вход по аккаунту


Biochemistry of the Pteridines.

код для вставкиСкачать
2931 S. Z . Roginskii, A . A. Berlin, D. A. Galovina, E . S . Dokukina, M . M .
Sakharoo, and L. G. Cherkashina, Kinet. Katal. 4,431 (1963).
[94] W Hanke, Z . Anorg. Allg. Chem. 347,67 (1966).
[95] W Hanke and W Karsch, Monatsber. Deut. Akad. Wiss. Berlin 9,
323 (1967).
[96] H.Inoue, S. Hayashi, and E. Imoto, Bull. Chem. SOC.Jap. 37, 326
[97] R. Jasinski, Nature 201, 1212 (1964); J. Elektrochem. SOC.112,
526 (1965).
[98] R. Jasinski, US-Pat. 3410727, November 12,1968.
1991 Siemens AG, French Pat. 1591 825 (1970).
[loo] H. Jahnke, Ber. Bunsenges. Phys. Chem. 72,1053 (1968).
[loll R. Bosch GmbH, French Pat. 1538821 (1967).
[lo21 H. Jahnke and M . Schonborn, Proc. Joint Int. Etud. Piles Combust. Brussels 1969, p. 60.
[lo31 H. Jahnke, Report on 3. Int. Farbensymposium Lindau 1970,
p. 86.
[lo41 M . Schaldach, Umschau 70,857 (1970).
Biochemistry of the Pteridines
By Heinz Rembold and William L. Gyurer*]
Biochemical information about the ubiquitous pteridines has become generally available
only within the last fifteen years. This delay can be traced to the chemical lability of these
compounds and their small concentrations in organisms. New methods of isolation and
isotopic techniques have provided data on the biosynthesis, anabolism, and catabolism of
this class of compounds. Hydrogenated pteridines are recognized today as cofactors for
various mixed function oxygenases and are involved in cellular electron transport. Further
unknown catalytic functions for pteridines in cellular metabolism are indicated by their
physiological activity, negative redox potentials, and histoautoradiographic data.
1. Introduction
At the end of the last century Hopkins reported on a
crystalline pigment which he had extracted from the wings
of a butterfly“’. This finding formed the basis for later
investigationsby Wielandand hisco-workerswho succeeded
in isolating first a yellow121and then a white pigment”’.
After much experimental difficulty Purrmunn was finally
able in 1940 to determine the structure of these natural
pigments, which were named xanthopterin (35) and
leucopterin (37). At the same time he also elucidated the
structure of a related pigment called isoxanthopterin
For the bicyclic ring system of these new butterfly pigments
Wielund chose the name “pteridine” while the designation
“pterin” was originally used as a general term for all insect
pigments. Today pyrazino[2,3-d] pyrimidine is called
pteridine (2). The naturally occurring pteridines are
commonly called pterins when they are derivatives of the
parent compound 2-amino-4-oxodihydropteridine( 3 ) and
lumazines when they are derivatives of 2,4-dioxotetrahydropteridine ( 4 ) .
As a simple approach pteridines (2) may be considered
related to the purines ( I ) to which they bear a structural
resemblance. Both classes of compounds have many
[*] Prof. Dr. H. Rembold and Dr. W. L. Gyure
(American Cancer Society Postdoctoral Fellow)“”
Max-Planck-Institut fur Biochemie
8033 Martinsried bei Miinchen (Germany)
[**I Present address:
University Hospital BB-203
University of Washington
Seattle, Washington 98105 (USA)
Angew. Chem. internat. Edit. / Vol. I1 (1972) / No. I 2
properties in common such as low solubility at neutral pH
values, well defined ultraviolet absorption spectra, ability
to form chelates with metal ions, and the property of
forming precipitates with mercury and silver salts. In
addition to the purine-like properties, fully oxidized, or
aromatic, pteridines exhibit strong blue to red fluorescence when irradiated with ultraviolet light. This fact aids
their purification from sources containing only trace
amounts of these compounds.
Reviews of the chemistry of the pteridines are availablec5.‘I.
One property of pteridines is especially important from
a biochemical standpoint and that is their ability to form
dihydro and tetrahydro derivatives. These reduced forms
are very reactive and not only can they serve as specific
reductants but they can also participate in electron transport reactions. It is precisely because these reduced forms
are so reactive that working with them is difficult. The
aromatic structures are already photolabile while the
reduced forms are even more photolabile and subject to
oxidative degradations. As an example of this lability,
reduced biopterin and neopterin can respectively lose their
dihydroxypropyl and trihydroxypropyl side chains simply
upon heating in neutral aqueous solution in the presence
of airl71.
2. Isolation
The naturally occurring pteridines are found throughout
the plant and animal kingdoms. Several reviews discuss the
pteridines found especially in insects[*l, in microbes[g1,and
in amphibia and fish'"]. Normally pteridines are found in
only trace amounts in biological material. Biopterin (6b)
occurs, for example, in concentrations of less than 10mg/kg
and other pteridines are often present in even lower
amounts. In Table 1 the results of an analysis of honeybees
clearly illustrates this general fact.
use depends upon the solubility and lability ofthe pteridine
in question (Table 2). Relatively soluble pteridines such as
the 6-polyhydroxyalkyl derivatives [biopterin (6b), neopterin (6a), sepiapterin (7b), etc.] can be isolated from
trichloroacetic .acid extracts. These extracts are free of
most protein and peptide materials and labile hydrogenated
pteridines are stabilized under the acidic conditions. Acid
extraction however cannot beused ina quantitative sense for
such acid-insoluble pteridines and lumazines as isoxanthopterin, leucopterin, and 7-hydroxylumazine. Often pteridines occur in association with other molecules such as
protein, peptides, and nucleic acids[13, 14]. In order to
isolate these complexed pteridines and to solubilize the
acid-insoluble pteridines, basic solvents are useful and
when used in conjunction with an alkaline precipitation
Pierid butterflies, utilized in Wieland's original studies,
contain relatively high concentrations of pterins. Along
with other compounds, xanthopterin (35),isoxanthopterin
(38), and leucopterin (37) serve these insects as pigments.
However, disregarding a few exceptions among fish and
amphibians, pteridines generally occur in very small
concentrations. Examination of the values in Table 1 shows
that many pteridines must be enriched 10' fold in order to
reach an analytically pure state.
C H O H - C H O H - CHzOH
A variety of methods are available for the isolation of these
compounds from natural sources; the choice of which to
Table 1. The pteridines listed as occurring in the honeybee [ll, 127, Apis
meNifca L., are given in micrograms per animal. The average weight of a
bee is 150-200 mg.
Flight bee
Biopterin (6 6 )
Neopterin (6a)
7-Hydroxylumazine (30)
Isoxanthopterin (38)
Pterin (3)
6-Pterincarboxylic acid
Table 2. Procedures for isolating and identifying pteridines from biological material.
