湖南常宁斗岭下二叠统斗岭组的一种床板珊瑚

在湖南南部常宁县斗岭下二叠统斗岭组合煤地层的顶部黑色泥岩中,发现与菊石、腕足类及双壳类动物共生的一种床板珊瑚化石,保存完好,经鉴定为Protomichelinia gangilliigerasp. nov.。 Protomichelinia常见于我国早二叠世地层中,尤其是早二叠世晚期(茅口期)发育较盛,它常与块体状的 Ipciphylium共生。据Flügel(1964)研究,在伊朗北部Mingum和Ruteh流域之东的Zarband Kuh的Ruteh灰岩中,     

贵州剑河寒武系凯里组脊状单臂螺(Haplophrentis carinatus)埋藏特征及与始海百合共生关系探讨

贵州剑河寒武系凯里组软舌螺化石丰富、埋藏形式多样,其中以脊状单臂螺Haplophrentis carinatus化石数量最多、保存最为完整。过去有关学者对凯里组单臂螺化石的研究主要集中在化石分类学方面,对脊状单臂螺埋藏特征及与其他生物共生关系缺乏深入探讨。本文对324块脊状单臂螺化石标本进行系统研究对比后发现,凯里组脊状单臂螺口盖化石埋藏形式有四类:口盖单独保存、口盖以内模或外模化石形式保存、口盖与锥壳完全绞合保存、口盖与锥壳不完全绞合保存;附肢保存较少;锥壳多以内模化石形式保存;脊状单臂螺内模化石与印痕化石上普遍出现类似软体保存形成的三分叉结构,这类三分叉结构属于后期埋藏因素造成的次生结构。文中还对脊状单臂螺与始海百合共生关系进行探讨,并将二者共生关系归为偏害共生。     

外源氧化铁对水稻土中有机酸含量的影响

在水稻土泥浆中添加Fe(OH) 3 可显著降低乙酸浓度 .在新鲜水稻土样品中 ,由于添加Fe(OH) 3导致对乙酸的竞争消耗 ,在培养 5d后 ,乙酸浓度降至 10～ 2 0 μmol·L-1的稳态浓度 ,而此刻对照中的乙酸浓度仍在 12 0 0 μmol·L-1以上 .在乙酸产生量较低的土壤中 ,添加Fe(OH) 3 可完全消耗体系中的乙酸 ,并导致产CH4过程的完全被抑制 .添加纤铁矿同样可使乙酸浓度显著减少 ,但作用效果不如无定形氧化铁 .添加赤铁矿可造成培养初期 (10d以内 )乙酸的大量积累 ,但并不引起产CH4量的增大 .添加Fe(OH) 3 、纤铁矿及铝取代针铁矿 ,能引起厌氧培养的水稻土中丙酸浓度的降低 ,其抑制效率为Fe(OH) 3 >纤铁矿 >铝取代针铁矿 .新鲜土样和经过 11周厌氧处理后的土样中 ,有机酸种类和含量有较大差别 .     

新疆温泉上新世哺乳动物化石

1963年秋,笔者等于新疆博乐塔拉蒙族自治州温泉县大库斯台地方采到一批哺乳动物化石。化石地点他于准噶尔-阿拉套m2南麓,是由新疆地质局第三地质大队贺碧欽等同志首先发现的。化石地点附近的新生代地层可分为四层,自下而上为:1.灰绿色砂岩、细砾岩及土红色砂质泥岩;2.绿灰色泥灰岩及棕红色砂质泥岩;泥灰岩中含碎骨化石;3.桔     

华南埃迪卡拉纪化石保存方式及其时空分布

埃迪卡拉纪化石保存方式具有多样性,包括:磷酸盐化、有机碳质压膜、黄铁矿化、硅化、以及粘土矿物交代。文中综述了以上各种化石保存方式在地层中的时代分布规律、埋藏特征和形成机理,并分析了这些类型的化石库在我国埃迪卡拉纪地层中的地理分布规律和埋藏学意义。分析结果表明:华南埃迪卡拉纪化石库的保存方式主要以有机碳质压膜为主;磷酸盐化和硅化保存方式分布较广;黄铁矿化和粘土矿物交代方式在中国埃迪卡拉纪地层保存较少。有机碳质压膜、黄铁矿化多见于粉砂岩、泥岩中;磷酸盐化、硅化多出现于磷块岩、燧石层或碳酸盐岩的磷质、硅质结核中,化石多为微体化石。另外,多种化石保存方式常常同时出现在同一化石库中,形成复合式的保存模式。     

