DOCSLIB.ORG

Studies on the Biosynthesis of Porphyrin and Bacteriochlorophyll by Rhodopseudomonas Spheroides 2. the Effects of Ethionine and Threonine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Studies on the Biosynthesis of Porphyrin and Bacteriochlorophyll by Rhodopseudomonas Spheroides 2. the Effects of Ethionine and Threonine 550 Biochem. J. (1962) 83, 550 Studies on the Biosynthesis of Porphyrin and Bacteriochlorophyll by Rhodopseudomonas spheroides 2. THE EFFECTS OF ETHIONINE AND THREONINE BY K. D. GIBSON, A. NEUBERGER AND G. H. TAIT* Department of Chemical Pathology and Medical Research Council Research Group in Enzymology, St Mary'8 Hospital Medical School, London, W. 2 (Received 28 December 1961) Gibson, Neuberger & Tait (1962) mentioned RESULTS briefly that, when ethionine was added to suspen- sions of Rhodop8eudomona8 8pheroides illuminated Effect of ethionine on the 8ynthe8i8 of in 'mixture I' of Lascelles (1956), large amounts of porphyrins and bacteriochlorophyll porphyrin accumulated in the medium, although During investigation of the role of biotin in por- growth and bacteriochlorophyll synthesis were in- phyrin synthesis (Gibson et al. 1962), various in- hibited. This was rather surprising since other hibitors of growth were examined to see whether inhibitors of growth prevented the formation of they would prevent the restoration of growth and porphyrin and bacteriochlorophyll. In the present the synthesis of porphyrins and bacteriochloro- paper the effect of ethionine is described in more phyll when deficient organisms are illuminated in detail. Of a large number of other compounds only the presence of biotin. The compounds tested were threonine was found to have a similar effect. In the DL-p-fluorophenylalanine, 8-azaguanine, 5-bromo- presence of ethionine or threonine the synthesis of uracil and DL-ethionine. The first three are partly bacteriochlorophyll can be restored and porphyrin successful in preventing growth and porphyrin and excretion reduced by methionine or homocysteine. bacteriochlorophyll synthesis when added with These results suggested that ethionine exerts its biotin to biotin-deficient organisms illuminated in effect by interfering with the synthesis or utiliza- mixture I. In the presence of DL-ethionine, al- tion of methionine. This was confirmed when it was though no growth or bacteriochlorophyll synthesis found that the methyl ester group of bacterio- occurs, a large amount of porphyrin is excreted chlorophyll is formed from the methyl group of into the medium, even in the absence of added methionine. Some of these results have been biotin. Table 1 shows the results with DL-ethionine briefly presented earlier (Neuberger, 1961; Gibson, and also with DL-p-fluorophenylalanine. Ethionine Matthew, Neuberger & Tait, 1961). has the same effect on anaerobically grown organisms as it has on aerobically grown organisms (Table 2). Table 2 also shows that the effect of MATERIALS AND METHODS ethionine in promoting accumulation of porphyrins Chemicak decreases as the degree of biotin deficiency of the organisms increases. Identical results are obtained DL-Homocysteine thiolactone was obtained from Mann when organisms deficient in nicotinic acid or Research Laboratories Inc., New York; DL-ethionine from Roche Products Ltd., Welwyn Garden City, Herts; D- thiamine are muminated in mixture I with the ethionine, L-ethionine and DL-homoserine from the Cali- addition of DL-ethionine. fornia Corp. for Biochemical Research, Los Angeles; L- The absorption spectrum over the range 355- [Me-14C]methionine from The Radiochemical Centre, 610 m,u of the porphyrins accumulating in the Amersham, Bucks. The sources of other chemicals were as presence of ethionine is identical with that of the given by Gibson et al. (1962). porphyrins accumulating in its absence. The maximum of the Soret band in N-hydrochloric acid Methods is 401 me. Paper chromatography of the por- The