1. Extraction
Type of pteridine
Extraction medium
Protein and peptide removal
acid-soluble pteridines
alkaline-soluble pteridines
labile reduced pteridines
water or 5% trichloroacetic acid
water or 5% trichloroacetic acid
trichloroacetic acid 1171
trichloroacetic acid [IS]
or sephadex 1191
NH,OH with mercaptoethanol
2. Purification
Column chromatography (Dowex 1 and 50 1177, phosphocellulose [17], ecteola cellulose 1171, cellulose [20],
Florisil 191); paper chromatography 1211; thin layer chromatography 1221 ; paper electrophoresis [23] ;electrophoresis on cellulose acetate 1241;isoelectric focusing [25]
3. Identification
UV absorption spectra; fluorescence emission spectra; chromatographic behavior; Criihidia growth tests [26];
color tests [l5, 271; enzyme tests [28]; gas chromatography [29, 301
4. Quantitative determinations
UV extinction coefficient; measurement of fluorescence on paper 1311 or in solution [32] ; Crithidia growth 1261;
isotopic dilution [I 81 ; color tests 115, 271; enzyme tests 1281 ; gas chromatography [29,30]
Angew. Chem. internat. Edit. 1 Vol. 11 (1972) / N o . 12
method give quantitative results['51. Alkaline extraction
methods necessitate precautions, such as the addition of
mercaptoethanol to the solvent, to prevent the degradation
of the labile reduced pteridines.
Depending on the conditions used the structure of the
reduced pteridines can be changed during isolation. As an
example, tetrahydroneopterin ( 5 ) can be adsorbed on a
column of phosphocellulose and eluted with dilute formic
acid in the presence of mercaptoethanol. After evaporation,
renewed chromatography of the eluate on the same
column yields two bands upon elution with water. Structural
showed that tetrahydroneopterin is oxidized in the process producing neopterin (6a) and a yellow
pterin 6-(3-hydroxypropionyl)-7,8-dihydropterin (7a).
When the original tetrahydroneopterin is chromatographed
in the absence of mercaptoethanol, the dihydropterin is
formed o n the column.
Once the pteridines have been extracted, they can be
purified, identified, and assayed by the methods in Table 2.
Nuclear magnetic resonance, mass spectroscopy, and
elemental analysis are additional methods which aid in
identification; however they are of limited value due to the
low solubility and volatility of most pteridines. After preparation of trimethylsilyl derivatives even very polar
pteridines are volatile enough to be separated by gas
chromatography and identified by mass spectral fragmentati~n'~'.301.
however cautions against accepting the Brown-Shiota
pathway as the sole mode of pteridine synthesis. A cyclic
dihydroneopterin phosphate has been found by Cone and
G u v o ~ J I ' *to
~ ' be the end product of GTP conversion in
Cornamonas. In addition Forrest191rightly discusses the
possibility of alternate pathways for pteridine biosynthesis,
such as from a pyrazine compound. Another possibility
has been put forward by T ~ k e d ain~ his
~ ~studies
on the
formation of indolyl- and hydroxyphenylpteridines by
Achromobacter petrophilum. Although GTP ( 8 ) and
xanthine derivatives (13) were utilized by the microbe for
the formation of the pteridines, radioactivity was incorporated into the ring system when [3-'4C]tryptophan was
added to the culture medium. Takeda discusses the
following biosynthetic route to (17)r'] :
0" 'OH
0" 'OH
3. Metabolism
3.1. Biosynthesis of the Reridine Ring
Because of structural similarities purines and pyrimidines
were early considered as potential starting materials for
pteridine biosynthesis. Numerous studies indicated that
purines are utilized for pteridine ring formation in bacteria,
fungi, amphibia, and insects[33'. Direct proof of this conversion has been offered by Brown et al.r34]who have
isolated the enzyme GTP-cyclohydrolase from Escherichia
coli. This enzyme catalyzes the conversion of guanosine5'-triphosphate ( 8 ) into ~-erythro-7,8-dihydroneopterin3'-triphosphate (12). Shiota has isolated a similar enzyme
from Lactobacillus plantarum.
Many reports tend to support this set of reactions and these
[ ~ by
~ ~Brownr341in their
have been discussed by S h i ~ t aand
reviews on the biosynthesis of folic acid. Recent data
Angew. Chem. internat. Edit. j Vol. I 1 (1972) / N o . I 2
Data on pterin biosynthesis in the rat is also difficult to
resolve utilizing the Brown-Shiota scheme. In studies on
possible precursors in the rat, Remboldetal. haveestablished
that biopterin excretion per day is constant at about 30 pg
even when several generations are fed on a biopterin free
dietr3']. This indicates biopterin formation in a mammal
which is incapable of forming folic acid. When purine precursors, such as formate and glycine, or possible pteridine
[*I Note added in Proof (October 12, 1972): 6-(3-Indolyl)-7-oxo-8(1-D-ribity1)lumazine (17) has also been isolated from a culture of
pseudomonas o t ; a l i s ~ ~This
fact shows that
scheme of
pteridine biosynthesis may also occur in Pseudomonas.
precursors, such as adenine, guanine, guanosine, guanylic
acid, or GTP, were injected or fed to rats only trace amounts
were converted to biopterin. The formation of biopterin
was somewhat increased when nucleic acid synthesis was
inhibited by injection of actinomycin D and the accompanying flow of purine precursors into nucleic acid biosynthesis was decrea~ed~~’].
The injection of radioactive
neopterin (6a) or radioactive tetrahydroneopterin (5) did
not result in incorporation of label into the biopterin
excreted over the next four days[381.Fuk~shirna[~~]
described a very low incorporation of radioactivity into
biopterin by tadpoles of Ram catesbeiuna after injection
of dihydroneopterin or its triphosphate derivative. These
results in the rat and tadpole make it difficult to postulate
the involvement of neopterin or one of its derivatives as an
intermediate in biopterin synthesis.
3.2. Anabolism
Once the pteridine ring has been formed by an organism a
considerable number of subsequent reactions must occur
in order to account for the great diversity of naturally
occurring pteridines. The first results in the clarification
of the metabolic steps are now beginning to appear. Table 3
is a summary of the investigated enzymes and their
In spite of the great effort expended the direct relationship
between neopterin (6a) and the other pteridines found in
nature is not yet clear, the intermediates in folic acid biosynthesis being excluded. This is remarkable since neopterin is the parent and first pteridine formed according to
the Brown-Shiota scheme. The unknown relation between
neopterin and biopterin (6 b) has already been mentioned.
In this connection recent work by Dayman and Gurofllll]
has shown the presence of a neopterin cyclic phosphate
phosphodiesterase in E. coli, in Cornamonas, and in the
rat. This enzyme catalyzes the hydrolysis of neopterin
cyclic phosphate to neopterin phosphate. Gurofl’OZ1
suggests that in this hydrolysis the neopterin side chain is
inverted from the D-erythro to the L-threo configuration.
Such a coupled reaction, i. e. hydrolysis and inversion, can
explain why neither D-erythro-neopterin nor its noncyclic phosphate derivative can be converted to biopterin.
