[This corrects the article on p. 100 in vol. 41.].

Energy conservation in chemotrophic anaerobic bacteria.

The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

/pdf/heme-oxygenase-1-carbon-monoxide-from-basic-science-to-2rhjm6458g.pdf

Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.

The use of stable carbon isotopes as a means of studying energy flow is increasing in ecology and paleo- ecology. However, secondary fractionation and turnover of stable isotopes in animals are poorly understood pro- cesses. This study shows that tissues of the gerbil (Meriones unguienlatus) have different 613C values when equilibrated on corn (C4) or wheat (C~) diets with constant 13c/1ac contents. Lipids were depleted 3.0%o and hair was enriched 1.0%o relative to the C4 diet. Tissue 6t3C values were ranked hair > brain > muscle > liver > fat. After changing the gerbils to a wheat (C3) diet, isotope ratios of the tissues shifted in the direction of the 6a3C value of the new diet. The rate at which carbon derived from the corn diet was replaced by carbon derived from the wheat diet was ade- quately described by a negative exponential decay model for all tissues examined. More metabolically active tissues such as liver and fat had more rapid turnover rates than less metabolically active tissues such as hair. The half-life for carbon ranged from 6.4 days in liver to 47.5 days in hair. The results of this study have important implications for the use of 6~3C values as indicators of animal diet. Both fractionation and turnover of stable carbon isotopes in animal tissues may obscure the relative contributions of isotopically distinct dietary components (such as C3 vs. C,, or marine vs. terrestrial) if an animal's diet varies through time. These complications deserve attention in any study using stable isotope ratios of animal tissue as dietary indicators and might be minimized by analysis of several tissues or products covering a range of turnover times.

Fractionation and turnover of stable carbon isotopes in animal tissues: Implications for δ13C analysis of diet

The gross composition of the body.

A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of this study was to identify the M phi metabolite(s) that induce these injuries. The stable products of the L-arginine pathway, NO2- and NO3-, were incapable of causing cytostasis under coculture conditions. However, NO2- became cytostatic upon mild acidification, which favors its transformation into nitrogen oxides of greater reactivity. This suggested that NO. (and/or NO2), recently identified as an M phi metabolite of L-arginine, could be a mediator. Authentic NO. caused cytostasis and respiratory inhibition in L1210 cells in a dose-dependent manner. The mitochondrial lesions caused by NO. were confined to complex 1 and 2, a pattern of injury identical to that seen after coculture with activated M phi. Inclusion of NO. scavenger systems prevented cytostasis from developing in M phi-L1210 cocultures. Thus, M phi-generated NO. can account for L-arginine-dependent cytostasis and respiratory inhibition.

/pdf/nitric-oxide-a-macrophage-product-responsible-for-cytostasis-1rftqz5pd8.pdf

Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells

Deuterium as an indicator in the study of intermediary metabolism: vii. studies in bile acid formation

http://www.jbc.org/content/166/2/627.full.pdf

The life span of the human red blood cell.

A new procedure for quantitative analysis by isotope dilution, with application to the determination of amino acids and fatty acids.

Deuterium as an indicator in the study of intermediary metabolism xi. further studies on the biological uptake of deuterium into organic substances, with special reference to fat and cholesterol formation

D. Rittenberg

Papers

Deuterium as an indicator in the study of intermediary metabolism: vii. studies in bile acid formation

The life span of the human red blood cell.

A new procedure for quantitative analysis by isotope dilution, with application to the determination of amino acids and fatty acids.

Deuterium as an indicator in the study of intermediary metabolism xi. further studies on the biological uptake of deuterium into organic substances, with special reference to fat and cholesterol formation

STUDIES IN PROTEIN METABOLISM X. THE METABOLIC ACTIVITY OF BODY PROTEINS INVESTIGATED WITH l (-)-LEUCINE CONTAINING TWO ISOTOPES