Vitamin в6: Pyridoxine, Pyridoxal and Pyridoxamine

Vitamin в : Pyridoxine, Pyridoxal and Pyridoxamine
6
T. U R B A Ń S K I , D.Sc.
Department of Chemistry, Institute of Technology, Warsaw-
V I T A M I N B , also known as pyridoxine, or adermin,
is a derivative of pyridine and in that respect is
similar to nicotinic acid and nicotinamide, which
also belong to the complex mixture originally called
vitamin в.
6
According to our present knowledge, vitamin в is
a group of three substances : an alcohol, pyridoxine,
an aldehyde, pyridoxal and an amine, pyridoxamine.
A l l three are derivatives of /У-hydroxypyridinc, and
thus there is a profound similarity between the
vitamin в
group and nicotinic acid and its
derivatives : in a l l of them the /^-position in the
pyridine ring is substituted by a group strongly
influencing the character of the molecule—the
phenolic group in vitamin в and the carboxylic
group in nicotinic acid.
6
0
In a series of p a p e r s
published in 1938
improved methods of isolating vitamin в
were
described.
Further
experiments
showed
that
vitamin B, is present in animal or vegetable tissue
in the form of a complex with proteins or carbo­
hydrates which is subject to cleavage by the action
of enzymes or heat. The richest sources of vitamin в
are yeast and rice bran. Various seeds including
corn also contain a considerable quantity, while
lesser amounts occur in molasses and liver. M i l k ,
egg yolk, spinach and green vegetables are poor
sources of vitamin в .
6-10
6
6
с
CHEMICAL PROPERTIES AND STRUCTURE
OF P Y R I D O X I N E
в
The
principal component
of vitamin B ,
pyridoxine, has the structure a-lnethyl-3-hydrOxy4.5-di(hydroxymethyl) pyridine, / .
C
The free base pyridoxine has the empirical formula
C H 0 N . It is a white crystalline substance with
m. pt i6o°C.
It is soluble i n water and most
organic solvents, and forms several salts e.g. the
hydrochloride (m. pt 204~2о6°С with decomposition).
R . K U H N and his co-workers
determined its
structure in an extremely skilful way within a very
short time. T h e main facts which led to their
conclusions were :
8
u
3
11
This was elucidated in 1939 by
experiments described below,
but the first mention of the
relationship
between
/)'-hydroxypyridinc and vitamin
в was given by R . R . WILLIAMS
i n 1921 i.e. long before vita­
min B was isolated.
CH.OH
HO
• \
CH.OH
41
CH,
1
E
few years later J . GOLDBEROER and R . D .
found certain types of dermatitis in rats fed
on diet free from vitamin в , (lactoflavin). T h e
dermatitis was produced by an unknown factor
present in vitamin в , since the rats d i d not recover
on administration of pure vitamin в .
A
LiLLiE-
2
г
/ The substance contains three hydroxyl groups,
but only one of them can be methylated with
diazomethane ; thus the substance has one phenolic
and two alcoholic groups.
s I f pyridoxine methylated with diazomethane
was subjected to heating with lead tetracetate, no
oxidation occurred. This indicates that the alcoholic
groups are not attached to the neighbouring carbon
atoms since lead tetracetate is a reagent which
oxidizes oc-glycols.
T h e n S. J . О Н П Л К Е isolated a new crystalline
substance from rice bran. H e found the cmpyrical
formula of the hydrochloride of this product to be
C Hj,0,N.HCl.
It was certainly pyridoxine,
although Ohdakc d i d not recognize the vitamin
character of the substance.
3 Pyridoxine methylated with diazomethane can
be oxidized with cold potassium permanganate.
One of the alcoholic groups is oxidized to a carboxylic
group which readily forms a lactone with the second
alcoholic group. As only y'- and sometimes (5-lactones
can be formed in this way, the alcoholic groups can
only occupy the 1.4 or 1.5 positions.
