Theory is developed to explain the carbon isotopic composition of plants. It is shown how diffusion of gaseous CO2 can significantly affect carbon isotopic discrimination. The effects on discrimination by diffusion and carboxylation are integrated, yielding a simple relationship between discrimination and the ratio of the intercellular and atmospheric partial pressures of CO2. The effects of dark respiration and photorespiration are also considered, and it is suggested that they have relatively little effect on discrimination other than via their effects on intercellular p(CO2). It is also suggested that various environmental factors such as light, temperature, salinity and drought will also have effects via changes in intercellular p(CO2). A simple method is suggested for assessing water use efficiencies in the field.

On the Relationship Between Carbon Isotope Discrimination and the Intercellular Carbon Dioxide Concentration in Leaves

A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

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Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

https://www.physiology.org/doi/pdf/10.1152/physrev.00012.2004

Ghrelin: Structure and Function

Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics.

Molecular enzymology of carnitine transfer and transport

1 * Scope and Limitations of the Concept of the Transition State- 2 * Catalytic Power and Transition-State Stabilization- 3 * Quantum-Mechanical Approaches to the Study of Enzymic Transition States and Reaction Paths- 4 * Primary Hydrogen Isotope Effects- 5 * Secondary Hydrogen Isotope Effects- 6 * Solvent Hydrogen Isotope Effects- 7 * Heavy-Atom Isotope Effects in Enzyme-Catalyzed Reactions- 8 * Magnetic-Resonance Approaches to Transition-State Structure- 9 * Mapping Reaction Pathways from Crystallographic Data- 10 * Transition-State Properties in Acyl and Methyl Transfer- 11 * Transition States for Hydrolysis of Acetals, Ketals, Glycosides, and Glycosylamines- 12 * Decarboxylations of ?-Keto Acids and Related Compounds- 13 * The Mechanism of Phosphoryl Transfer- 14 * Intramolecular Reactions and the Relevance of Models- 15 * Transition-State Affinity as a Basis for the Design of Enzyme Inhibitors- 16 * Transition-State Theory and Reaction Mechanism in Drug Action and Drug Design- Author Index

Richard D. Gandour

Papers

Molecular enzymology of carnitine transfer and transport

Transition states of biochemical processes

On the importance of orientation in general base catalysis by carboxylate

Solid-state structural chemistry of lariat ether and BiBLE cation complexes: metal-ion identity and coordination number determine cavity size

Carnitine acetyltransferase: A review of its biology, enzymology, and bioorganic chemistry