Even more fundamental and still debated is the origin of the
carbon chain on C-6 of the pteridine ring. Three hypotheses have been advanced concerning the chain[33].The
first one states that it is formed by a simple rearrangement
of the intact neopterin side chain in which the hydroxyl
groups are enzymatically epimerized. This hypothesis is
the basis for Guroffs suggestion as described above. This
statement assumes that 7,8-dihydroneopterin (18), or one
of its phosphate derivatives, is the parent compound for
the whole series of 6-(polyhydroxyalkyl)pteridines, including biopterin. The second hypothesis states that 6substituted pteridines arise by an addition of carbon units
to a 6-methylpteridine (20). This statement assumes nothing about the origin of the 6-methylpteridine nor of
the carbon units attached to it. According to the third
hypothesis carbon units are attached directly to the
pteridine ring (2I)-in the case of biopterin a three-carbon
unit is attached. These three suggestions are illustrated for
the formation of 7,8-dihydrobiopterin (19).
From the available data there is much that could be said
for and against each hypothesis and it may well be that
each plays its own role depending on the particular
Table 3. Summary of enzymes involved in pteridine metabolism.
Type of reaction
Enzyme (source)
GTP cyclohydrolase [41,102]
(E. coli, Cornamonas sp.)
triphosphate and
cyclic phosphate
synthetase [48] ( L . plantarum)
dihydroneopterinaldolase [49]
( E . coli)
pyrophosphorylase[SO, 511
(E. coli, L . plantarum)
dihydropteroatesynthetase [521
(pea seedlings)
( E . coIi[SO], L.plantarum [Sl],
pea seylings [S21)
erythropterin synthetase [32]
(Oncopeltus fasciatus)
biopterin and
sepiapterin synthesis
sepiapterin reductase [54,98]
(rat liver, horse liver)
dihydrofolatereductase [I081
dihydropterin reductase [73,114]
(sheep liver, rat liver)
reduced sepiapterin, tetrabydrobiopterin
neopterincyclic phosphate
neopterin cyclic
folic acid
neopterin synthesis
Angew. Chem. internat. Edit.1 Vol. I 1 (1972) 1 No. 12
veniently the erythro and threo isomers can be chromatographically separated from one another, while further
determination of an unknown isomer by the Crithidiu test
is only applicable to the eryfhro series. In the case of the
threo series optical rotations must be measured, a necessity
not always met for the natural threo isomers listed in the
literature. Because of the similarities of the isomers, all
four optical forms should be tested for their cofactor
activity in enzymatic reactions.
VH $)H
X = -H, -OH, -C@,
According to the Brown-Shiota scheme D-erythro-neopterin is the parent compound formed in E. ~ o l h ~ ~ . ~ ~ ] .
L-threo-Neopterin is however found in various organisms
The direct addition of a complete carbon chain to position
and indeed it is the chief pteridine found in E. coli itself'421.
7 of the pteridine ring is illustrated by the synthesis of
Brown[431has reported on neopterin epimerase activity
erythropterin. In the butterflies Colius eurytheme and
found in this bacterium. His preliminary results, which
Colius croceus xanthopterin (35) and, even better,
ought to be further tested, indicate an alteration of the
dihydroxanthopterin (26) are directly incorporated into
optical configuration of the intact dihydroneopterin side
erythropterin (28)[462471. With xanthopterin as a cosubchain.
strate, Forrest'32' found that in the eggs of Oncopeltus
oxaloacetic acid (27) is utilized for the formation
of the erythropterin side chain.
R ~ ~ C H , O H
3.3. Catabolism
L-erythro (24)
The degradation of pteridines is now better understood
than any other part of their biochemistry. In a series of
studies Rembold et ul. have shown that tetrahydrobiopterin
L-threo (25)
This scheme is based on the assumption of the validity of
the first hypothesis on the origin of the side chain.
The characteristics of the four optical isomers of neopterin'441and of b i ~ p t e r i n ' ~are
~ ]listed in Table 4.ConTable 4.Characteristics of the four optical isomers of neopterin 1441 and
biopterin 1451. R , values measured in isopropanol/5 "/, boric acid solution (4:l).
R , values
Neopterin (6 a )
L -eryfhro
Biopterin (6 b)
half optimal
growth concentration
(nglml medium)
Angew. Chem. internat. Edit. / Vol. I1 (1972)1 No. 12
+ 61
- 94
+ 95
_- (34)
P D = pterin deaminase
Xo =
xanthine oxidase
(42) and tetrahydroneopterin (22) are degraded similarly
in uitro by rat liver homogenates and in viuo after intraperitoneal injection into the ratE7.s5, 561. The main
pathway leading to the formation of simple lumazines is
shown in the formula scheme.
After the polyhydroxyalkyl chain is oxidatively cleaved in
a non-enzymatic reaction to form an aldehyde, the
remaining 7,8-dihydropterin (29) is used as a substrate in
either of two enzyme-catalyzed reactions. The pterin can
be oxidized to dihydroxanthopterin (26) by xanthine
~xidase["~or it can serve as a substrate for the highly
specific enzyme pterin deaminase. In the last case, which
is illustrated in the above scheme, either 7,8-dihydrolumazine (31) or lumazine (4) is formed, depending on the state
of oxidation ofthe substrate of the deaminase. The products
in both cases serve as further substrates for xanthine
oxidase and the end result is the formation of either
6,7-dihydroxylumazine (34) or 7-hydroxylumazine (30).
Levy and M c N ~ t t [ '591
~ , examined the degradation of
pteridines by the organism Alcaligenes faecalis and found
that starting with the simple pteridines isoxanthopterin
(38) and xanthopterin (3s) a series of deaminations and
oxidations yielded the same lumazine derivatives as noted
in the studies conducted with rats. However, Alcaligenes
was able to proceed one step further and convert the
6,7-dihydroxylumazine (34) into its isomer xanthine8-carboxylic acid (36), i.e. the pteridine ring was converted into a purine ring.
at different oxygen partial pressures and showed that
reducing conditions favored the formation of xanthopterin (35) and other 6-substituted pterins in the adult
while high oxygen partial pressure favored the formation
of pterins oxidized at position 7. D ~ s t m a n n ' ~found
6-hydroxylumazine (33) and 6,7-dihydroxylumazine (34)
in drone honeybees while Rembold and Buschmann['21
t et r ahydr one opt e r in
tetrahydro- 6 hydroxymethylpterin
XO = xanthine oxidase
found that worker bees accumulated 7-hydroxylumazine
(see Table 1). Drone honeybees apparently utilize 7,8dihydrolumazine while worker bees use lumazine to form
their end products.
XD = xanthopterin deaminase
XO = xanthine oxidase
I = isomerase
Ring-hydroxylated pterins are formed in a manner
completely analogous to the reactions in the lumazine
seriesEs6].Depending upon the presence or absence of the
different pteridine deaminases, the catabolism of pteridines
results in either simple pterins or simple lumazines. Pterin
( 3 ) and lumazine ( 4 ) undergo the same reaction in the
presence of xanthine oxidase : both pteridines are hydroxylated at C-7[60,611. The 7,8-dihydro derivatives
however are attacked at C-6[571.
Forrest et
found that pterin (3) occurs in the ry2
mutant of Drosophila rnelanogaster which lacks xanthine
oxidase while the wild strain has isoxanthopterin (38) in
its place. After injection of radioactive pterin into pupae
of the butterfly Colias croceus, D e ~ c i m o n [showed
~ ~ ] that
radioactive isoxanthopterin was accumulated while injection of tetrahydropterin led to accumulation of labeled isoxanthopterin (38),xanthopterin (3S),and leucopterin (37).
