cats fed the casein
diet alone may have been due to the result
either of the small amount of endogenous
taurine present in liver to trap any labeled
taurine or of the immediate utilization of
any taurine (labeled or not) for conjuga
tion with bile acids.
By 14 days after the injection of [35S]-
cystine, there were other differences found
between cats fed the casein diet alone and
the casein diet supplemented with taurine
in the behavior of [35S]taurine. Thus
[35S]taurine continued to accumulate in
heart, retina and bile of the taurine-défi
cient cats but not in those tissues from the
control animals. This accumulation may
have resulted from the remaining taurine
having a slower rate of turnover in the tis
sues of the deficient cats than it did in the
tissues of the control cats.
It is possible also that the amounts of
[35S]taurine accumulated by the various
tissues in the taurine-déficientcats reflect
the importance of taurine for the function
of that tissue. On this basis bile acids would
have the most important functional need
for taurine, followed by the retina and
heart. Interestingly, [35S]taurine was not
detected in the occipital lobe or cerebellum
from either control or taurine-déficientcats.
Apparently the remaining 10% of taurine
in brain tissue is adequate for vital control
of central nervous system functions. Other
studies have suggested also that only a
small fraction of the total amount of taurine
in brain is associated with synaptic ves
icles (13).
These results support the concept that
taurine is an essential nutrient for the cat.
Further evidence has recently been re
ported from two independent laboratories.
The first demonstrated that the isolated
perfused cat liver, unlike the rat liver, was
incapable of maintaining taurine synthesis
for bile acid conjugation (14). The second
found that the retinal dysfunction was still
apparent when a purified amino acid mix
ture without taurine was substituted for
the dietary casein (15). In essence, taurine
must be supplied by the diet to prevent
depletion of retinal taurine and the im
paired visual function and structure that
results from its depletion. Under normal
circumstances cats do consume foods which
are rich sources of taurine, such as fish and
meat (16). The present data indicate that
the cat can convert a limited amount of
cystine to taurine; however, it was demon
strated previously that replacing dietary
taurine with equimolar amounts (0.8%) of
cystine (or methionine) failed to maintain
normal body concentrations of taurine, par
ticularly the plasma and retinal pools. This
occurred despite elevated plasma levels of
methionine and cysteine. Those kittens
eventually developed retinal degeneration
(2), clearly indicating that the ability to
convert cysteine (or methionine) to tau
rine was not adequate to meet at least one
important physiological need, i.e., that re
quired for vision. The fact that the cat is
unable to utilize sulfate as a source of
taurine further indicates this species de
pendence on a dietary supply of taurine
and the essentiality of this compound for
the cat.
These dietary studies in cats have as
sumed added significance in light of re
ports that human infants fed a mükformula
based on casein have appreciably lower
serum and urinary taurine concentrations
than breast-fed infants (17, 18). Whether
the human neonate has a poorly developed
enzyme capability for synthesis of taurine
remains to be determined.
ACKNOWLE DOME NT
The authors thank Ms. Judith Fagan and
Mr. Barry Rabin for expert technical as
sistance.
LITERATURE CITED
1. Hayes, K. C. (1976) A review of the bio
logical function of taurine. Nutr. Rev. 34,
161-165.
by guest on July 10, 2011jn.nutrition.orgDownloaded from

778 KNOPF, STURMAN, ARMSTRONG AND HAYES
2. Berson, E. L., Hayes, K. C., Rabin, A. R.,
Schmidt, S. Y. & Watson, G. (1976) Retinal
degeneration in cats fed casein. II. Supple
mentation with methionine, cysteine, or
taurine. Invest. Ophthalmol. 15, 52-58.
3. Rabin, B., Nicolosi, R. J. & Hayes, K. C.
( 1976 ) Dietary influence on bile acid con
jugation in the cat. J. Nutr. 106, 1241-1246.
4. Jacobsen, J. G., Thomas, L. L. & Smith, L. H.,
Jr. ( 1964 ) Properties and distribution of
mammalian L-cysteine sulfinate carboxylases.
Biochim. Biophys. Acta 85, 103-116.
5. Martin, W. G., Sass, N. L., Hill, L., Tarka, S.
& Truex, R. (1972) The synthesis of taurine
from sulfate. IV. An alternate pathway for
taurine synthesis by the rat. Proc. Soc. Exp.
Biol. Med. 141, 632-633.
6. Hill, L. & Martin, W. G. (1973) The syn
thesis of taurine from sulfate. V. Regulatory
modifiers of the chick liver enzyme system.
Proc. Soc. Exp. Biol. Med. 144, 530-533.
7. Martin, W. G., Truex, C. R., Tarka, M., Hill,
K. J. & Gorby, W. G. ( 1974) The synthesis
of taurine from sulfate. Vili. A constitutive
enzyme in mammals. Proc. Soc. Exp. Biol.
Med. 147, 563-565.
8. Hayes, K. C., Rabin, A. R. & Berson, E. L.
(1975) An ultrastructural study of nutri
tionally induced and reversed retinal degen
eration in cats. Am. J. Pathol. 78, 505-516.
9. Sturman, J. A. (1973) Taurine pool sizes
in the rat: Effects of vitamin B-6 deficiency
and high taurine diet. J. Nutr. ¿03, 1566-
1580.
10. Palmer, R. H. & Bolt, M. G. (1971) Bile
acid sulfates. I. Synthesis of lithocholic acid
sulfates and their identification in human bile.
J. Lipid Res. 12, 671-679.
11. Kornel, L. (1965) Studies on steroid con
jugates. IV. Demonstration and identification
of solvolyzable corticosteroids in human urine
and plasma. Biochemistry 4, 444-452.
12. Rassin, D. K. & Gaull, G. E. (1975) Sub
cellular distribution of enzymes of trans-
methylase and transulfurylase in rat brain. J.
Neurochem. 24, 969-978.
13. Rassin, D. K., Sturman, J. A. & Gaull, G. E.
(1977) Taurine in the developing rat: Sub-
cellular distribution and association with
synaptic vesicles of ^S-taurine in maternal,
fetal and neonatal rat brain. J. Neurochem.
28, 41-50.
14. Hardison, W. G. M., Wood, C. A. & Proffitt,
J. H. (1977) Quantification of taurine syn
thesis in the intact rat and cat liver. Proc.
Soc. Exp. Biol. Med. 155, 55-58.
15. Schmidt, S. Y., Berson, E. L., Watson, G. &
Huang, C. (1977) Retinal degeneration in
cats fed casein. III. Taurine deficiency and
ERG amplitudes. Invest. Ophthalmol. Vis.
Sci. 16, 673-678.
16. Roe, D. A. & Weston, W. O. (1965) Po
tential significance of free taurine in the diet.
Nature 204, 287-288.
17. Gaull, G. E., Rassin, D. K., Heinonen, K. &
Räihä,N. C. R. (1977) Milk protein quan
tity and quality in low-birth-weight infants:
II. Effects on selected aliphatic amino acids
in plasma and urine. J. Pediat. 90, 348-355.
18. Rigo, J. & Senterre, J. (1977) Is taurine
essential for the neonates? Biol. Neonate 32,
73-76.
by guest on July 10, 2011jn.nutrition.orgDownloaded from