Carbon Dioxide Narcosis

Pathogenic and nonpathogenic strains of Cryptobia salmositica cultured in minimum essential medium (MEM) with several monosaccharides, disaccharides and amino acids were observed for differences in multiplication and motility. Metabolic end products (i.e. alanine, aspartate, carbon dioxide, lactate and pyruvate) were measured for logarithmically growing cells under aerobic conditions. The pathogenic strain of C. salmositica multiplied more readily in MEM supplemented with D(-)ribose, D(+)xylose, D(+)galactose, D(+)glucose, D(+)mannose and D(-)fructose. However, there were no significant differences in multiplication when the strains were cultured with the monosaccharide D(-)arabinose. The nonpathogenic strain multiplied significantly better than the pathogenic strain in the presence of the disaccharides alpha-lactose, maltose and sucrose. It also multiplied more readily when the amino acids L-glutamine and D(-)proline were added to MEM. The end products of carbohydrate catabolism under aerobic conditions were alanine, aspartate, carbon dioxide, lactate and pyruvate.

The cryoprotective capacity of end products of anaerobic metabolism was measured using resonance energy transfer studies and stabilization of freeze‐labile enzymes during freeze‐thaw. The most effective end products of anaerobic metabolism at preventing fusion of small unilamellar vesicles during freezing were alanopine, alanine, proprionate, acetate, and lactate. Octopine and strombine were less effective, and ethanol resulted in fusion. Lactate dehydrogenase or phosphofructokinase were protected during freeze‐thaw by all of the end products tested. The possible mechanisms of protection of lipid bilayers and enzymes as well as the implications of these results for the survival of intertidal bivalve molluscs during winter are discussed.

Protein turnover rates in neonates have been calculated largely by measuring urinary [15N]urea enrichment following administration of [15N]glycine. Although ammonia has been increasingly recognized as an end product of nitrogen metabolism, in neonates it yields a different estimate of protein turnover than does urea. Comparisons of ammonia and urea end products in parenterally fed neonates have not previously been reported. A third and independent way of estimating protein turnover, developed for adults, is to use breath 13CO2 as an end product following administration of [1-13C]leucine. We therefore carried out simultaneous measurements of protein turnover in 10 parenterally fed neonates, using the three end products. The infants were clinically stable, weighed 2.6 +/- 0.2 kg, and received 3.1 +/- 0.2 g.kg-1.d-1 of amino acid, 2.2 +/- 0.1 g.kg-1.d-1 of lipids, and an energy intake of 90 +/- 4 kcal.kg-1.d-1 (1 kcal = 4.186 kJ). The turnover estimates derived from the 13CO2 and [15N]urea end products were very similar. The [15N]ammonia end product produced values approximately 66% (p less than 0.01) of the other two. We conclude that the ammonia and urea end products probably originate in different precursor pools. The similarity of the urea and breath carbon dioxide results helps validate the use of the urea end product in studying the nitrogen metabolism of parenterally fed neonates. Ideally in future studies two or more end products should be used, since they provide information about different aspects of the neonates' protein metabolism.

PREVIOUS studies from these laboratories1 have shown that L-3,4-dihydroxyphenylalanine (L-dopa) does not undergo sulphoconjugation in vitro in the cytosol sulphating system of rat tissues whereas dopamine very readily yields a mixture of the 3- and 4-O-sulphates. These observations might therefore serve to explain earlier claims2 that sulphoconjugated dopamine constituted a significant proportion of the amine fraction extractable from rat tissues following the administration of 14C-labelled L-dopa and raises the question of the role of sulphoconjugation in dopamine metabolism. In man this may be of significance in L-dopa therapy in the treatment of Parkinson's disease since such conjugates might represent either intermediates or end products of metabolism.

INTEREST at Oregon State University has been concerned with the physiological mechanism by which inherited differences bring about differences in growth rate and efficiency. When this research was initiated, physiological differences that could logically be expected to have some influence were: (1) differences in appetite in which animals that consume more feed grow more rapidly and efficiently, (2) differences in ability to digest the feed eaten, (3) differences in storage products with more rapidly growing animals storing more protein, (4) differences in metabolism such that some animals can convert the feed eaten into growth with greater efficiency than others. Because information is difficult to obtain on ruminants in a post adsorptive state, studies on precursors and end products of metabolism in the blood and urine seem appropriate.The present study is concerned with certain precursors and end products of protein metabolism in growing beef cattle that differ markedly in growth rate and efficiency of converting feed into body gains.

Urinary excretion of ultraviolet-light-absorbing end products of metabolism was studied in mentally retarded children and schizophrenic adults. Excretion of the major end product of pyrimidine metabolism, pseudouridine (5-ribosyluracil), and one of the catabolic derivatives of nicotinic acid, N-methyl-2-pyridone-5-carboxamide, were both found to be depressed in more than half the mentally retarded children and all the schizophrenic adults studied. In addition, a number of previously unidentified components have been found in both types of mental abnormality, as well as in control subjects, some of which components appear to be present in abnormal quantities.