H a r m ~ e n ' ~raised
~ 1 pupae of the butterfly Mylothris chloris
The question arises whether the simple oxidized pterins
and lumazines are in general further degraded by organisms or represent true terminal catabolites. This problem
was studied by Gyure and C ~ r r i g a n " ~in] several species
of insects. In the case of the silkworm Bombyx mori,
homogenates deaminated isoxanthopterin (38) by a highly
specific deaminase. The product, 7-hydroxylumazine (30),
was not further metabolized. When synthetic 6-hydroxylumazine was added to the homogenates, 6,7dihydroxylumazine (34) was formed by the catalytic action of
xanthine oxidase. The 6,7-dihydroxylumazine was not
further catabolized by the homogenates.
The same results were obtained with the cockroach Periplaneta americana and the silkworms Hyalophora cecropia
and. Rothschildia orizaba. When the cockroach Brysotria
fumigata and the firebug Pyrrochoris apterus were studied
they were found to perform the same or similar reactions ;
however they possessed pterin deaminase activity similar
to that found in rat tissues. In all these insects 7-hydroxylumazine was formed but not further catabolized. Since
7-hydroxylumazine is naturally found in Bombyx mori,
Hyalophora cecropia, Rothschildia orizaba, and Pyrrochoris
apterus it is most probably a terminal catabolite in these
Homogenates prepared from the relatively pteridine-rich
butterfliesPieris rapaeand Coliaseurythernedid not degrade
Angew. Chem. internat. Edit. / Val. I 1 (1972) / No. I 2
isoxanthopterin, leucopterin, 7-hydroxylumazine, or 6,7dihydroxylumazine. Since pterin deaminase activity was
not observed, isoxanthopterin and leucopterin appear to
be the terminal catabolites in these two insects. These data
show that among the organisms studied only the bacterium
Alcaligenes was capable of fully degrading the pteridine
ring while the rat and the insects described end their
catabolism at the stage of simple pteridines and lumazines.
The properties of the pteridine deaminases listed in Table 5
are very similar to one another with the exception of
sepiapterin deaminase. Comparison with the properties
of guanine deaminase (guanase) indicates that there are
similarities here too. Guanase has the same pH optimum,
pteridine (39) Eder and Rembold[68.691 noted that, after
intraperitoneal injection into the rat, this pteridine was
quickly detoxified by catabolism to the 6-hydroxymethyl
(40) and the 6-carboxylic acid derivative (41).
The first oxidation product (40) has only weak diuretic
action while the second (41) is pharmacologically inactive.
The enzymatic reaction is another example of the importance of position 6 of the pteridine ring. This position
is attacked in preference to position 7. Such an importance
can also be seen in the fact that biopterin is a growth factor
for Crithidia fasciculata while the isomer of biopterin
bearing the side chain in position 7 is completely without
Table 5. Comparison of the characteristics of different pteridine deaminases.
B. mori
P . americana
isoxanthopterin isoxanthopterin
deaminase [15] deaminase [15]
B. mori
deaminase [53,67]
Characteristic A . faecalis
pterin deaminase [66]
Rat liver
pterin deaminase [SS]
pH optimum
unstable at pH 6.5 and unstable at pH 7 unstable at pH 7
4°C; activity decreases and 0°C
and 0°C; activity
50% in 5 days
decreases 50%
in 7 days
isoxanthopterin isoxanthopterin
> pterin > isoxanthopterin
KCN, lumazine,
unstable at pH 7 and
0°C; stable at pH 9
and 0 "C
pterin and all
p-chloromercuribenzoate, NaF
5.9 x 10-"rnol/l
and isosepiapterin
xan thopterin
it catalyzes an irreversible deamination reaction, and it is
also inhibited by xanthopterin['51. These similarities may
point to a common mechanism of action.
In contrast to these enzymes, sepiapterin deaminase from
Bombyx mori has very different properties. However it
must be noted that its substrate is a 7,8-dihydropterin while
the other deaminases utilize the oxidized, or aromatic
pteridines. Exceptions are the pterin deaminases from rat
liver[*51 and Drosophila melanogaster['sl which can catalyze the deamination of both aromatic and reduced pterins.
The substrate specificityof the deaminases for the pteridines
alone is in marked contrast to xanthine oxidase which
catalyzes oxidations of both purines and pteridines.
Guanase and uricase from bacteria, fungi, insects, and
mammalian sources utilize no pteridine as substrate;
conversely no purine acts as substrate for the pterin
deaminases" 'I.
Numerous synthetic pteridines possess diuretic action. In
investigations with the diuretic 2,4-diamino-6,7-dimethyl-
4. Cofactor Functions
Reduced pterins play a functional role in nature by acting
as cofactors in a number of oxygenase reactions. Kaufman["1 was the first to show this when he reported that
reduced biopterin serves as the natural cofactor in the
hydroxylation of phenylalanine['03'. The reduced pterin
in its inactive 7,8-dihydro form (19) is converted into the
tetrahydro form (42) and after releasing two reducing
equivalents it is converted to a quinonoid-dihydro form
(43) [721. The tetrahydropterin structure is regenerated
from the quinonoid form by the action of i i i i NADPHdependent dihydropterin reductase.
The pteridine in this hydroxylation reaction h;is been
shown to be specific since other reductaniz. wch as
ascorbate, glutathione, ferrous ions, etc., are incapable of
replacing the reduced pterin. The pterin functions catalytically, i.e. when a regenerating system is present a small
amount of tetrahydrobiopterin will serve to catalyze the
oxidation of greater amounts of substrate. Reduced biopterin has also been shown to be consumed stoichiometrically in the reaction and this utilization is substrate and
enzyme dependent[731.Further studies by Osanai and
R e r n b ~ l dhave
~ ~ demonstrated
that of the four isomers of
biopterin the L-erythro-tetrahydrobiopterin isomer is by
far the best cofactor in the rat liver system.
A reduced pteridine also functions as a cofactor for
Pseudomonas phenylalanine hydroxyla~e'~
'I. The structure
of the natural cofactor in this system has not yet been identiAngew. Chem. internat. Edit. 1 Val. I 1 (1972) / No. 12
reductase + NADPH
fied but it is known that Pseudomonas can accomplish the
de nouo synthesis of the pteridine ring and the necessary
cofactor for the reaction[761.When pteridines are extracted
from this organism L-threo-neopterin occurs in the greatest
amount followed by 6-pterincarboxylic acid, pterin, and
xanthopterin. No biopterin was observed. Since reduced
neopterin functions as well as tetrahydrobiopterin in the
Pseudomonas system it may represent the natural cofactor.
Tyrosine hydroxylase has been highly purified from bovine
adrenal medulla[771.Tetrahydrobiopterin also seems to
be the natural cofactor for this enzyme‘”01. In all other
oxygenase systems in which reduced pteridines have been
suggested as cofactors the natural cofactor has not been
identified or proved to be a pteridine. However, at least
one of these other systems has been shown to utilize reduced
pteridines specifically, catalytically, and also stoichiometrically. This system is the rat liver enzyme preparation
which catalyzes the conversion of long chain alkyl ethers
of glycerol to fatty acids and glycerol[781.