organisms used, the conditions of growth and phyrins in the lutidine-water system of Nicholas & illumination, and the methods used for colorimetric esti- Rimington (1949) shows that no new porphyrins mations and for assaying enzymes were as described by are formed in the presence of ethionine, and none Gibson et al. (1962). of the porphyrins normally present is absent. The major porphyrin both in the presence and absence * Some of this work forms part of a Ph.D. Thesis sub- of ethionine is coproporphyrin. mitted to the University of London in July 1961 by G. H. Ethionine also stimulates porphyrin synthesis Tait. and inhibits formation of bacteriochlorophyll when Vol. 83 VMETEIONINE AND BACTERIOCHLOROPHYLL FORMATION 551 added to organisms illuminated in succinate and ('mixture II') they accumulate porphyrins al- glycine ('mixture IS', see Table 3). As pointed out though they do not grow or form bacteriochloro- by Gibson et al. (1962); (see also Lascelles, 1959), phyll. Ethionine also stimulates porphyrin syn- when organisms are illuminated in aminolaevulate thesis in mixture II, which contains aminolaevulate Table 1. Effect of DL-p-fluorophenylalanine and DL-ethionine on growth and the synthesis of porphyrin and bacteriochlorophyll in mixture I Organisms grown aerobically in the dark in medium S containing 0-8 pumM-biotin were harvested and illumin- ated under standard conditions for 26 hr. in mixture I. DL-p-Fluorophenylalanine (10 mM), DL-ethionine (10 mM) and biotin (40 lam ) were added where stated. In this and subsequent Tables the concentration of bacteriochlorophyll and porphyrins is expressed as pm-moles/ml. of illumination mixture. Non-illuminated controls were kept at 0° in the dark; under these conditions the concentration of bacteriochlorophyll does not alter. Dry wt. of Bacterio- organisms Porphyrins chlorophyll Additions (mg./ml.) (,um-moles/ml.) (pm-moles/ml.) None 1-08 2-8 10-8 p-Fluorophenylalanine 0-60 3.9 7-8 Ethionine 1-26 30-5 7-0 Biotin 3-24 4-9 38-6 p-Fluorophenylalanine + biotin 0-54 4-4 10-5 Ethionine + biotin 1-26 29-0 6-6 None (non-illuminated control) 0-96 1-1 4-9 Table 2. Effect of DL-ethionine on the synthesis of porphyrin and bacteriochlorophyll by normal and biotin-deficient organisms Organisms were grown anaerobically in the light in medium S containing the concentration of biotin stated. They were then illuminated under standard conditions for 20 hr. in mixture I. DL-Ethionine (5 mM) was added where stated. Concn. of biotin in Bacterio- growth medium Additions to Porphyrins chlorophyll (JAmM) illumination mixture (um-moles/ml.) (,um-moles/ml.) 40 None 13-2 17-6 40 DL-Ethionine 57-6 6-4 40 None (non-illuminated control) 0-0 12-2 2 None 4-8 8-0 2 DL-Ethionine 53-3 6-7 2 None (non-illuminated control) 0-0 11-7 0-8 None 3-6 4-7 0-8 DL-Ethionine 32-7 4-0 0-8 None (non-illuminated control) 0-0 8-0 0-4 None 1-8 3-6 0-4 DL-Ethionine 6-3 2-1 0-4 None (non-illuminated control) 0-0 3-3 Table 3. Effect of DL-ethionine on the syntheMsi of porphyrin and bacteriochlorophyU by organisM8 illuminated in different media Organisms grown aerobically in the dark in medium S containing 0-8 pmmi-biotin were harvested, and illumin- ated under standard conditions for 26 hr. in the media stated. DL-Ethionine (10 mM) and biotin (40 &mm) were added where stated. Dry wt. of Bacterio- organisms Porphyrins chlorophyll Medium Additions (mg./ml.) (Jum-moles/ml.) (,um-moles/ml.) Mixture IS None 0-87 3-6 3-7 Mixture IS Biotin 1-86 28-2 8-1 Mixture IS DL-Ethionine 1-17 37-2 3-6 Mixture II None 0-87 11-8 2-3 Mixture II Biotin 0-85 10-7 1-2 Mixture II DL-Ethionine 0-93 38-1 2-9 Non-incubated control 0-93 0-0 1-8 552 K. D. GIBSON, A. NEUBERGER AND G. H. TAIT 1962 (Table 3), but this effect appears to differ in nature Ethionine does not stimulate porphyrin excretion from that in mixture I or IS (see below). when added to organisms incubated aerobically in As shown in Fig. 1, DL-ethionine (final concentra- the dark in mixture I. No porphyrin or bacterio- tion 5 m ), when added to non-deficient organisms chlorophyll is normally formed under these condi- illuminated in mixture I, completely inhibits the tions. For the synthesis ofporphyrins and bacterio- synthesis of bacteriochlorophyll and carotenoids chlorophyll by organisms illuminated in mixture I, and only partly inhibits growth. However, the Lascelles (1956, 1959) found that all the components molar amount of porphyrin accumulating in the were necessary. In the presence of ethionine, presence of ethionine is twice as great as the sum of ammonium phosphate can be omitted. Of the the porphyrin and bacteriochlorophyll formed in metal ions in mixture I (Mg2+, Ca2+, Mn2+), only its absence. In a number of experiments this ratio Mg2+ ions are required for ethionine to show a was 3-4 (Table 4). Table 4 shows that even 0 1 mM- large effect on porphyrin excretion. ethionine stimulates porphyrin production, i.e. at a concentration at which it reduces bacterio- Effect of threonine on the synthesis of chlorophyll synthesis only slightly. At equal con- porphyrins and bacteriochlorophyll centrations of each the ratios of porphyrin accumu- In an attempt to elucidate the mechanism of lating were 1-5:1-2:1-0 for the L-, DL-, and D- action of ethionine, a number of compounds were isomers respectively. tested to see whether they had a similar effect when added to organisms illuminated in mixture I. The compounds, which were all tested at concentrations between 1 and 10 mm, were DL-methionine, DL- 6 120 - homocystine, DL-homocysteine thiolactone, L- 100.g cysteine, reduced glutathione and L- and D-penicil- 4 80 lamine, all of which contain sulphur; choline, 60 $:110 betaine, formaldehyde, DL-serine and methanol, all 24 40P40~0, 20 Zs of which are capable of yielding biologically active iIIuI J *- I C1-fragments; DL-norleucine, which like ethionine is ti 120_ 30 an antagonist of methionine for protein synthesis (Vaughan & Steinberg, 1959); acetic acid, acetalde- 20 0 hyde, ethanol, L-aspartic acid, L-asparagine, DL- I--60 0.
Load more

Recommended publications
  • Spectroscopy of Porphyrins
    BORIS F. KIM and JOSEPH BOHANDY SPECTROSCOPY OF PORPHYRINS Porphyrins are an important class of compounds that are of interest in molecular biology because of the important roles they play in vital biochemical systems such as biochemical energy conversion in animals, oxygen transport in blood, and photosynthetic energy conversion in plants. We are studying the physical properties of the energy states of porphyrins using the techniques of ex­ perimental and theoretical spectroscopy with the aim of contributing to a basic understanding of their biochemical behavior. INTRODUCTION Metalloporphin Porphyrins are a class of complex organic chemical compounds found in such diverse places as crude oil, plants, and human beings. They are, in most cases, tailored to carry out vital chemical transformations in intricate biochemical or biophysical systems. They are the key constituents of chlorophyll in plants and of hemoglobin in animals. Without them, life would y be impossible. t Free base porphin These molecules display a wide range of chemical and physical properties that depend on the structural details of the particular porphyrin molecule. All por­ ~x phyrins are vividly colored and absorb light in the visible and ultraviolet regions of the spectrum. Some exhibit luminescence, paramagnetism, photoconduc­ tion, or semiconduction. Spme are photosensitizers Wavelength (nanometers) or catalysts. Scientists from several disciplines have been interested in unraveling the principles that cause Fig. 1-The chemical structures for the two forms of por· this diversity of properties. phin are shown on the left. A carbon atom and a hydrogen The simplest compound of all porphyrins is por­ atom are understood to be at each apex not attached to a nitrogen atom.