T h e name ' vitamin в ' appeared i n 1934,
bestowed by P. G Y O R G Y who isolated this substance
from yeast, rice bran and liver. H e found it to bc
an antipellagra factor, which can accompany
vitamin в in yeast, liver and other ' vitamin в '
sources.
T h e same author, together with T . W .
BlRCH , found vitamin B to bc a nitrogen base
which forms a hydrochloride.
4 The ultraviolet absorption spectrum shows a
great similarity between pyridoxine and /}-hydroxypyridine. Both pyridoxine and /5-hydroxypyridine
give a cherry red colour with ferric chloride, which
indicates the phenolic character of their hydroxyl
groups : a- and y-hydroxypyridine are not phenolic
in character and do not become coloured with ferric
chloride.
3
e
0
1
2
5
0
т.
2 -11
Research
URBAŃSKI:
Vitamin в : Pyridoxine, Pyridoxal and Pyridoxamine
6
8 K u h n and his co-workers synthesized a dibasic
acid Ilia.
It proved to be identical with the acid
formed from the methyl ether of pyridoxine, so
formula lb was therefore rejected.
5 If pyridoxine methylated with diazomethane
is oxidized with hot potassium permanganate in
alkaline medium a tribasic acid is formed which
gives a brown colour with ferrous sulphate. This
colour reaction is characteristic of pyridinic acids,
which contain a carboxylic group in a-position. O n
heating the acid looses a molecule of water and a
molecule of carbon dioxide, forming the anhydride
of a dibasic acid. T h e acid produced from this
anhydride does not give the colour reaction with
ferrous sulphate.
Independently the structure of pyridoxine was
also established by a team of workers i n the U . S . A .
Thus the acid Ilia was obtained - by oxidizing the
methyl ether of pyridoxine IV. This acid was
subsequently synthesized by a different method.
Both syntheses of the acid Ilia were important i n
providing a basis for the preparation of pyridoxine,
which both groups of investigators achieved shortly
afterwards.
1
13
These facts, together with the analytical data,
brought K u h n to the following conclusions :
a the three carboxyl groups are formed by the
oxidation o f two primary alcoholic a n d one
methyl group ;
b the carboxyl group, which is eliminated as C 0
on heating, occupies the a-position ;
SYNTHESIS OF PYRIDOXINE
14
2
с the two remaining carboxyl groups are attached
to the neighbouring carbons.
O n this basis
K u h n gives the structure of the anhydride / /
and three possible structures of pyridoxine,
la, lb and Ic :
CH..OH
HO,
/ N
CHJ
\CH,OH
4
Thus
the acid
CH.OH
CH.OH
CH
COOH
X
CH.O
3
(IV)
CH! J
N
(Ilia)
I
4
N
2
НО/^СКОН
CH
1
1
+
ВГ
H
В l'­
(V)
A n identical synthesis was also described by A .
ICHIBA and K . M i e n i .
1 5
The method of synthesizing pyridoxine developed
by S . Л . HARRIS and K . F O L K E R S gave the best
practical results from the viewpoints of yield a n d
cost o f production.
T h e y started from ethoxyacetylacetonc VI and cyanacetamide VII which
with piperidine in alcoholic solution underwent ring
closure and formed a pyridine derivative VIII :
10
CH.OC.H;
I
CO
COOH
сн,о I
CH OH
H,о
/
H
7 Careful oxidation of the methyl ether of.
pyridoxine with barium permanganate led to a
dibasic acid with an untouched methyl group. This
acid does not give any colour with ferrous sulphate.
It has therefore two possible structures, Ilia and 111b :•
:
3
(66%) C H , N .+!
(Ic)
COOH
сн о, ^ C K O H
CH I I
Ho/^CH.Br
2
COOH
CH.OH
CH.Br
HBr
6 K u h n and co-workers synthesized the anhydride
which possesses the structure / / . It proved to be
identical with that obtained from the methyl ether
of pyridoxine.