Other less well characterized reactions neverthelessshowing
considerable dependence on reduced pteridines are listed
in Table 6. More studies are necessary to validate these
Because reduced pteridines are active reagents in their own
right, it is not surprising that recent reports have demonstrated that in the presence of Fez+ tetrahydropterins in
molar excess can act as non-specific hydroxylation agents
for aromatic amino acids1a0.
12). With these pteridine
characteristics in mind the reactions in Table 6 should be
restudied. Nevertheless it is significant that when Rembold
and Hanser injected labeled biopterin and neopterin into
bee pupae[”’and into the rat‘371radioactivity was found in
cells of high metabolic activity such as bee cuticle at the
time of sclerotization, bee fat body, rat liver, and the
peripheral ganglion sheath of the rat central nervous
system. These are exactly the locations required of cofactors for tyrosine hydroxylase, phenylalanine hydroxylase, and the alkyl ether hydroxylase. Similar findings have
been reported by Kokolis and ZieglerlS3]who noted that
high concentrations of tetrahydrobiopterin (42) were
localized in regenerating portions of the tails of Triturus
5. Hydrogenated Pterins in Cellular Electron
Recent studies, especially those on redox potentials, point
to the probable importance of pteridines in cellular electron
transportr911. The polarographic halfwave potentials of
the aromatic pteridines are similar to those of the pyridine
~ ~ .standard halfwave potential of 6,7dimethyltetrahydropterin is + 150 mV‘931,which is similar
to those of the cytochromes (Table 7). EPR measurements
show the possibility that this tetrahydropterin can form a
cationic radical under physiological conditions[941.
Table 7. Standard redox potentials Ebof components of the respiratory
chain compared with 6,7-dimethyltetrahydropterin (DMTH).
Cytochrome a/a,
Cytochrome c
Cytochrome c I
Cytochrome h
- 0.05
Table 6. Enzyme reactions reported to involve pteridine cofactors
Tryptophan 5-hydroxylase
tryptophan to S-hydroxytryptophan
cinnamic acid top-cumaric acid
anthranilic acid to hydroxyanthranilic acid
progesterone to 17-hydroxyprogesterone
proline to hydroxyproline
prostaglandin biosynthesis
ethanol to acetaldehyde
Cinnamic acid hydroxylase
Anthranilic acid hydroxylase
Progesterone 17-hydroxylase
Proline hydroxylase
Prostaglandin synthetase
Pseudomonas alcohol dehydrogenase
reported pteridine-dependent reactions, especially since it
has been shown that reduced pteridines can stimulate an
enzyme-catalyzed reaction by protecting the enzyme from
These findings, although not conclusive, support the hypothesis of Fuller and N u g e n ~ Ithat
~ ~ ]pteridines are primary
electron receptors in photosynthesis. According to these
authors, a trihydropteridine radical is the electron receptor
in the photosynthetic light reaction, and a tetrahydropteridine is thereby formed which then reduces ferredoxin.
The hypothesis isnot supported by the fact that the standard
potential for tetrahydropterins is +0.15 V while for
ferredoxin it is -0.42 V. From these potentials a reverse
sequence of electron flow, i.e.. the reduction of an oxidized
pterin by a reduced ferredexin, would be the expected
reaction. Further studies will help to solve this question.
The occurrence of pteridines in chloroplasts has not been
clearly demonstrated. It is possible that the few simple
pteridines isolated from plants are decomposition products
Angew. Chem. infernat. Edit. Vol. 11 (1972) No. 12
of folic acid or riboflavin. The fiinction of pteridines in
mitochondria is much clearer. By isotopic dilution methods
a significant amount' of tetrahydrobiopterin ( 4 2 ) has been
detected in these organelles[' 'I. Reduced pteridines in
physiological concentrations stimulate mitochondria1 respiration and the utilization of oxygen has been found to
be linearly proportional to the amount of tetrahydropteridine present. At a concentration of reduced pterin
which is five times higher than the physiological concentration the linearity of the oxygen utilization levels to a
Low temperature difference spectra show the reduction of
the respiratory chain at the cytochrome c and a/a3 sites.
Cytochrome c1 is not reduced even though its redox
potential makes it appear a likely candidate (Table 7). It is
noteworthy that respiration is not coupled to ATP production in the presence of tetrahydropterins. Obviously the
electrons must flow from the tetrahydropteridine. cia
cytochrome c, directly to cytochrome o~idase['~'. A
soluble electron transport system can be formed (Scheme 1).
in the integument. Tsujitu and S a k u ~ u $ ~have
' ~ shown that
in Bombyx larvae pteridines and purines are bound to
specific proteins and are localized in integument pteridine
granules. There are specific binding proteins for uric acid,
sepiapterin (7b), and isoxanthopterin (38). It is not yet
ID = isoxanthopterin d e a m i n a s e
known if such proteins exist also for deaminated sepiapterin
and for 7-hydroxylumazine which are the other two pteridines found in Bombyx. Presumably there is either a specific
carrier protein for 7-hydroxylumazine or the carrier for
isoxanthopterin serves also to bind 7-hydroxylumazine.
Because isoxanthopterin deaminase is mainly found in
larval integument, it is clear that 7-hydroxylumazine is
produced and stored in this tissue.
unstable dihydropterin
tet rahydropterin
Scheme I
For an optimal oxidation ofthe reduced pyridinenucleotide,
NADPH, every component of the system is essential.
Tetrahydropterin can also be non-enzymatically regenerated in the system by NADPH probably from an unstable
radical. The system can reduce more material than the
amount of component tetrahydropterin and is limited only
by the NADPH concentration. Therefore tetrahydropterin
has a distinct catalytic effect in the system[16.961. The exact
significance of tetrahydrobiopterin (42j and similar
pteridines in cellular electron transport will have to be
clarified in further studies.
At the beginning of the spinning phase, which occurs at
the start of metamorphosis from larval to pupal form, the
integument loses its creamy white color. It now becomes
clear due to the breakdown of the membrane of the
pteridine granules which in turn releases purines and
pteridines to the cytoplasm and insect hemolymph. That
the poorly soluble 7-hydroxylumazine can be so suddenly
accommodated and transported by the hemolymph is
probably an indication that it is again complexed to a
7-Hydroxylumazine (30j occurs in B o m h y ~eggs in very
small amounts, its presence presumably arising from the
maternal tissues. At the time o f hatching the enzyme
isoxanthopterin deaminase becomes active. This enzyme
in B o m b p has been shown to be responsible for catalyzing
the synthesis of 7-hydroxylumazine (30) from isoxanthopterin (3;Y).
As Bombyx pupal tissues form, the concentration of hemolymph 7-hydroxylumazine rapidly decreases, a portion
being excreted while the rest is stored in the fat body. New
7-hydroxylumazine is not formed in the fat body and the
observable lumazine in this organ represents a transported
and stored compound. This can be deduced from observations on the behavior of isoxanthopterin deaminase. This
enzyme disappears from Bon7hy.1- at the time of the breakdown of larval pteridine granules and at no time does it
ever occur in the fat body. 7-Hydroxylumazine is stored in
the fat body only during the first half of pupal development ;
during the second half it collects in the meconium. After
emergence of the moth a great part of the lumazine is
excreted while the rest remains attached to the meconial
sac membranes. In the last few days of imaginal development, newly forming female wings and integument abruptly
start fresh synthesis of 7-hydroxylumazine. This is accompanied by an equally abrupt appearance of isoxanthopterin
deaminase activity in the same tissues. This effect is not
observed in male silk moths, probably for genetic reasons.