    [Show full text]
  • Electronic Spectroscopy of Free Base Porphyrins and Metalloporphyrins
    Absorption and Fluorescence Spectroscopy of Tetraphenylporphyrin§ and Metallo-Tetraphenylporphyrin Introduction The word porphyrin is derived from the Greek porphura meaning purple, and all porphyrins are intensely coloured1. Porphyrins comprise an important class of molecules that serve nature in a variety of ways. The Metalloporphyrin ring is found in a variety of important biological system where it is the active component of the system or in some ways intimately connected with the activity of the system. Many of these porphyrins synthesized are the basic structure of biological porphyrins which are the active sites of numerous proteins, whose functions range from oxygen transfer and storage (hemoglobin and myoglobin) to electron transfer (cytochrome c, cytochrome oxidase) to energy conversion (chlorophyll). They also have been proven to be efficient sensitizers and catalyst in a number of chemical and photochemical processes especially photodynamic therapy (PDT). The diversity of their functions is due in part to the variety of metals that bind in the “pocket” of the porphyrin ring system (Fig. 1). Figure 1. Metallated Tetraphenylporphyrin Upon metalation the porphyrin ring system deprotonates, forming a dianionic ligand (Fig. 2). The metal ions behave as Lewis acids, accepting lone pairs of electrons ________________________________ § We all need to thank Jay Stephens for synthesizing the H2TPP 2 from the dianionic porphyrin ligand. Unlike most transition metal complexes, their color is due to absorption(s) within the porphyrin ligand involving the excitation of electrons from π to π* porphyrin ring orbitals. Figure 2. Synthesis of Zn(TPP) The electronic absorption spectrum of a typical porphyrin consists of a strong transition to the second excited state (S0 S2) at about 400 nm (the Soret or B band) and a weak transition to the first excited state (S0 S1) at about 550 nm (the Q band).
    [Show full text]
  • Porphyrins & Bile Pigments
    Bio. 2. ASPU. Lectu.6. Prof. Dr. F. ALQuobaili Porphyrins & Bile Pigments • Biomedical Importance These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma, due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. • Metalloporphyrins & Hemoproteins Are Important in Nature Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (==HC—) bridges. A characteristic property of the porphyrins is the formation of complexes with metal ions bound to the nitrogen atom of the pyrrole rings. Examples are the iron porphyrins such as heme of hemoglobin and the magnesium‐containing porphyrin chlorophyll, the photosynthetic pigment of plants. • Natural Porphyrins Have Substituent Side Chains on the Porphin Nucleus The porphyrins found in nature are compounds in which various side chains are substituted for the eight hydrogen atoms numbered in the porphyrin nucleus. As a simple means of showing these substitutions, Fischer proposed a shorthand formula in which the methyne bridges are omitted and a porphyrin with this type of asymmetric substitution is classified as a type III porphyrin.