安徽巢湖早石炭世侏儒型腕足动物群——兼论巢湖地区的泥盆-石炭系界线

本文研究的腕足类材料采自安徽中部巢湖南岸高林村塘埂(插图1)五通群擂鼓台组上部的一层粉砂质粘土岩中,其下紧伏富含Cyclostigma cf,kiltorkense Haughton等植物化石的地层,向上距离含大量腕足类Eochoristites neipentaiensis Chu,Ptychomaletoechia Kinglingensis(Grabau)等的金陵组灰岩层16.5m。与腕足类共生的还有双壳类、腹足类、介形类以及少量植物化石碎片。所有腕足类化石个体微小,属种单调,但保存尚好,属种组合颇具特色,在确定地层时代、进行地层对比和研究腕足类的古生态方面较有意义。     

最早带壳动物化石外壳的矿物学特征

本文对采自我国上扬子地层区内研究较细的若干条前寒武系-寒武系界线剖面的带壳化石进行综合性矿物学研究。借鉴化石钙质骨骼研究方法和成果,运用电镜微区研究及能谱分析资料,就术语的运用、磷质壳与钙质壳之间形成机理的相似性、化石结构的原生及次生性质,以及小壳化石壳壁显微结构分类、演化序列提出一些看法。认为;小壳化石外壳壳质成分大部分为胶磷矿,少量为显微纤状磷灰石,部分为成岩后生作用交代成因的碳酸盐及硅质壳,偶而有原生方解石壳。本文提出此类化石外壳可分原生和次生两大类,其演化序列可简括为:胶粒→层纤、柱状→层纹(片状)。     

北京十三陵地区前寒武纪雾迷山组叠层石和藻席中的藻类群落

北京十三陵地区位于燕山的中段,是华北晚前寒武纪地层发育良好的地区之一。本区雾迷山组厚两千余米,主要分布在萃花山,小宫门东山及卧虎山一带。数年前,笔者在本区萃花山雾迷山组一段采集到一批微小的柱状叠层石与层纹状藻席相互共生的标本,其中一些标本是由黑色燧石组成的。通过切片方法研究,我们发现在一些由黑色燧石组成的叠层石和藻席中保存有多种形态的微化石。作者扼要记述了这些微化石的形态特征,并将这一微化石群与世界其它地区的前寒武纪微生物组合进行比较,并探讨了这一微化石群的生态环境。     

乌桐系底部地层的时代问题

解放以来的数年中,地层上及化石上新的重要发现时有增加。最近潘江同志对于南京龙潭附近的地质研究颇说,曾在雷鼓山剖面鸟桐系的含铁层中发现鱼化石,经刘宪亭同志鉴定,认为胴甲鱼类(Antiarcha)的一种,属名和种名俱未能鉴定,地层时代应属于泥盆纪。因此潘江同志主张将鸟桐系底部的地层,即自高家边层以上的厚约70—80米左右的一段地层归於泥盆纪。这一段的顶部地层是一层深灰色页岩,顶部产胴甲鱼化石及植物化石并含有赤铁矿及褐铁矿结核和瘤状贫铁锰矿,局部呈薄层状。这一层厚约13米含铁的深灰色页岩层,潘江同志主张是上泥盆纪及下石炭纪的分界线,即在此层以上的地层,仍归於下石炭纪底     

湖北宜昌寒武系纽芬兰统岩家河组小壳化石

小壳化石在寒武纪早期地层时代划分中具有重要意义,尤其在寒武系纽芬兰统的区域和洲际对比以及第二阶全球界线层型的确定方面,它们是重要的生物地层对比化石。湖北省宜昌滚子坳剖面寒武系纽芬兰统岩家河组含大量的小壳化石,根据小壳化石带可知岩家河组第1-3层为幸运阶,第5层硅磷质结核灰岩中出现Aldanella yanjiaheensis,表明第5层应属于第二阶。由于第4层炭质灰岩中缺乏化石记录,而不能确定幸运阶和第二阶的地层界线位置。笔者首次在湖北宜昌寒武系纽芬兰统岩家河组第4层上部炭质灰岩处理出一批微体古生物化石,弥补了这一层位化石记录的空缺。通过28个样品的系统分析,笔者获得上千枚小壳个体,系统鉴定和描述了6属10种,其中包括1个未定种和1个新种,新种为肿瘤形盘织金壳Zhijinites tumourifomis sp.nov.。据材料中出现的纽芬兰统第二阶的标准分子Zhijinites longistriatus、其它共生化石组合以及碳同位素地层学等证据,可以推测第4层上部应该属于纽芬兰统第二阶,因此幸运阶和第二阶间的界线位置应该在第4层的中下部。     