CH ,0
ether of
х
COOH
t JcH OH
N
the methyl
ix N
(IV)
(Ilia)
which was demcthylated to give the hydrobromidc :
но,/\сн.он
(lb)
gave
Ilia
pyridoxine IV :
(Щ
(la)
HO,
N
- C O O H - * - C O N H . -+ - C N - * - C H . N H , - * - C H . O H .
CH I
со—о
/
CHJOJ^NCO
NT
R . K u h n and his co-workers synthesized pyridoxine
by starting from the acid Ilia and transforming thé'
carboxyl groups according to the scheme :
COOH
CH,
CH.,
CH, -co
(Hlb)
Consequently the structure Ic for pyridoxine should
be rejected.
508
(VI)
+
CH.OCHj
piperidive
CN
CH —CN
2
yield 8,".
/
c=o
NH,
(VII)
=0
CH.,
NH
(VIII)
т. U R B A Ń S K I : Vitamin
в :
в
CH.,OC,H
J
NO.,,
(VIII)
yield 32%
CHJ
v
H
C N
Pyridoxine, Pyridoxal and Pyridoxamine
« >. N H ,
CN
(PT
уШвГ5
)=о
N
NH
COOCH
СН.ОСН-,
5
"'°сн1
)=o
NH
(IX)
J=o
CH
CH.
CH C,H
[XVII)
2
'
V '
O
2
6
с
yieldi6-5%
CH,I
N N
JCI
CH OC H,
5
2
CH OH
2
yUUjn-5% C H , I
(XI)
7
Recently A . C O H E N
proposed a new method
of preparing pyridoxine by starting from a-alanine
derivatives : N-benzyl-a-alaninc ester XIV and
a-hydroxymethylenesuccinic ester XV were cyclized
to a 3-kcto-i .2.3.4-tetrahydropyridine derivative
18
:
I
СН3--СН \
+
NH
COOCH
СООСН3
сн
ĆH,C,H,
(XIV)
2
\
CHJ
•
С.СООСН.,
HOĆH
(XV)
0=
CH.
I
t
J
HO^^CH.OH
yield 45-4°,'oCV\
(la)
20
developed . Experiments on the growth of bacteria
on a medium containing pyridoxine led to some
important conclusions. E . E . SNELL, В. M . GUIRARD
and R . J . W I L L I A M S
found that Strep lactis R
would grow on such a medium many times faster
than could be accounted for on the basis of actual
pyridoxine content.
T h e explanation is that
pyridoxine was converted into a more highly active
metabolite prior to utilization by the bacterial
organism. This hypothetical metabolite was called
pseudopyridoxine.
21
In his later experiments E . E . S N E L L found that
media containing pyridoxine could be activated by
simple heating in an autoclave. H e advanced a
suggestion that pseudopyridoxine was formed by
the interaction of pyridoxine and aminoacids present
in the mixtures. H e developed his experiments
further and heated pyridoxine a with ammonia i n
an autoclave b with manganese dioxide.
2 2
23
3
соосн.,
CHX H
(XVI)
4 | 4
HOMO
(XIII)
17
СООС..Н,
âNH/^CHjNHjCI
(XII)
This was reduced by hydrogen on platinum and
palladium with the simultaneous removal of chlorine,
giving the amine XII. Hydrolysis with hydrochloric
acid at i 7 5 - i 8 o ° C yielded the aminoalcohol XIII
which on diazotization finally gave pyridoxine. A n
almost identical method was adopted by Merck A . G .
in Germany for the commercial synthesis of
pyridoxine .
XVI
HCI
yield (sy)>„
N K
СН..ОН
2
NH/NCH.NH,,
t
R.