    [Show full text]
  • Emerging Applications of Porphyrins and Metalloporphyrins in Biomedicine and Diagnostic Magnetic Resonance Imaging
    biosensors Review Emerging Applications of Porphyrins and Metalloporphyrins in Biomedicine and Diagnostic Magnetic Resonance Imaging Muhammad Imran 1,*, Muhammad Ramzan 2,*, Ahmad Kaleem Qureshi 1, Muhammad Azhar Khan 2 and Muhammad Tariq 3 1 Department of Chemistry, Baghdad-Ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; [email protected] 2 Department of Physics, Baghdad-Ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; [email protected] 3 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan; [email protected] * Correspondence: [email protected] (M.I.); [email protected] (M.R.) Received: 26 September 2018; Accepted: 17 October 2018; Published: 19 October 2018 Abstract: In recent years, scientific advancements have constantly increased at a significant rate in the field of biomedical science. Keeping this in view, the application of porphyrins and metalloporphyrins in the field of biomedical science is gaining substantial importance. Porphyrins are the most widely studied tetrapyrrole-based compounds because of their important roles in vital biological processes. The cavity of porphyrins containing four pyrrolic nitrogens is well suited for the binding majority of metal ions to form metalloporphyrins. Porphyrins and metalloporphyrins possess peculiar photochemical, photophysical, and photoredox properties which are tunable through structural modifications. Their beneficial photophysical properties, such as the long wavelength of emission and absorption, high singlet oxygen quantum yield, and low in vivo toxicity, have drawn scientists’ interest to discover new dimensions in the biomedical field. Applications of porphyrins and metalloporphyrins have been pursued in the perspective of contrast agents for magnetic resonance imaging (MRI), photodynamic therapy (PDT) of cancer, bio-imaging, and other biomedical applications.
    [Show full text]
  • Vitamin B12 Promotes Porphyrin Production in Acne-Associated P
    UCLA UCLA Electronic Theses and Dissertations Title Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis Permalink https://escholarship.org/uc/item/9g02d15m Author Johnson, Tremylla Publication Date 2017 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA Los Angeles Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis A dissertation submitted in partial satisfaction of the requirement for the degree Doctor of Philosophy in Molecular and Medical Pharmacology by Tremylla A. Johnson 2017 © Copyright by Tremylla A. Johnson 2017 ABSTRACT OF THE DISSERTATION Porphyrin production and regulation in different Propionibacterium acnes lineages contribute to acne vulgaris pathogenesis by Tremylla A. Johnson Doctor of Philosophy in Molecular & Medical Pharmacology University of California, Los Angeles, 2017 Professor Huiying Li, Chair Propionibacterium acnes is a dominant human skin commensal. It has been implicated in acne pathogenesis, but its role remains unclear. Recent metagenomic studies have revealed that certain P. acnes strains are highly associated with acne, while some others are associated with healthy skin. Little information exists about P. acnes strain-level differences beyond the genomic differences. In this study, I revealed that acne-associated type IA P. acnes strains produced significantly higher levels of porphyrins (a metabolite important in acne development) than health-associated strains (type II). Strains of type IA-1 and type IA-2 produced similar levels of porphyrins. Moreover, porphyrin production in these P. acnes strains is modulated by vitamin B12. On the other hand, health-associated type II strains produced low levels of ii porphyrins and did not respond to vitamin B12.
    [Show full text]
  • Expanding the Eggshell Colour Gamut: Uroerythrin and Bilirubin from Tinamou (Tinamidae) Eggshells Randy Hamchand1, Daniel Hanley2, Richard O
    www.nature.com/scientificreports OPEN Expanding the eggshell colour gamut: uroerythrin and bilirubin from tinamou (Tinamidae) eggshells Randy Hamchand1, Daniel Hanley2, Richard O. Prum3 & Christian Brückner1* To date, only two pigments have been identifed in avian eggshells: rusty-brown protoporphyrin IX and blue-green biliverdin IXα. Most avian eggshell colours can be produced by a mixture of these two tetrapyrrolic pigments. However, tinamou (Tinamidae) eggshells display colours not easily rationalised by combination of these two pigments alone, suggesting the presence of other pigments. Here, through extraction, derivatization, spectroscopy, chromatography, and mass spectrometry, we identify two novel eggshell pigments: yellow–brown tetrapyrrolic bilirubin from the guacamole- green eggshells of Eudromia elegans, and red–orange tripyrrolic uroerythrin from the purplish-brown eggshells of Nothura maculosa. Both pigments are known porphyrin catabolites and are found in the eggshells in conjunction with biliverdin IXα. A colour mixing model using the new pigments and biliverdin reproduces the respective eggshell colours. These discoveries expand our understanding of how eggshell colour diversity is achieved. We suggest that the ability of these pigments to photo- degrade may have an adaptive value for the tinamous. Birds’ eggs are found in an expansive variety of shapes, sizes, and colourings 1. Te diverse array of appearances found across Aves is achieved—in large part—through a combination of structural features, solid or patterned colorations, the use of two diferent dyes, and diferential pigment deposition. Eggshell pigments are embedded within the white calcium carbonate matrix of the egg and within a thin outer proteinaceous layer called the cuticle2–4. Tese pigments are believed to play a key role in crypsis5,6, although other, possibly dynamic 7,8, roles in inter- and intra-species signalling5,9–12 are also possible.