Parallel to the deaminase activity, 7-hydroxylumazine is
found throughout larval development, especially localized
Similar findings to those in Bonibys have been reported
for other insects, fish, and amphibia. Hnrnd'*' has des-
6. Physiological Aspects
Once pteridines have been synthesized by an organism
they can be utilized in situ or they can be transported to
other tissues to be used directly or stored for later needs.
The mechanisms of pteridine transport and storage are not
yet well understood but investigations by Gyure" 5 1 on pteridines in the silkworm Bombyx mori give an insight into the
general physiological process in insects. The results of the
study will therefore bc given in detail.
Angew. Chem. internat. Edit. 1 Vol. I 1 (1972)
1 No. 12
cribed the pteridine granules in various fish, reptiles, and
amphibia. U b i k ~ ' isolated
pterinosomes from lower
vertebrates and found that about 60% of all pteridines
were bound to cell particles. Isoxanthopterin deaminase
and 7-hydroxylumazine display the same localization patterns in the wild silkmoths Hyalophora cecropia and
Rothschildia orizaba as found in Bombyx mori" 'I. Hanser
and Rembold[s2.lool found that after injection of labeled
biopterin into bee pupae radioactivity was located in the
meconial sac membranes.
enzymes already described in Table 3, biosynthetic enzymes
will be soon reported.
In contrast, pteridine catabolism is much clearer especially
since the functions of xanthine oxidase and specific pterin
deaminases are now known. Yet to be answered is the
question whether the pteridine side chain is non-enzymatically split in an organism or whether there is a specific
enzyme which performs this task and which thus can control the concentration of pteridine cofactors.
Worthy of further mention are the studies of Harmsen on
the cabbage butterff y, Pieris brassicaelLO'l.During the
larval and early pupal stages much the same results as
found in Bombyx mori were observed. However, at the
time of the development of adult tissues in the pupae,
pteridines were noted to be synthesized in relatively large
amounts. In this regard Pieridsdiffer from other lepidoptera.
For example, in this species the isoxanthopterin concentration in the adults is thirty times that found in Bombyx.
Ziegler and Harmsen1'' assumed that the large amounts of
pteridines in Pieris brassicae adult wings arise in part from
de novo synthesis in the wings and in part by transport from
the fat body. The results of studies by Watt[461
with the
butterfly Colias eurytheme support this assumption. He
found that incubation of isolated developing wings of
this butterfly with labeled guanine precursors led to
formation of radioactive wing pteridines. On the other
hand D e ~ c i m o n [ ~has
~ ' found that synthetic 6-hydroxymethylpterin injected into Colias croceus pupae could be
recovered from the adult wings. Since this pteridine does
not normally occur in Colias wings it must have been
transported from the site of injection and stored in the
developing wings. L ~ f o n t [ "has
~ ~ noted that, after injection of radioactive isoxanthopterin into Pieris brassicae
pupae, this pteridine could be observed first in the pupal
fat body and later during adult development in the wings,
meconial sac, and eggs. These findings indicate that butterfly wings have separate but parallel capacities for pteridine
synthesis and storage.
7. Conclusion
From the reported findings it appears that purines are
generally utilized as biochemical precursors of the pteridine
ring. A specific GTP-cyclohydrolase has been purified
from a microorganism but even in this case there is
uncertainty about the enzymatic reaction mechanism. The
first tangible product of the purine-pteridine conversion
in Eseherichia C O Z ~ [ ~ ' is
~ ~-erythro-7,8-dihydroneopterh
triphosphate (12) ; in Commonas on the other hand it is
a cyclic ~-erythro-7,8dihydroneopterh2,3'-monophosphate"02! However, the example of the indolyl derivative
(17) shows that the Brown-Shiota scheme of purinepteridine conversion is not universal, even for microorganisms.
Even greater reservations are held with regard to application of the scheme to higher organisms which appear able
to synthesize the pteridine ring de novo. No enzyme of
pteridine biosynthesis has been purified in such a case.
However, one can predict that in view of the anabolic
Fig. 1. Histoautoradiography of liver slices from a rat injected 24 hours
earlier with [2-'4C]tetrahydrobiopterin. The bright shining spots which
occur in the nucleus show the location of radioactivity in the cells. (Photograph by Dr. G . Hanser.)
Pteridines have not been found to be materials for the
formation of high molecular weight substances, and their
primary function appears to be much more that of redox
catalysts which are coupled by specific reactions to the
hydrogen potential of the pyridine nucleotides. In the case
of the synthesis of the precursors of adrenaline (tyrosine,
DOPA) and of serotonin (5-hydroxytryptophan) the
cofactor importance of pteridines is already apparent and
one can expect that this will apply to the other enzymes
listed in Table 6.
The discovery that mitochondria1 respiration is activated
by tetrahydropterins in physiological concentrations throws
up a number of questions concerning the importance of
pteridines in cellular electron transport. Because of their
very small concentration in the cell, pteridines must be
limited to very special regulatory steps. On the other hand,
it is remarkable how ubiquitous the 6-(polyhydroxyalkyl)Angew. Chem. internat. Edit. / Val. I 1 (1972) / No. 12
pteridines are in nature. The autoradiographic data of
Figure 1 show how pteridines are concentrated in the
nucleus of rat cells.
Their physiological behavior shows also that pteridines do
not generally play the role of metabolic end products as
formerly thought. It is therefore necessary to further study
the findings of pr~tein-pteridine'~']and pteridine-flavin
and of energy-dependent selective biopterin
Pteridine binding to DNA[1o61molecules
may be the mec'hanism by which these substances can
function as regulators. Also of regulatory importance
may be the observations on the remarkable difference
between the pteridine patterns in the ant Forrnica p0lj.ctena["'1.
Received: July 21,1971; revised: February 11,1972 [A 908 IE]
German version: Angew. Chem. 84,1088(1972)
[I] F. G . Hopkzns, Nature 40,335 (1889).
[2] H . Wielandand C. Schopf, Ber. Dtsch. Chem. Ges. 58,2178 (1925).
[3] C.Schiipf'and H . Wieland, Ber. Dtsch. Chem. Ges. 59,2067 (1926).
[4] R. Purrmann, Liebigs Ann. Chem. 544. 182 (1940):546,98 (1940);
548,284 (1941).
[S] W . Pjeiderer, Angew. Chem. 75,993(1963);Angew. Chem. internat.
Edit. 3, 114(1964).
[6] R . C . Elderfield and A . C . Mehra in R . C. Elderfield: Heterocyclic
Chemistry. Wiley, New York 1967.vol. 9.p. 1
[7] H . Rembold, H . Melzger, P . Sudershan. and W . Gutensohn, Biochim.
Biophys. Acta 184,386(1969).
[8] I . Ziegler and R . Harmsen, Advan. Insect Physiol. 6, 139 (1969).
[9] H . S. Forrest and C. ran Banlen. Annu. Rev. Microbiol. 24,91(1970).