PYRIDOXAL AND PYRIDOXAMINE
(PSEUDOPYRIDOXINE)
It was found in 1938-39 that vitamin в is a growthpromoting agent for yeast and bacteria. A biological
method for the assay of pyridoxine was then
H
H,(p -Pd)
(XVIII)
1 9
Thus product X can be transformed into A ' / :
СН ОС,Н
5
3
a-hydroxypyridine
PCI. + POCI, N H j / N c N
N
T h e product XVIII can be converted into pyridoxine
in the conventional way by stepwise transformation of
- C O O C H into - C H j O H . This synthesis suggested
the possible functioning of a-alanine as a natural
precursor of pyridoxine and it is interesting to note
that E . E . S N E L L found alanine capable of replacing
vitamin в for the growth of Lactobacillus casei and
N
a-pyridone
2 -11
3
HOf^NcoocH,
(A')
<
COOCH
HO/NCOOCH,
Streptococcus faecalis
NH
3
I
Substance VIII was nitrated to IX and then reduced
by platinum black to the amine X. Substance X,
which is an a-pyridone derivative, can be transformed
by phosphorus pcntachloridc and phosphorus oxychloridc into an oc-chloropyridinc derivative, because
a-pyridone reacts tautomerically as a-hydroxypyridine :
{
Research
5
T h e product was dehydrogenated to XVII and after
hydrogenolysis of the N-benzyl group the substance
XVIII was obtained.
509
In both instances he obtained products much
more active than pyridoxine. In the experiments a
they were 140 times more active than pyridoxine,
and in b 50 times. H e therefore suggested that
animation and partial oxidation are possible reactions
which can transform pyridoxine into pseudo­
pyridoxine. Pseudopyridoxine is therefore a mixture
Research 2 - 1 1
т. U R B A Ń S K I : V i t a m i n в
of two substances, the product of oxidation, which
Snell called pyridoxal, and the product of amination,
which he called pyridoxamine.
T h e following
reaction scheme represents this transformation :
[O]
R.CH OH
NH
5t
NH
R . C H O <lt R . C H
2
Ptridoxine
The product possessed the properties of pyridoxamine,
as determined from its action o n the growth o f
Lact casei and Strep lactis R .
Harris, H e y l and Folkers also prepared pyridoxal
XXVaXià transformed it into pyridoxamine, providing
evidence that the same 4-hydroxymcthyl group was
transformed into an aldehyde and methylamino
group respectively. Pyridoxal was prepared by a
careful oxidation of pyridoxine in an alkaline medium :
[H]
:i
R.CH.NH.,
Pyridoxamine
Pyridoxal
Snell's metabolic experiments with rats and human
beings also led to the conclusion that pyridoxine is
partially converted by animal organisms into
pseudopyridoxinc.
CH.NH,
но/Чсн..он
CH
N '
(XIX)
: Pyridoxine, Pyridoxal and Pyridoxamine
6
25
ĆH,OH
NH /\cH,NH..
2
C H
:i4
J
N
[Xlla)
CH..OH
HO
KMnO,
Independently R . K U H N found
that patients cured with pyridoxine
excreted i n their urine a new
substance much more potent than
pyridoxine, which possesses the
structure XIX.
!1
CH
~^CH,
:L
NH..OH
N
(XXV)
CH.NH.
CH = NOH
HO/NCH.,OH
сн
No details were given of how he arrived at this
conclusion.
The structures
were established
K . FOLKERS
by
and their isomers.
the methyl ether
CHO
CH,OH
HO/NCH.OH
з ч
[H]
НО/
CH
J
of pyridoxal and pyridoxamine
by S. A . HARRIS, D . H E Y L a n d
synthesizing these two products
T h e y started from substance XX,
of the alcohol Xlla.
homologous
with substance XII, the ethyl
ether
of the same
alcohol.
Diazotization of XX gave the
product XXI.
O n action of
thionyl chloride the alcoholic
group was replaced by chlorine
I I
TN
(XXVI)
>СН,ОН
N
(XIX)
T h e aldehyde XXV was transformed into the oxime
and this was catalytically reduced to pyridoxamine.
F i n a l confirmation of the struc­
ture
of pyridoxal was obtained
HO
,CHO
when the same authors synthesized
the isomeric aldehyde
CH,
XXVII,
N
which does not possess the growth
{XXVII)
promoting activity of pyridoxal.