    [Show full text]
  • To a Protoporphyrin. Thus, Type I Porphyrinogens Or Their Respective Porphyrins Reduced Production Oftype III Porphyrin and Hemo
    A SUGGESTED CONTROL GENE MECHANISM FOR THE EXCESSIVE PRODUCTION OF TYPES I AND III PORPHYRINS IN CONGENJ TAL ERYTHROPOIETIC PORPHYRIA* BY C. J. WATSON, W. RUNGE, L. TADDEINI, IRENE BOSSENMAIER, AND RUTH CARDINAL DEPARTMENT OF MEDICINE, UNIVERSITY OF MINNESOTA, MINNEAPOLIS Communicated June 19, 1964 The curious phenotype of erythropoietic porphyria, both human and bovine, is directly related to the large amounts of type I porphyrins produced by the develop- ing red cells of the bone marrow. The excessive uroporphyrin (URO-) I is respon- sible for the photocutaneous manifestations, as well as the red urine, teeth, and bones. The spleen enlarges and is at least partly responsible for the increased destruction of circulating red cells so often observed. This stimulates erythro- poiesis and heightened formation of porphyrins, as described elsewhere.1-3 It has been proposed4-7 that the genetic error is a deficiency of uroporphyrinogen (UPG) isomerase. This enzyme directs cyclization to UPG III, of the polypyrryl methane first formed from porphobilinogen (PBG) by PBG deaminase. UPG III is preferentially converted by a decarboxylase to coproporphyrinogen (CPG) III and this by virtue of a coproporphyrinogenase (CPGase), to the corresponding protoporphyrin (PROTO-) and heme. In the absence or relative paucity of isomerase the polypyrryl methane from PBG cyclizes to UPG I, and is decarboxyl- ated in varying proportion to CPG I. With possible rare and minor exceptions,8 the specificity of CPGase for type III is maintained, and CPG-I is not converted to a protoporphyrin. Thus, type I porphyrinogens or their respective porphyrins are excreted or accumulated. This has been discussed in recent reviews.4-7 If the inborn error were an isomerase deficiency, a markedly reduced production of type III porphyrin and hemoglobin might be anticipated.
    [Show full text]
  • Biliverdin Reductase: a Major Physiologic Cytoprotectant
    Biliverdin reductase: A major physiologic cytoprotectant David E. Baran˜ ano*, Mahil Rao*, Christopher D. Ferris†, and Solomon H. Snyder*‡§¶ Departments of *Neuroscience, ‡Pharmacology and Molecular Sciences, and §Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and †Department of Medicine, Division of Gastroenterology, C-2104 Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232-2279 Contributed by Solomon H. Snyder, October 16, 2002 Bilirubin, an abundant pigment that causes jaundice, has long hypothesize that bilirubin acts in a catalytic fashion whereby lacked any clear physiologic role. It arises from enzymatic reduction bilirubin oxidized to biliverdin is rapidly reduced back to bili- by biliverdin reductase of biliverdin, a product of heme oxygenase rubin, a process that could readily afford 10,000-fold amplifica- activity. Bilirubin is a potent antioxidant that we show can protect tion (13). Here we establish that a redox cycle based on BVRA cells from a 10,000-fold excess of H2O2. We report that bilirubin is activity provides physiologic cytoprotection as BVRA depletion a major physiologic antioxidant cytoprotectant. Thus, cellular de- exacerbates the formation of reactive oxygen species (ROS) and pletion of bilirubin by RNA interference markedly augments tissue augments cell death. levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic Methods antioxidant cytoprotectant, elicits lesser increases in reactive ox- All chemicals were obtained from Sigma unless otherwise ygen species and cell death. The potent physiologic antioxidant indicated. actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then Cell Culture and Viability Measurements.