Nucleoside phosphorylation by phosphate minerals

In the presence of formamide, crystal phosphate minerals may act as phosphate donors to nucleosides, yielding both 5'- and, to a lesser extent, 3'-phosphorylated forms. With the mineral Libethenite the formation of 5'-AMP can be as high as 6% of the adenosine input and last for at least 10(3) h. At high concentrations, soluble non-mineral phosphate donors (KH(2)PO(4) or 5'-CMP) afford 2'- and 2':3'-cyclic AMP in addition to 5'-and 3'-AMP. The phosphate minerals analyzed were Herderite Ca[BePO(4)F], Hureaulite Mn(2+)(5)(PO(3)(OH)(2)(PO(4))(2)(H(2)O)(4), Libethenite Cu(2+)(2)(PO(4))(OH), Pyromorphite Pb(5)(PO(4))(3)Cl, Turquoise Cu(2+)Al(6)(PO(4))(4)(OH)(8)(H(2)O)(4), Fluorapatite Ca(5)(PO(4))(3)F, Hydroxylapatite Ca(5)(PO(4))(3)OH, Vivianite Fe(2+)(3)(PO(4))(2)(H(2)O)(8), Cornetite Cu(2+)(3)(PO(4))(OH)(3), Pseudomalachite Cu(2+)(5)(PO(4))(2)(OH)(4), Reichenbachite Cu(2+)(5)(PO(4))(2)(OH)(4), and Ludjibaite Cu(2+)(5)(PO(4))(2)(OH)(4)). Based on their behavior in the formamide-driven nucleoside phosphorylation reaction, these minerals can be characterized as: 1) inactive, 2) low level phosphorylating agents, or 3) active phosphorylating agents. Instances were detected (Libethenite and Hydroxylapatite) in which phosphorylation occurs on the mineral surface, followed by release of the phosphorylated compounds. Libethenite and Cornetite markedly protect the beta-glycosidic bond. Thus, activated nucleic monomers can form in a liquid non-aqueous environment in conditions compatible with the thermodynamics of polymerization, providing a solution to the standard-state Gibbs free energy change (DeltaG degrees ') problem, the major obstacle for polymerizations in the liquid phase in plausible prebiotic scenarios.     

Synthesis of analogues of 3-deoxy-D-manno-octulosonic acid (KDO) as potential inhibitors of CMP-KDO synthetase

A series of derivatives of the 2-deoxy analogue of beta-KDO (2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid; ammonium salt, 2) has been synthesised as potential inhibitors of CMP-KDO synthetase, starting from methyl 2,6-anhydro-3-deoxy-4,5:7,8-di-O-isopropylidene-D-glycero-D-talo- octonate and replacing the CO2Me group attached to C-2 variously by CONH2, CONHOH, CH2OH, CH2PO(OH)(O-NH4+), COCH2PO(OH)(O-H3N+pheny), CH2CO2-NH4+, CON-HCH2CO2-NH4+, CONHBn, CONHHexyl, CO2Bn, and CO2Hexyl. Of these derivatives, the hydroxamic acid (CONHOH) was the best inhibitor of CMP-KDO synthetase, but was less potent than 2.     

Marine sulfate-reducing bacteria cause serious corrosion of iron under electroconductive biogenic mineral crust

Iron (Fe(0) ) corrosion in anoxic environments (e.g. inside pipelines), a process entailing considerable economic costs, is largely influenced by microorganisms, in particular sulfate-reducing bacteria (SRB). The process is characterized by formation of black crusts and metal pitting. The mechanism is usually explained by the corrosiveness of formed H(2) S, and scavenge of 'cathodic' H(2) from chemical reaction of Fe(0) with H(2) O. Here we studied peculiar marine SRB that grew lithotrophically with metallic iron as the only electron donor. They degraded up to 72% of iron coupons (10?mm?×?10?mm?×?1?mm) within five months, which is a technologically highly relevant corrosion rate (0.7?mm?Fe(0) year(-1) ), while conventional H(2) -scavenging control strains were not corrosive. The black, hard mineral crust (FeS, FeCO(3) , Mg/CaCO(3) ) deposited on the corroding metal exhibited electrical conductivity (50?S?m(-1) ). This was sufficient to explain the corrosion rate by electron flow from the metal (4Fe(0) →?4Fe(2+) +?8e(-) ) through semiconductive sulfides to the crust-colonizing cells reducing sulfate (8e(-) +?SO(4) (2-) +?9H(+) →?HS(-) +?4H(2) O). Hence, anaerobic microbial iron corrosion obviously bypasses H(2) rather than depends on it. SRB with such corrosive potential were revealed at naturally high numbers at a coastal marine sediment site. Iron coupons buried there were corroded and covered by the characteristic mineral crust. It is speculated that anaerobic biocorrosion is due to the promiscuous use of an ecophysiologically relevant catabolic trait for uptake of external electrons from abiotic or biotic sources in sediments.     

Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1

Heme oxygenase converts heme to biliverdin, iron, and CO in a reaction with two established intermediates, alpha-meso-hydroxyheme and verdoheme. Transient kinetic studies show that the conversion of Fe(3+)-heme to Fe(3+)-verdoheme is biphasic. Electron transfer to the heme (0.11 s(-1) at 4 degrees C and 0.49 s(-1) at 25 degrees C) followed by rapid O(2) binding yields the ferrous dioxy complex. Transfer of an electron (0.056 s(-1) at 4 degrees C and 0.21 s(-1) at 25 degrees C) to this complex triggers the formation of alpha-meso-hydroxyheme and its subsequent O(2)-dependent fragmentation to Fe(3+)-verdoheme. The conversion of Fe(3+)-verdoheme to Fe(3+)-biliverdin is also biphasic. Thus, reduction of Fe(3+) to Fe(2+)-verdoheme (0.15 s(-1) at 4 degrees C and 0.55 s(-1) at 25 degrees C) followed by O(2) binding and an electron transfer produces Fe(3+)-biliverdin (0.025 s(-1) at 4 degrees C and 0.10 s(-1) at 25 degrees C). The conversion of Fe(3+)-biliverdin to free biliverdin is triphasic. Reduction of Fe(3+)-biliverdin (0.035 s(-1) at 4 degrees C and 0.15 s(-1) at 25 degrees C), followed by rapid release of Fe(2+) (0.19 s(-1) at 4 degrees C and 0.39 s(-1) at 25 degrees C), yields the biliverdin-enzyme complex from which biliverdin slowly dissociates (0.007 s(-1) at 4 degrees C and 0.03 s(-1) at 25 degrees C). The rate of Fe(2+) release agrees with the rate of Fe(3+)-biliverdin reduction. Fe(2+) release clearly precedes biliverdin dissociation. In the absence of biliverdin reductase, biliverdin release is the rate-limiting step, but in its presence biliverdin release is accelerated and the overall rate of heme degradation is limited by the conversion of Fe(2+)-verdoheme to the Fe(3+)-biliverdin.     

Chelated iron-catalyzed OH. formation from paraquat radicals and H2O2: mechanism of formate oxidation

Traces of iron, when complexed with either EDTA or diethylenetriaminepentaacetic acid (DTPA), catalyze an OH.-producing reaction between H2O2 and paraquat radical (PQ+.): H2O2 + PQ+.----PQ++ + OH. + OH-.[1]. Kinetic studies show that oxidation of formate induced by this reaction occurs by a Fenton-type mechanism, analagous to that assumed in the metal-catalyzed Haber-Weiss reaction, in which the rate determining step is H2O2 + Fe2+ (chelator)----Fe3+(chelator) + OH. + OH-,[7]; with k7 = 7 X 10(3) M-1 s-1 for EDTA and 8 X 10(2) M-1 s-1 for DTPA at pH 7.4. PQ+. rapidly reduces both Fe3+ (EDTA) and Fe3+ (DTPA), and hence allows both agents to catalyze [1] with comparable efficiency, in contrast to the much lower efficiency reported for the latter as a catalyst for the Haber-Weiss reaction. The catalytic properties of these chelating agents is attributed to their lowering of E0 (Fe3+/Fe2+) by 0.65 V, thus making [7] thermodynamically possible at pH 7. Approximately 2.5% of the OH. produced is consumed by internal or "cage" reactions, which decompose the chelator and produce CO2; however, the majority (97%) diffuses into the bulk solution and participates in competitive reactions with OH. scavengers.     