Further, E . E. S N E L L found that all three members
of the vitamin в group occur i n natural tissues. I n
various papers E . E . SNELL and his co-worker
showed that the three compounds pyridoxine,
pyridoxal and pyridoxamine each behave very
differently towards different organisms.
СН..ОН
4
2 0
0
which was then substituted by the amino group
; finally the ether group was hydrolyscd with
hydrochloric acid at i 7 0 - i 8 o ° C and product
XXIV
was obtained.
There was no doubt about the
structure of this compound, which on bio-assay
proved to be non-identical with pyridoxamine and
did not possess its activity.
27
XXII
XXIII
CH,OCH
NH
2
СН.ОСК,
; 1
CH..NH,
CH OCH
2
но/^сн-рн
(XX)
HO
CH,
(XXI)
N'
(XXII)
Acting on substance XXI with ammonia at 140°C
in methyl alcohol, they obtained the substance XIX
identical with pyridoxamine :
CH,OCH
CH
N
(XXI)
CH.NH,
; 1
HÓ/\CH,OH
HO
/ X
jCH.OH
CH,
(XIX)
СН..ОН
СН..ОСН,
: l
СН..С1
SOCI
з\|ч| J
СН
CH
Thus they found pyridoxal has 5,000-8,000 times
and pyridoxamine 6,000-9,000 times the activity of
HO
CHJ
H O ^ C H . N H ,
'NcH-.NH,
V N
(XXIII i
{170-180")
(+ 2НС1)
CH
(XXIV)
pyridoxine as a growth factor for Strep lactis R . F o r
other organisms, such as Lact casei, pyridoxal was
also found to be highly active, but pyridoxine and
pyridoxamine almost inactive. O n the contrary,
for Saccharomyces carlsbcrgensis all the compounds have
approximately equal activities. It is assumed that
the variation i n activity is due to differences i n the
ease with which the various organisms convert
pyridoxine into pyridoxamine and pyridoxal.
т. U R B A Ń S K I :
Vitamin
в
с
:
Pyridoxine, Pyridoxal and
The original presence or formation of the members
of vitamin в„ groups renders microbiological assay
for vitamin B invalid if the growth of unsuitable
organisms is examined.
For that reason it is
preferable to use organisms which respond equally to
all three members of the group e.g. Sacch carlsbergcnsis
and Neurosppra sitophila.
g
P H Y S I O L O G I C A L A C T I O N OF V I T A M I N B
E
33
3 4
с
35
29
30
More recently a relation between the vitamin в
deficiency and anaemia has been clearly shown by
several authors. S. L E P K O V S K Y found that anaemia
produced by the lack of pyridoxine does not respond
to iron and copper, but prompt improvement
follows
administration of pyridoxine.
M. M.
WINTROBF. et alii
showed that pigs fed on a diet
supplemented with vitamins A and D and all known
vitamins в except B develop a severe microcytic
anaemia frequently accompanied by epileptic con­
vulsions. Administration of pyridoxine produced
rapid regeneration of blood.
0
30
31
E
It is known that kynurenine, an amino acid, and
xanthurenic acid, a quinoline derivative, can be
excreted by animals suffering from nutritional
disorders. It has also been shown that both sub­
stances are products of incomplete metabolism of
tryptophane. S. LEPKOVSKY et alii - established the
exact dietary deficiency necessary to produce the
excretion of xanfhurenic acid. They found that
I
COOH
CH,
HO|
CH
CH.OH
protein
1
V
C=
1
J
N '
fyndoxamine-protein
complex
A further discovery was the function of pyridoxine
derivatives as agents playing important parts i n
biological transaminations. Previously E . E . S N E L L
had suggested that the possible conversion of pyridoxal
into pyridoxamine may be explained by a trans­
amination reaction.
In a number of papers he
showed that a relation existed between members of
vitamin B group and the process of transamination.
T h e n H . C . LICHSTEIN, I. C . GUNSALUS and W . W .