    [Show full text]
  • The Porphyrin Handbook
    ThePorphyrinHandbook Editors KarlM.Kadish DepartmentofChemistry UniversityofHouston Houston,Texas KevinM.Smith DepartmentofChemistry UniversityofCalifornia,Davis Davis,California RogerGuilard FaculteÂdesSciencesGabriel UniversiteÂdeBourgogne Dijon,France SANDIEGOSANFRANCISCO NEWYORKBOSTON LONDONSYDNEY TORONTO Preface The broadly de®ned porphyrin research area is one of the this is a data-intensive ®eld, and we believe that compilation most exciting, stimulating and rewarding for scientists in the of relevant data should be useful to investigators. We have ®elds of chemistry, physics, biology and medicine. The attempted to ensure that every chapter was written by the beautifully constructed porphyrinoid ligand, perfected over currently acknowledged expert in the ®eld, and very early on the course of evolution, provides the chromophore for a we had in our hands no less than sixty-nine signed contracts multitude of iron, magnesium, cobalt and nickel complexes for chapters. With the fullness of time, and as deadlines for which are primary metabolites and without which life itself Handbook chapter submission and other essential activities could not be maintained. (e.g., research proposal renewals) converged, some of our Falk's book, Porphyrins and Metalloporphyrins, pub- authors had to withdraw. On occasion we were able to lished in 1962, was a fairly thin volume which represented recruit new authors who, with only a month or less of lead the ®rst attempt to apply the principles of modern chemistry time, were able to ®ll these gaps and come
    [Show full text]
  • Hereditary Coproporphyria: Incidence in a Large English Family *
    J Med Genet: first published as 10.1136/jmg.21.5.341 on 1 October 1984. Downloaded from Journal ofMedical Genetics, 1984, 21, 341-349 Hereditary coproporphyria: incidence in a large English family * J ANDREWSt, H ERDJUMENT+, AND D C NICHOLSON+ From the tDepartment of Geriatric Medicine, West Middlesex University Hospital, Isleworth, Middlesex; and ithe Department of Chemical Pathology, King's College Hospital Medical School, London SE5. SUMMARY In a family inheiiting the hereditary coproporphyria (HCP) gene, where 414 descendants have been traced through six generations and 135 members screened for faecal porphyrins, 27 subjects were found to have inherited the gene as well as the proband. Seven (six female and one male) in retrospect had probably previously suffered from a clinical attack of porphyria. Enzy- mological studies were carried out on 15 members and two unaffected parents and these results in general agreed with the faecal coproporphyrin readings. Symptomatic illness is low in HCP and is almost always precipitated by drugs known to have an adverse effect on the condition. If the gene is inherited, an attack can occur at any time between puberty and old age, such as in the proband at 84 years. We have detected abnormal faecal copro- porphyrin levels in members of this pedigree as young as 12 years and as old as 87 years. Recommendations are given concerning the necessity of tracing relatives who may have inherited the gene and arranging for their biochemical screening and genetic counselling if indicated. copyright. Dobriner1 first described the presence of excessive drug history was taken. Porphyrin estimations on the amounts of coproporphyrin isomer III in certain faeces were then carried out on the oldest surviving patients and the first clinical description was members ofeach branch of the family and, ifpositive, recorded in 1949.2 Smaller family series have been all the next generation and their progeny, if indi- reported by Haeger-Aronsen et al,3 Dean and cated, were tested.