[lo] T. Hnma, Ann. N.Y. Acad. Sci. 100,.977(1963).
[I 11 L . Buschmann, Dissertation, Universitat Munchen 1963.
[12] H . Rembold and L . Buschmann. Liebigs Ann. Chem. 662,72(1963).
[13] M . Tsujita and S . Sakurai, Japan. J. Genet. 38.97 (1963).
[14] J.M . Lagowskiand H . S. Forrest. Proc Nat. Acad. Sci. USA58, 1541
[15] W . L . Gyure, Dissertation, Tufts University 1970;University Microfilms. Ann. Arbor, Michigan No. 71-13, 749.
1161 K. Buff, Dissertation, Universitat Miinchen 1971.
[17] H . Remhold and L. Buschmann, Hoppe-Seylers 2. Physiol. Chem.
330. 132 (1960).
[l8] H . Remboldand H . Metzger, 2. Naturforsch. 22b, 827 (1967).
[191 I/. C. Deweyand G. W . Kidder. 1. Chromatogr. 31,326(1968).
[20] M . Viscontini and H . Stierlin, Helv. Chim. Acta 45, 2479 (1962).
[21] E . Hndorn and H . K . Mitchell. Proc. Nat. Acad. Sci. USA 37, 650
[227 H . Descimon and M . Barial, J. Chromatogr. 25, 391 (1966).
[23] M . Viscontini, E. Hadorn, and P . Karrer, Helv. Chim. Acta 40,579
[24] J. D. Gerhort and R. J . Maclnryre, Anal. Biochem. 37, 2525(1970).
I253 C . H . Eugsrer, E . F. Frauenfetder, and H . Koch, Helv. Chim. Acta 53,
131 (1970).
[26] V C. Dewey and G . W . Kidder in D. B. McCormick and L . D. Wright
Medhods in Enzymology. Academic Press. New York 1971,voi. 18B.
p. 618.
[27] W . S. McNurt, Anal. Chem. 36, 912(1964).
[28] G. Gurofin 1261,p. 600.
[29] P. Haug, Anal. Biochem. 37,285 (1970).
[30] T. Lloyd, S . Markey, and N . Weiner, Anal Biochem. 42,108(1971).
1311 H . Kraut, W . Pabsr, H . Rembold, and L. Wildemann, Hoppe-Seylers
Z. Physiol. Chem. 332, 101 (1963).
1321 H . S . Forresf, M . McNater, and J. Alexander, J. Insect Physiol. l2,
1411 (1966).
[33] 7:Shiota in M . Florkin and E. H . Stotz: Comprehensive Biochemistry. Elsevier, Amsterdam 1971,vol. 21,p. 111.
ci4j 0". ;il.E x w n in D. Greenberg: Metabr)k:?a&ways. Academic press,
New York 1970,vol. 4,P. ?!?; Advan. Enzymol. 35,35 (1971).
[351 1. Taked? k~
K. Iwai, M . Goto. M . Akino, and Y. Iwanami: Chemistry
a n d "Doiogy of Pteridines. Internat. Acad. Printing Co., Tokyo 1970.
p. 183.
[36] W . Pabst and H . Rembold, Hoppe-Seylers 2. Physiol. Chem. 344,
r371 H. Rembold, unpublished
[38] H . Rembold, V Chandrashekar, and P . Sudershan, Biochim. Biophys. Acta 237,365(1971)
C391 T. Fukushima, Arch. Biochem. Biophys. 139,361(1970).
1401 T. H . D. Jones and G.M . Brown, J. Biol. Chem. 242,3989(1967).
Angew. Chem. inrernai. Edit. / Val. I 1 (1972) 1 No. I 2
1411 A i t . Burg and G . M . Brown. J . Biol. Chem. 243. 2349 (1968).
1421 H.Remhold and G . Hein:. Hoppe-Seylers 2. Physiol. Chem. 352.
1271 (1971).
[43] G . M . Brown in [35]. p. 243.
[44] H . Remhold and L . Buschmann. Chem. Ber 96.1406 (1963).
1451 B. Grecn and H . Rembold. Chem. Ber. 99.2162(1966)
[46] W . B. Wart. J. Biol. Chem. 242.565 (1967).
[47] H . Descimon, Dissertation. Ecole Normale Superieure. Paris 1969
[48] 7 Shioro, R Jackson. and C. M Bough in [35]. p. 265.
[49] J 8 Mnhis and G . '44.Brown. J. Biol. Chem. 245. 3015 (1970).
[SO] r . P. Richc.vand G . M . Brown. J . Biol. Chem. 244.1582(1969)
1511 T. Shioto, C.M . Bough. R. Jackson. and R. A . Dillnrd. Biochemistry 8. 5022(1969).
[52] K . fwai. 0.
Okinaku. M . Ikedn. and N . Suzukiin [35]. p. 281.
[53] M . Tsusue, J. Biochem (Tokyo)6Y. 781 (1971).
[54] M . Matsuborn. Arch. Biochem. Biophys. 126.426(1968).
[55] H . Remhold and F. Simmershnch. Biochim. Biophys. Acta 184. 589
[56] H . Remhold. H . Merzger. and W Gurensohn. Biochlm. Biophys.
Acta 230.117 (1971).
[57] H . Rembold and W . Gutensohn, Biochem. Biophys. Res. Commun.
L58] C. Leuy and W . S. McNurr. Biochemistry 1. 1161 (1962).
[59] W.S . McNutt, J. Biol. Chem. 238,1116(1963).
[60] F. Bergmonn and H . Kwietny. Biochim. Biophys. Acta 28.613 (1 958).
1611 F. Bergmann and H . Kwietnj. Biochim. Biophys. Acta 33, 29 (1959).
[62] H.S.Forrest,E.Gla.ssman,and
H . K . Mitchell,Science124,725(1956).
[63] S . H . Dustmann, Hoppe-Seylers 2. Physiol. Chem. 352,1599(1971).
[64] H. Descimon, C. R . Acad. Sci. D . 268,416(1969).
1651 J . Harmsen, J. Insect Physiol. IS. 2239 (1969).
[66] B. Leuenberg and 0. Hayashi, J. Biol. Chem. 234,955(1959).
[67] M . Tsujita and S . Sakurai. Proc. Jap. Acad. 43,991(1967).
[68] J . Eder and H. Remhold, Z. Anal Chem. 237, 50 (1968).
[69] J. Eder and H . Remhold. Arzneimittel-Forsch. 21, 562 (1971).
[70] H . Rembold and H . Metzger, Hoppe-Seylers Z . Physiol. Chem. 329,
291 (1962).
1711 S. Kaufman, Proc. Nat. Acad. Sci. USA 50, 1085 (1963).
[721 S Kngfmnn, J. Biol. Chem. 239,332 (1964);Advan Enzymol. 35,
245 (1971).
[731 S . Kmfman, Trans. N.Y. Acad. Sci. 26,977(1964).
[74] M . Osanai and H . Rembold, Hoppe-Seylers 2. Physiol. Chem. 352,
1359 (1971).
[75] G. G u r o f a n d C . A . Rhoads, J. Biol. Chem. 242,3641 (1967).
