Experiments That Changed Nutritional Thinking - TUUM EST

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liver rose dramatically but the yellow units were only modestly
increased. Fresh carrots, given ad libitum to the animals,
TABLE 1
showed a similar effect.
Bisulfite-binding substances from normal and
Moore then made the following calculation. Because the
ratio of yellow to blue units for b-carotene is 11 to 1, the
vitamin B1–deficient pigeons and rats1
number of yellow units of carotene corresponding to the blue
units found in the liver (2000–3700) when large doses of
carotene were given would be expected to be 22,000–41,000.
Animal Normal Deficient
mg/100 mL blood
Cured
The amount of yellow units actually present, however, was
Pigeon 3.96 11.31
only 40–110 (Table 1), a very small fraction of the amount
Rat 4.22 9.39
expected to support an active role of carotene per se. Thus,
5.29
Moore (1930) concluded: ‘‘It is impossible that the colour
1 Data from Thompson and Johnson (1935). Approximately 2.5 mg
reaction of carotene could conceal any underlying colour reac- of each averaged number is not pyruvate.
tion due to the liver oil vitamin A in such amounts as would
account for its physiological activity. The conclusion must be
reached that carotene, or some part thereof, if it should later Peters 1929 and 1930) also concluded that there was more
prove to be heterogeneous, behaves in vivo as a precursor of lactic acid present in the brains of pigeons showing acute
the vitamin.’’
symptoms of vitamin B1 deficiency. R. B Fisher (1931) further
Soon thereafter, Karrer et al. (1931) determined the chemi- noted the slower loss of lactate from heart and skeletal muscle
cal structures both of carotene and of vitamin A. Karrer’s of deficient pigeons after exercise.
structural determinations were in full accord with Moore’s Peters and associates then demonstrated that adding thiaconclusions.
Thus, the dilemma of the relationship between min (in concentrated form) to brain tissue from deficient pithe
colored compounds largely found in plant foods and the geons, with added lactate, increased the in vitro rate of oxygen
nearly colorless compounds of liver had been resolved. Need- consumption to that of tissue from normal birds (Meiklejohn et
less to say, Moore’s findings have stood the test of time. al. 1932). Two years later it was shown that adding crystalline
thiamin also increased the metabolism of added pyruvate (Peters
and Thompson 1934). This made an immediate metabolic
Literature Cited
connection to carbohydrate metabolism whereby glucose had
Karrer, P., Morf, R. & Schoepp, K. (1931) Zur kenntnis des vitamins A in fischrecently
been shown by Embden and Meyerhof to be degraded
tranen. Helv. Chim. Acta 14: 1431–1436.
McCollum, E. V. & Davis, M. (1913) The necessity of certain lipins during in animals to pyruvate. However, the lack of a significant
growth. J. Biol. Chem. 15: 167–175.
difference between pyruvate content of normal and vitamin
Moore, T. (1930) LXXIX. Vitamin A and carotene. V. The absence of the liver
B1–deficient brains before incubation with added lactate was
oil vitamin A from carotene. VI. The conversion of carotene to vitamin A in
vivo. Biochem. J. 24: 692–702.
puzzling.
Osborne, E. V. & Mendel, L. B. (1913) The relation of growth to the chemical The explanation was provided by the work of R.H.S.
constituents of the diet. J. Biol. Chem. 15: 311–326.
Thompson and R. E. Johnson (1935), who correctly supposed
Palmer, L. S. & Kempster, H. L. (1920) Relation of plant carotenoids to growth,
fecundity and reproduction of fowls. J. Biol. Chem. 39: 299–313.
that the abnormally large amount of pyruvate formed in the
Steenbock, H. (1919) White corn vs. yellow corn and a probable relationship deficient brain in vivo was not detectable because the metabobetween
the fat-soluble vitamine and yellow plant pigments. Science 50: 352– lite largely diffuses out into the blood stream. Using pigeons
353.
and rats, they measured pyruvate indirectly with other keto
compounds that can form bisulfite complexes, and they secured
Paper 12: The Co-enzyme Function of the fractional amount of pyruvate in the bisulfite-binding compounds
by direct isolation of the pyruvate 2,4-dinitrophenylhy-
Thiamin (Peters et al., 1929–1937)
drazone and estimating it colorimetrically. Their findings are
Presented by Donald B. McCormick, Department of Biochemistry, summarized in Table 1. It should be noted that Platt and Lu
Emory University School of Medicine, Atlanta, GA 30322 as part (1935) bridged from the experimental animals to humans by
of the minisymposium ‘‘Experiments That Changed Nutritional concordantly reporting the presence of pyruvate in the blood
Thinking’’ given at Experimental Biology 95, April 11, 1995, in and cerebrospinal fluid of beriberi patients in the Orient, where
Atlanta, GA.
the story began.
The significance of findings importantly focused by the investigators
Descriptions of a particular human illness that were recorded
at Oxford, and even the broader value of basic
over a thousand years ago in the Far East reflect what research with its use of animals, was well reviewed by R. A.
later was termed beriberi (Gubler 1991, McCormick 1988). Peters (1936) in his lecture delivered at the National Hospital,
Eijkman and then Grijns, working in Batavia, used chickens Queen-Square. In summarizing ‘‘What has been learnt,’’ Peters
as a model for the disease, and they found in the 1890s that states: ‘‘We may now take stock of the position. A purely in-
chickens developed polyneuritis when fed white rice, but that vitro research with brain tissue of the bird was started in the
rice bran acted as a preventive. Further studies in the 1920s first instance to improve the test for vitamin B-1 and later
at the Eijkman Institute in the Dutch West Indies elaborated extended to elucidate the enzyme with which the vitamin
some general characteristics of the necessary micronutrient in cooperated. It has not only helped to settle these problems
rice bran. The bird model was extended by R. A. Peters and his but it has proved the existence of pyruvate in normal metabolism.
colleagues, who used pigeons at Oxford University in England.
It has also shown that an in-vitro research upon brain
The connection of a role for the anti-beriberi factor in tissue which takes advantage of the in-vitro labours of biochemists,
carbohydrate metabolism became apparent with the report of
can be applied to in-vivo events. This is an imcarbohydrate
Japanese workers (Inawashiro and Hayasaka 1928) that lactic portant step in this field. It is further encouraging that the
acid disappeared more slowly from the blood of beriberi patients
work has led to the detection of pyruvate in the blood of
after exercise. Investigators at Oxford (Kinnersley and beriberi patients, which may well prove diagnostic. Surely
we
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