Biological activity of 1 alpha, 25-dihydroxyvitamin D derivatives--24-epi-1 alpha, 25-dihydroxyvitamin D-2 and 1 alpha,25-dihydroxyvitamin D-7

Biological activity of 24-epi-1 alpha,25-dihydroxyvitamin D-2 (24-epi-1,25(OH)2D2) and 1 alpha,25-dihydroxyvitamin D-7 (1,25(OH)2D7), the 22,23-dihydro derivative of the former compound, was investigated. Both of the vitamin D derivatives stimulated intestinal calcium transport and calcium mobilization from bones in rats; however, the effect was about 50% of that of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)2D3). On the other hand, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 inducement of HL-60 human leukemia cell differentiation was comparable to that of 1,25(OH)2D3. Accordingly, the differentiation-inducing activity of 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 was much greater than their ability to stimulate calcium metabolism. In contrast to 1,25(OH)2D3, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 exerted little hypercalcemic activity in mice. These results suggest that both vitamin D derivatives will be useful as anti-tumor agents.     

The influence of inorganic anions on the formation and stability of Fe3+-transferrin-anion complexes

Harris (Biochemistry 24 (1985) 7412) reports that inorganic anions bind to human apotransferrin in such a way as to perturb the ultraviolet spectrum. The locus of binding is thought to involve the specific metal/anion-binding sites since no perturbation is observed with Fe3+-transferrin-CO3(2-). Paradoxically, we were unable to demonstrate the formation of Fe3+-transferrin-inorganic anion complexes despite the presence of high concentrations of SO4(2-), H2PO4-, Cl-, ClO4- or NO3-. Similar results were found for human lactoferrin. Electron paramagnetic resonance spectroscopy and visible spectrophotometry were used to monitor the results. An attempt to form the H2PO4- complex by displacement of glycine from Fe3+-transferrin-glycine resulted only in the disruption of the ternary complex. A series of inorganic anions varied in their ability to release iron from Fe3+-transferrin-CO3(2-) at pH 5.5, the approximate pH of endosomes where iron release takes place within cells. The order of effectiveness was H2P2O7(2-) much greater than H2PO4- greater than SO4(2-) greater than NO3- greater than Cl- greater than ClO4-. The rate of iron removal from Fe3+-transferrin-CO3(2-) at pH 5.5 by a 4-fold excess of pyrophosphate was greatly enhanced by physiological NaCl concentration. Iron removal was complete within 10 min, the approximate time for iron release from Fe3+-transferrin-CO3(2-) in developing erythroid cells. Thus, inorganic anions may have a significant effect on the release of iron under physiological conditions despite the fact that such inorganic anions cannot act as synergistic anions. The results are discussed in relation to a special role for the carboxylate group in allowing ternary complex formation.     

Generation of *OH initiated by interaction of Fe2+ and Cu+ with dioxygen; comparison with the Fenton chemistry

Iron and copper toxicity has been presumed to involve the formation of hydroxyl radical (*OH) from H2O2 in the Fenton reaction. The aim of this study was to verify that Fe2+-O2 and Cu+-O2 chemistry is capable of generating *OH in the quasi physiological environment of Krebs-Henseleit buffer (KH), and to compare the ability of the Fe2+-O2 system and of the Fenton system (Fe2+ + H2O2) to produce *OH. The addition of Fe2+ and Cu+ (0-20 microM) to KH resulted in a concentration-dependent increase in *OH formation, as measured by the salicylate method. While Fe3+ and Cu2+ (0-20 microM) did not result in *OH formation, these ions mediated significant *OH production in the presence of a number of reducing agents. The *OH yield from the reaction mediated by Fe2+ was increased by exogenous Fe3+ and Cu2+ and was prevented by the deoxygenation of the buffer and reduced by superoxide dismutase, catalase, and desferrioxamine. Addition of 1 microM, 5 microM or 10 microM Fe2+ to a range of H2O2 concentrations (the Fenton system) resulted in a H2O2-concentration-dependent rise in *OH formation. For each Fe2+ concentration tested, the *OH yield doubled when the ratio [H2O2]:[Fe2+] was raised from zero to one. In conclusion: (i) Fe2+-O2 and Cu+-O2 chemistry is capable of promoting *OH generation in the environment of oxygenated KH, in the absence of pre-existing superoxide and/or H2O2, and possibly through a mechanism initiated by the metal autoxidation; (ii) The process is enhanced by contaminating Fe3+ and Cu2+; (iii) In the presence of reducing agents also Fe3+ and Cu2+ promote the *OH formation; (iv) Depending on the actual [H2O2]:[Fe2+] ratio, the efficiency of the Fe2+-O2 chemistry to generate *OH is greater than or, at best, equal to that of the Fe2+-driven Fenton reaction.     