U M B R E I T found that pyridoxal phosphate functioned
as the coenzyme of the transaminase of certain acids.
3 7
E
33
The process of transamination shown below was
suggested by F. SCHLENK and A . F I S C H E R .
39
Another function of pyridoxal phosphate was
found by W . W . UMBREIT, W . A . WOOD and I. C .
GUNSALUS . T h e y proved it to be the coenzyme
40
R
+ N H ,
I
The discovery that vitamin B is closely related to
certain enzymes was the most important part of
the research on its biological action. The first
observation was related to the role of vitamin в
in the transformation of certain amino acids to
amines i.e. of their decarboxylation by decarboxylase.
Thus W . D . B E L L A M Y and I. C . G U N S A L U S found
that addition of pyridoxine and nicotinic acid or
pyridoxal stimulated production of tyrosine decar­
boxylase.
T h e n J . BADDILEY and E . F. G A L E
and, almost simultaneously, W . W . UMBREIT and
I. C . GUNSALUS discovered that phosphorylated
pyridoxal can act as co-decarboxylase. In addition,
others
prepared phosphorylated pyridoxal with
40 to 5 0 per cent coenzyme activity from pyridoxal
and phosphorus oxychloride. T h e exact position
of the phosphoric acid group i n this coenzyme is
not yet known.
6
2
CO
pyridoxine deficient rats excreted in their urine a
complex of xanthurenic acid and iron.
This
excretion of iron might be one of the factors causing
anaemia. O n the basis of this and some later work
the role of pyridoxine was established as a factor
producing metabolism of tryptophane and par­
ticularly of kynurenine and xanthurenic acid. This
property of pyridoxine was later elucidated in the
course of work on the coenzyme action of phosphorylated pyridoxal quoted below.
g
6
3
Research 2 — 11
40
6
None of the members of the vitamin B group
produces a definite pharmacological action and this
is the main reason why the part played by this
vitamin was obscure.
T h e earliest experiments
showed a connection between vitamin в and certain
skin disorders, so typical for most в group vitamins.
This was confirmed by later experiments. A special
type of dermatitis, acrodinia, occurring on peripheral
parts of the bodies of animals is due to lack of
vitamin в . It was also suggested that vitamin в
is an agent in the metabolism of unsaturated fatty
acids ". Experiments with rats gave evidence of
the importance of pyridoxine i n the process of
transformation of proteins into fats .
6
Pyridoxamine
HOOC
I
N
CH.,
!
HO,
C H — N H . , -|- C H O
CH—N
II
HOOC
I
CH
HOOC
H<Y
CH..OH
НО?
X
|CH,OH
ru
(CH.OH
\protein
•'^ N ^
pyridoxal-protein
complex
Research 2 - 11
j.
L C
for tryptophanase which catalyses the breakdown
of tryptophane to indole, pyruvic acid and ammonia.
1 8
6
2
2
3
4
REFERENCES
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OHDAKE, S. J . Bull. agr. chem. Soc. Japan
2 0
5
7
2 1
2 2
2 3
2 ł
2 6
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2 8
2 9
3 0
" K U H N , R. and WENDT, G .
1118, 1534
—
—
ibid
1 1
—
ibid
1 1
ANDERSAG, H., WESTPHAL, K . and WENDT, G .
— WENDT,, G . and WESTPHAL, К .
ibid
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—
—
ibid
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157 (1945) 491
ibid
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Bull.
64 (1939) 399
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153 (1944) 171
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149 (194З) "95
1 1
Tokyo
155 (1944)
2
99
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(1944) 191
J. Bad.
—
—
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(1945) 727
3 5
3 7
UMBREIT, W. W . and
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J.
159 (1945) 333
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Amer. chem. Soc. 1946 35 в
SNELL, E . E . J. biol. Chem.
48
155
biol. Chem.
iwtli Meet.
154 (1944) 313
3 8
LICHSTEIN, H . C , GUNSALUS, L C , UMBREIT, W. \ V .