    [Show full text]
  • Physiological Roles of Animal Succinate Thiokinases
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Volume 230, number 1,2, 6-8 FEB 05670 March 1988 Physiological roles of animal succinate thiokinases Specific association of the guanine nucleotide-linked enzyme with haem biosynthesis T.M. Jenkins and P.D.J. Weitzrnan Department of Biochemistry, University of Bath, Bath BA2 7AY, England Received 25 January 1988 The discovery of two distinct succinate thiokinases in mammalian tissues, one (G-STK) specific for GDP/GTP and the other (A-STK) for ADP/ATP, poses the question of their differential metabolic roles. Evidence has suggested that the A-STK functions in the citric acid cycle in the direction of succinyl-CoA breakdown (and ATP formation) whereas one role of the G-STK appears to be the re-cycling of succinate to succinyl-CoA (at the expense of GTP) for the purpose of ketone body activation. A third metabolic participation of succinyl-CoA is in haem biosynthesis. This communication shows that in chemically induced hepatic porphyria, when the demand for succinyl-CoA is increased, it is the level of G-STK only which is elevated, that of A-STK being unatlected. The results implicate G-STK in the provision of succinyl- CoA for haem biosynthesis, a conclusion which is further supported by the observation of a high G-STK/A-STK ratio in bone marrow. Succinate thiokinase; Guanine nucleotide; Heme synthesis; Porphyrin synthesis; Porphyria; Mitochondrial metabolism 1. INTRODUCTION tion. In mammalian brain G-STK shows a marked elevation in activity with increased ketone body Mammalian succinate thiokinase (succinyl-CoA utilization [2], thus supporting the proposal that synthetase) (STK) catalyses the following reversi- the recycling of succinate to succinyl-CoA, re- ble reaction: quired for ketone body activation, is achieved directly by the action of G-STK.
    [Show full text]
  • Continuous Chlorophyll Degradation Accompanied by Chlorophyllide and Phytol Reutilization for Chlorophyll Synthesis in Synechocystis Sp
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1767 (2007) 920–929 www.elsevier.com/locate/bbabio Continuous chlorophyll degradation accompanied by chlorophyllide and phytol reutilization for chlorophyll synthesis in Synechocystis sp. PCC 6803 ⁎ Dmitrii Vavilin, Wim Vermaas School of Life Sciences and Center for the Study of Early Events in Photosynthesis, Arizona State University, Box 874501, Tempe, AZ 85287, USA Received 3 January 2007; received in revised form 23 March 2007; accepted 27 March 2007 Available online 3 April 2007 Abstract Chlorophyll synthesis and degradation were analyzed in the cyanobacterium Synechocystis sp. PCC 6803 by incubating cells in the presence of 13C-labeled glucose or 15N-containing salts. Upon mass spectral analysis of chlorophyll isolated from cells grown in the presence of 13C-glucose for different time periods, four chlorophyll pools were detected that differed markedly in the amount of 13C incorporated into the porphyrin (Por) and phytol (Phy) moieties of the molecule. These four pools represent (i) unlabeled chlorophyll (12Por12Phy), (ii) 13C-labeled chlorophyll (13Por13Phy), and (iii, iv) chlorophyll, in which either the porphyrin or the phytol moiety was 13C-labeled, whereas the other constituent of the molecule remained unlabeled (13Por12Phy and 12Por13Phy). The kinetics of 12Por12Phy disappearance, presumably due to chlorophyll de- esterification, and of 13Por12Phy, 12Por13Phy, and 13Por13Phy accumulation due to chlorophyll synthesis provided evidence for continuous chlorophyll turnover in Synechocystis cells. The loss of 12Por12Phy was three-fold faster in a photosystem I-less strain than in a photosystem II- less strain and was accelerated in wild-type cells upon exposure to strong light.
    [Show full text]