Physiological significance of C-28 hydroxylation in the metabolism of 1alpha,25-dihydroxyvitamin D(2).

In our previous study, we indicated for the first time that C-28 hydroxylation plays a significant role in the metabolism of 1alpha, 25-dihydroxyvitamin D(2) [1alpha,25(OH)(2)D(2)] by identifying 1alpha,24(S),25,28-tetrahydroxyvitamin D(2) [1alpha,24(S),25, 28(OH)(4)D(2)] as a major renal metabolite of 1alpha,25(OH)(2)D(2) [G. S. Reddy and K-Y. Tserng Biochemistry 25, 5328-5336, 1986]. The present study was performed to establish the physiological significance of C-28 hydroxylation in the metabolism of 1alpha, 25(OH)(2)D(2). We perfused rat kidneys in vitro with 1alpha, 25(OH)(2)[26,27-(3)H]D(2) (5 x 10(-10)M) and demonstrated that 1alpha,24(R),25-trihydroxyvitamin D(2) [1alpha,24(R),25(OH)(3)D(2)] and 1alpha,24(S),25,28(OH)(4)D(2) are the only two major physiological metabolites of 1alpha,25(OH)(2)D(2). In the same perfusion experiments, we also noted that there is no conversion of 1alpha,25(OH)(2)D(2) into 1alpha,25,28-trihydroxyvitamin D(2 )[1alpha,25,28(OH)(3)D(2)]. Moreover, 1alpha,24(S),25,28(OH)(4)D(2) is not formed in the perfused rat kidney when synthetic 1alpha,25, 28(OH)(3)D(2) is used as the starting substrate. This finding indicates that C-28 hydroxylation of 1alpha,25(OH)(2)D(2) occurs only after 1alpha,25(OH)(2)D(2) is hydroxylated at C-24 position. At present the enzyme responsible for the C-28 hydroxylation of 1alpha, 24(R),25(OH)(3)D(2) in rat kidney is not known. Recently, it was found that 1alpha,25(OH)(2)D(3)-24-hydroxylase (CYP24) can hydroxylate carbons 23, 24, and 26 of various vitamin D(3) compounds. Thus, it may be speculated that CYP24 may also be responsible for the C-28 hydroxylation of 1alpha,24(R),25(OH)(3)D(2) to form 1alpha, 24(S),25,28(OH)(4)D(2). The biological activity of 1alpha,24(S),25, 28(OH)(4)D(2), determined by its ability to induce intestinal calcium transport and bone calcium resorption in the rat, was found to be almost negligible. Also, 1alpha,24(S),25,28(OH)(4)D(2) exhibited very low binding affinity toward bovine thymus vitamin D receptor. These studies firmly establish that C-28 hydroxylation is an important enzymatic reaction involved in the inactivation of 1alpha,25(OH)(2)D(2) in kidney under physiological conditions.     

Carbon monoxide actuates O(2)-limited heme degradation in the rat brain

The biochemical paradigm for carbon monoxide (CO) is driven by the century-old Warburg hypothesis: CO alters O(2)-dependent functions by binding heme proteins in competitive relation to 1/oxygen partial pressure (PO(2)). High PO(2) thus hastens CO elimination and toxicity resolution, but with more O(2), CO-exposed tissues paradoxically experience less oxidative stress. To help resolve this paradox we tested the Warburg hypothesis using a highly sensitive gas-reduction method to track CO uptake and elimination in brain, heart, and skeletal muscle in situ during and after exogenous CO administration. We found that CO administration does increase tissue CO concentration, but not in strict relation to 1/PO(2). Tissue gas uptake and elimination lag behind blood CO as predicted, but 1/PO(2) vs. [CO] fails even at hyperbaric PO(2). Mechanistically, we established in the brain that cytosol heme concentration increases 10-fold after CO exposure, which sustains intracellular CO content by providing substrate for heme oxygenase (HO) activated after hypoxia when O(2) is resupplied to cells rich in reduced pyridine nucleotides. We further demonstrate by analysis of CO production rates that this heme stress is not due to HO inhibition and that heme accumulation is facilitated by low brain PO(2). The latter becomes rate limiting for HO activity even at physiological PO(2), and the heme stress leads to doubling of brain HO-1 protein. We thus reveal novel biochemical actions of both CO and O(2) that must be accounted for when evaluating oxidative stress and biological signaling by these gases.