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Heme Biosynthesis from Isomeric Uroprophyrinogens.

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[2] c) C. Angst, C. Kratky, A. Eschenmoser, Angew. Chem. 93 (1981) 275; Angew. Chem. I n t . Ed. Engl. 20 (1981) 263; d) S. Ofner, V. Rasetti, B. Zehnder, A. Eschenmoser, Helu. Chim. Acta 64 (1981) 1431.
161 A B,C,D-hexadehydrocorrinate is formed as by-product ( f a . 4%) in the
anaerobic cyclization of a secoporphyrinogen to nickel( 11)-C,D-tetradehydrocorrinates [2c].
[7] F. P. Montforts, Angew. Chem. 93 (1981) 795; Angew. Chem. Int. Ed.
Engl. 20 (I98 I ) 778.
[8] G. M. Badger, R. L. N. Harris, R. A. Jones, Aust. J. Chem. 17 (1964)
1022.
[9] V. Rasetti, B. Krautler, A. Pfaltz, A. Eschenmoser, Angew. Chem. 89
(1977) 475; Angew. Chem. Int. Ed. Engl. 16 (1977) 459.
Heme Biosynthesis from Isomeric
Uroporphyrinogens” *
By Burchard Franck*, Wilfied Bock, and
Udo Wolters
Uroporphyrinogen 111, la, is precursor and key building
block”’ in the biosynthesis of the blood pigment heme
4a121, as well as of related biologically active tetrapyrrolesl’]. Of the three other la-isomers, which differ from
each other by “inversion” of the pyrrole rings (in dotted
circles), only uroporphyrinogen I, 2a, has been found in
nature. Since uroporphyrinogen I, the red dehydration
product of 2a, is deposited in all organs with pathological
disorders of heme biosynthesis (porphyrias) it has been assumed that 2a is not a biosynthetic precursor of 4ar4].We
have now found that uroporphyrinogen I, Za, and even 11,
3a, can be converted enzymically into heme 4a.
Hemolyzed duck blood served as the enzyme system for
the incorporation experiments. In order to enable reliable
statements to be made, the starting materials were dimensioned to correspond to amounts of product in the mmole
region. I4C- and ’H-labeled uroporphyrinogens I, 2b, 11,
3b, 111, lb, and l c were obtained by total syntheses involving 15-22 steps. Selective ’H-labeling of l c was performed using [Mg(py)J2/’H20.
In order to be able to compare the incorporation of the
isomeric uroporphyrinogens unimpaired from variations in
enzyme activity, they were “fed” as pairs, one component
of which was labeled with I4C, the other with ’H, to the enzyme system. Final I4C- and ’H-determination of the heme
4b, which was isolated from these competition experiments and purified to constant radioactivity gave the incorporation values of the uroporphyrinogens (Table I).
Table I . Competitive incorporation of the isomeric uroporphyrinogens
(Uro’gens) 111, Ib, Ic, I , Zb, and 11, 3b into heme 4b over 48 h.
Radioactivity [nCil
Precursor
4b
lncorp.
Experiment
Precursor
1
“C-Uro’gen 111 l b
’H-Uro’gen 111 l c
360
750
34.5
23
9.6
3. I
2
‘T-Uro’gen 1 2b
’H-Uro’gen 111 l c
1920
910
56.6
32.8
2.9
11.2 [a]
3
14C-Uro’genI1 3b
‘H-Uro’gen 111 l c
610
920
10.2
37.3
1.7
12.6 [a]
lU/d
[a] Corrected with the tritium-loss factor from the experiment No. I
(=3.10).
la, R = H
lb, R = H,
Ps
A
I
A
Ps
I‘
.--_
Ps
\
I(
Received: November 16, 1981 [Z 24 IE]
German version: Angew. Chem. 94 (1982) 226
,
’\
Ps
2a
Zb, 14C in a,p , -y,6
The uroporphyrinogens I, 2, and 11, 3, which previously
had not been considered as heme precursors, exhibit significant incorporation values of 2.9 and 1.7%, respectively,
which are only smaller than those of uroporphyrinogen 111,
1, by a factor of 4 to 7. Presumably, inversion of the pyrrole nuclei D and B, respectively, occurs in the enzymic
conversions of 2 and 3 into the blood pigment heme 4a.
3a
3b, I4C in a,y
[I] B. Franck, Angew. Chem. 91 (1979) 453; Angew. Chem. I n t . Ed. Engl. 18
(1979) 429.
[2] B. Franck, D. Gantz, F.-P. Montforts, F. Schmidtchen, Angew. Chem. 84
(1972) 433; Angew. Chem. Int. Ed. Engl. 11 (1972) 421.
131 Reviews: M. Akthar, P. M. Jordan in D. H. R. Barton, W. D. Ollis: Comprehensiue Organic Chemistry. Vol. 5, p. 1121. Pergamon Press, Oxford
1979; B. Franck, Angew. Chem. 94 (1982) and Angew. Chem. Int. Ed.
Engl. 21 (1982), in press.
[4] U. A. Meyer, R. Schmid in J. B. Stanbury, J. B. Wyngarden, D. S. Frederickson: The Metabolic Basis of Inherited Diseases. McGraw-Hill, New
York, 1978 p. 1166.
Me
4a, M = Fe
4b, M = F e C l
By Gottfried Huttner*, Ute Weber, Beate Sigwarth, and
Olaf Scheidsteger
The hornologue of dinitrogen :Sb=Sb: is capable of existence only at high temperatures in the gas phase; simi-
A CH2-CQH
PS = CH,-CH,-COzH
[*I Prof. Dr. B. Franck, W. Bock, U. Wolters
Organisch-chemisches Institut der UniversitPt
Orleans-Ring 23, D-4400 Munster (Germany)
[**I Tetrapyrrole Biosynthesis, Part I5.-Part 14: G. Bringmann, B. Franck,
Liebigs Ann. Chem., in press.
Angew. Chem. Inr. Ed. Engl. 21 (1982) No. 3
Antimony Homologues of Dinitrogen and Azobenzene
as Complex Ligands:
Preparation and Structure of [Sb=Sb(W(CO),},]
and IPhSb=SbPh{W(CO),},I**
[*I
Prof. Dr. G. Huttner. U. Weber, B. Sigwarth, 0. Scheidsteger
Lehrstuhl fur Synthetische Anorganische Chemie der Universitst
Postfach 5570, D-7750 Konstanz (Germany)
[**I This work was supported by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie.
0 Verlag Chemie GmbH. 6940 Weinheim, 1982
0570-0833/82/0303-0215 $02.50/0
215
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uroprophyrinogens, heme, isomeric, biosynthesis
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