[76] G.Guroff and C . A . Rhoads, J. Biol. Chem. 244,142 (1969).
1771 R. Shiman. M . Akino. and S . Kaufmnn, J. Biol. Chem. 246. 1330
[781 A . Tietz, M . Lindberg, and E. P. Kennedy. J. Biol. Chem. 23Y. 4081
[791 V. G . Zamoni, N . C. Brown, and B N . LnDu, Fed. Proc. 22.232(1963).
1801 W . F. Coulson, M . J . Powers. and J . B. Japson. Biochim. Biophys.
Acta 222,606(1 970).
[811 M . Viscontini and T . Okada. Helv. Chim. Acta 50, 1845 (1967).
[82] G . Hanser and H . Rembohf, Z. Naturforsch 236,666(1968).
1831 N . Kokolis and I. Ziegler, Z. Naturforsch. 2 3 b , 860 (1968).
C841 S Hosoda and D . Click, J. Biol. Chem. 24/,192(1966).
[SSl P. M . Nair and L. C. Vinning. Phytochemistry 4, 161 (1965).
C861 P. M . Nuir and C . S. Vnidyanathan, Phytochemistry 3,235(1964)
[87] D . D . Hagerman. Fed. Proc. 23.480 (1964).
[88l 3.Peterkofiky and S . Lidenfriend, Proc. Nat. Acad. Sci. USA 53,335
[891 B Samuelsson, E. Granstron, and M. Hamberg in S . Bergstrom and
B. Samuelsson . Prostaglandins. Nobel Symposium. Interscience. Stockholm 1967,vol. 2.p. 31.
1901 C. Anthony and L . J . Zafman, Biochem. J. 104.960(1967).
[91] H . Rembold and K . Buffin E. Quagliarielto, S . Papa, and C. S .
Rossi: Energy Transduction in Respiration and Photosynthesis.
Adriatisa Editrice, Bar1 1971,p. "57.
[92] H . Remboldand H . Merzger, Hoppe-Seylers 2. Physiol. Chem. 348,
194 (1967).
[93] M . C. Archer and K . G . Scrimgeour, Can J, B:oi:,eiii. R , 5;ij
LY+ A . M . Bobst, Proc. Nat Acad. Sci. USA68, 541 (1971).
[95] R C . Fuller and N . A . Nugent, Proc. Nat Acad. Sci. USA 63. 131 1
(1 969).
[96] H . Rembold and K . Bufi Eur. J. Biochem. 28, 579,586(1972).
[97] M . Tsujita a n d D. Snkurai, Proc. Jap. Acad. 41, 230 (1965).
[98] S. Katoh, Arch. Biochem. 146,202 (1971).
[99] M . Ubika in [35], p. 413.
[loo] G. Hanserand H . Rembold, 2. Naturforsch 19b.938(1964).
[loll R. Harmsen, J. Insect Physiol. 12.9(1966).
[lo21 J . Cone and G . Guroff, J. Biol. Chem. 246,979(1971)
[lo31 S . Kaufman and D . B. Fisher. J. Biol. Chem. 245,4745 (1970).
[lo41 G . H . Schmidtand M . Viscontini,Helv. Chim. Acta47, 2049(1964).
[lo51 H . Rembold and A . Vaubel. Hoppe-Seylers Z. Physiol. Chem. 351,
11061 H . S . Forrest in 1351. p. 155.
[I071 G . H . Schmidt in [ 3 5 ] . p. 399.
[lo81 S . K u d 7 . M . Nugur. Y. Nnpai, T. Fukushimu, and M. Akinu in [35].
p. 22s.
[lo91 R. Lafonr.C. R.Acid. Sci.DZ73. 1484(1971).
[110] r Lloyd and N . Weiner, Mol. Pharmacol. 7, 569 (1971)
[l I I ] J. Duymun and G . Guruff. Fed. Proc. 30. I141 (1971).
[I I 2 1 L. 1. Woolf. A. JakubuciE. and E. Chan-Henry. Biochem J. 12s.
569 (1971).
[113] A. Suzrrki and M . Guto. Bull Chem. Soc. Jap. 44,1869 11971)
[I 141 K . Lind, Eur. J . Biochem. 25. 560 (1972).
[115] P A . FriedJi7trn, A. H . K u p p e h u n , and S. K ~ I U $ J I UJ.I I B~ol
Chem. 247,4165 (1972).
Thermally Reversible Photoisomerizations[**]
By Gerhard Quinkert[*]
Dedicated to Professor Hadimir Prelog
This article consists of a programmatic part and a pragmatic one. The programmatic aspects
are the establishment of photochemistry, in the broadest definition of its scope, as a developing
field directed toward the elucidation of photobiological phenomena, and an appeal for
the wide development of the hitherto neglected dimension of electronically excited states.
The pragmatic part is the detailed description of the photochemistry of linearly conjugated
cyclohexadienones as an example of a thermally reversible photoisomerization system. The
logicai use of methods for obtaining information about the formal kinetics of light-induced
reactions and for the identification of short-lived transients by low-temperature spectroscopy
is of value to both parts.
1. The Developing Field of Photochemistry
As far as semantics are concerned all the processes
participating in the formation and deactivation of electronically excited molecules are liberally treated as
topics of photochemical interest. The purist's desire to
speak generally of photoprocesses and to distinguish
photophysical events from photochemical ones---intelligible at first sight-is opposed by the consequences
of an obscure division of the field; such a subdivision is
questionable from the standpoint of development of that
part of science which, in the region of molecular dimensions,
deals with interaction between light and matter and
whose most challenging problems lie above all in the complex["*] systems of biology. With the broadest possible
definition of its scope, photochemistry is a wide field
aimed at the unravelling of photobiological phenomena
selected through the processes of ev~lution[****~.
phases of evolution, which have been labeled chemical.
biochemical, and biological['1 without regard for separative
effects, in order to emphasize growing complexity. Photosynthesis, photomorphogenesis, and phototropism are the
principal phenomena by which plant organisms have
adapted themselves to the environmental condition of
light, while the dominant comparable phenomenon in
animal organisms is vision. The photoprocesses of the
light-absorbing receptors are substantially unknown apart
from the visual pigments[*]. Why is this so?
Adaptation to and further development by existing terrestrial light conditions are characteristic of the various
[*] Prof. Dr. G. Quinkert
Institut fur Organische Chemie der Universitat
6 Frdnkfurt,'Main, Robert-Mayer-Strasse 7-- 9 (German))
5th essay on light-induced reactions; based on a lecture to the
General Meeting of the Gesellschaft Deutscher Chem;ke!- on September 14, 1971, in Karlsruhe The 4th essay was ref. [ 3 5 ] .
From the largely indistinct clamour of voices expressing uneasiness over the present structure and role of chemistry there rises a clear
call for a revision of the structure of chemistry and a turning towards
complex problems: see [I - -31.
A guide to photobiological problems are r g the monographs
of [4-61.
Fig. 1. Time Ti'.,:
;d schematized composition ofthe interdisciplinary
complex of photobiology , cf. [9].
Angew. Chern. internat. Edit. 1 Vul. I 1 (1972) / No. I 2
Без категории
Размер файла
1 342 Кб
pteridines, biochemistry
Пожаловаться на содержимое документа