3 9
SCHI.ENK, F. and FISCHER, A . Arch. Biol. 12 (1947) 69
UMBREIT, W . W . , WOOD, W . A . and GUNSALUS, I. C .
ibid
Inst. phys. chem. Res.,
J. Amer,
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BIRCH, T . W . ibid 124 (1938) 775
MCHENRY, E . W . and GAVIN, G . ibid 138(1941)471
LEPKOVSKY, S. ibid 149 (194З) ' 9 5
ibid
3 3
27 (1939) 469
ICHIBA, A . and Mieni, K .
35 (1938) 73
Ind. Eng. Chem.
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—
Proc. Soc. exper. biol. Med.
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—
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C.I.O.S. Report XXIV—13
ibid
3 6
HARRIS, S. A . , STILLER, E. J . and FOLKERS, K . ibid Gi
(1939) 1242
KUHN, R., WESTPHAL, К., WENDT, G . and WESTPHAL,О.
.Xaturwiss.
1 0
71 (1938) 780,
72 (1939) 309
61 (1939)
158 (1945) 497
J. biol. Chem.
REID, D. F., LEPKOVSKY, S., BONNER, D. and TATUM, E. L .
72 (1939) 305
J. Amer. chem. Soc.
1:1
Ber.
1947
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PHREYS, S.
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SNELL, E . E .
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— FOLLIS, R. H., MILLER, M . H., STEIN, H . J.,
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CARTWRIGHT, G . E . , WINTROBE, M . M . and HUM­
34 (1938) 623
GYORGY, P.
61
ATKIN, L . , SCHULTZ, A . S. and FREY, G . N . J. Amer,
John, Hopkins Hosp.
8
1 0
B.I.O.S. Report Mo. 766, 159
COHEN, A .
Xlth intern. Congr.
—
3 1
6
KERESZTESY, J . C . and STEVENS, J . R.
Proc. Soc. exper.
biol. Med.
38(1938)64
* ICHIBA, Л. and MICHI, K .
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—
—
—
and WILLIAMS, W . L .
Anal.
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GYÔRGY, P. Nature, Land. 133 (1934) 498
— Biochem. J. 29 (1935) 7 4 . 7 °> 7»7
BIRCH, T . W . and GYÓRGY, P. ibid 30 (1936) 304
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LEPKOVSKY, S. Science 87(1938) 169
1
6
8 (1932) 111
HARRIS, S. A . and FOLKERS, K .
Abstr. 247/3
1 0
2 0
1
Inflammability of Gases
(>939) 1245. ЗЗ07
1 7
The complex behaviour of the vitamin в group
gives no clear indication of its use in therapy. They
may be useful remedies against some types of
anaemia and some skin disorders, including such
symptoms of pellagra which arc not relieved by the
usual treatment with vitamin в , , в and nicotinic
acid. It is certain that pyridoxine is an invaluable
remedy against certain nervous disorders accom­
panied by insomnia and irritability, and also against
vomiting in pregnancy. It is of value i n treating
muscular dystrophy, paralysis agitans and chorea.
п. B U R G O Y N E :
411
36 (1939) i , 173
161 (1945) 311'
J. biol. Chem. 165 (1946) 731
—
—
—
ibid "169 (1947) 631
Inflammability of Gases
J. H . B U R G O Y N E ,
D.Sc, F.R.I.C.
Imperial College of Science and Technology, London
LIMITS OF I N F L A M M A B I L I T Y A T
ATMOSPHERIC TEMPERATURE
I T has long been known that gases capable of flame
propagation in air can only be inflamed between
certain limits of concentration.
A moment's
rcllection shows the theoretical necessity of such
limits. Thus, while a mixture containing the fuel gas
and oxygen i n stoichiometric proportions may be
expected to propagate flame mere readily than others
because it has a m a x i m u m calorific value, dilution
with either constituent may be expected to reduce
the calorific value such that eventually the tern-