Oxalic acid and its salts occur as end products of metabolism in a number of plant tissues. When these plants are eaten they may have an adverse effect because oxalates bind calcium and other minerals. While oxalic acid is a normal end product of mammalian metabolism, the consumption of additional oxalic acid may cause stone formation in the urinary tract when the acid is excreted in the urine. Soaking and cooking of foodstuffs high in oxalate will reduce the oxalate content by leaching. The mean daily intake of oxalate in English diets has been calculated to be 70-150 mg, with tea appearing to contribute the greatest proportion of oxalate in these diets; rhubarb, spinach and beet are other common high oxalate-content foods. Vegetarians who consume greater amounts of vegetables will have a higher intake of oxalates, which may reduce calcium availability. This may be an increased risk factor for women, who require greater amounts of calcium in the diet. In humans, diets low in calcium and high in oxalates are not recommended but the occasional consumption of high oxalate foods as part of a nuritious diet does not pose any particular problem.

Two anaerobic, non-spore-forming, non-motile, Gram-negative-staining bacteria, strains YIT 12060(T) and YIT 12061(T), were isolated from human faeces. Cells of strain YIT 12060(T) were coccoid to rod-shaped with round ends, positive for catalase, negative for indole and oxidase production, produced succinic and acetic acids as end products of glucose metabolism in peptone/yeast extract/glucose medium and had a DNA G+C content of 55.2 mol%. The main respiratory quinones were MK-10 (40%) and MK-11 (57%). Fatty acid analysis demonstrated the presence of a high concentration of iso-C(15 : 0) (56%). Following 16S rRNA gene sequence analysis, this strain was found to be most closely related to species of the genus Alistipes, with 90.9-92.6% gene sequence similarities to type strains of this species. Phylogenetic analysis and biochemical data supported the affiliation of strain YIT 12060(T) to the genus Alistipes of the family 'Rikenellaceae'. Strain YIT 12060(T) therefore represents a novel species of the genus Alistipes for which the name Alistipes indistinctus sp. nov. is proposed; the type strain is YIT 12060(T) (=DSM 22520(T)=JCM 16068(T)). Cells of the other isolate, strain YIT 12061(T), were pleomorphic rods that were asaccharolytic, catalase- and oxidase-negative, positive for gelatin hydrolysis and indole production, produced small amounts of succinic, acetic and iso-valeric acids as end products of metabolism in peptone/yeast extract medium and had a DNA G+C content of approximately 42.4 mol%. On the basis of 16S rRNA gene sequence similarity values, this strain was shown to belong to the family 'Porphyromonadaceae' and related to the type strains of Odoribacter splanchnicus (89.6%) and Odoribacter denticanis (86.2%); similarity values with strains of recognized species within the family 'Porphyromonadaceae' were less than 84 %. Biochemical data supported the affiliation of strain YIT 12061(T) to the genus Odoribacter. Strain YIT 12061(T) therefore represents a novel species for which the name Odoribacter laneus sp. nov. is proposed; the type strain is YIT 12061(T) (=DSM 22474(T)=JCM 16069(T)).

We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates (glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose (and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.

Carbon dioxide elimination by cardiomyocytes: a tale of high carbonic anhydrase activity and membrane permeability.

Uric acid is the end product of purine metabolism in some species including man and not in others. In birds and reptiles for example, it is the final metabolite of protein as well as purine degradation. In those organisms in which uric acid is not the terminal excretory product of purine metabolism, the molecule is oxidized to allantoin by the enzyme, urate: O2-oxidoreductase, also called urate oxidase or uricase (Fig. 1). This enzyme which opens the six-membered ring in the purine molecule, is found in various microorganisms, plants, and the livers and kidneys of most animals. In mammals allantoin is generally the major end product of purine metabolism, but in nonmammalian species there is further metabolism of allantoin. Amphibia and te-leost fishes convert allantoin to allantoic acid through the action of the enzyme, allantoinase. The latter opens the five-membered purine ring. Nonteleost fishes contain the enzyme allantoicase which breaks down allantoic acid into urea and glyoxylic acid. Finally, some invertebrates are known to convert urea to ammonia and carbon dioxide through the action of urease.

Introduction Most maternal diseases that affect fetal development probably do so by multiple mechanisms. However, for the purpose of study, it is useful to categorize diseases by mechanism of teratogenesis. Maternal disease can effect fetal development in the following ways: (1) specific effects of metabolic end products or antibodies, (2) placental insufficiency, (3) maternal medications or toxic exposures, (4) infection, and (5) genetic disease. The main focus of this chapter is to discuss maternal disease that has primary effects on fetal development. Placental insufficiency, medication/toxic exposures, infection, and genetic disease are mentioned for the sake of completeness and will be discussed briefly. All maternal illnesses, whether they directly affect the fetus or not, can cause iatrogenic premature delivery in the case of an unstable mother. Specific fetal effects of over- or underproduced metabolic end products or antibodies Maternal diseases that cause specific fetal disease can do so by transplacental passage of a toxic maternal metabolic end product (e.g., high glucose or high androgen), by lack of transplacental passage of an essential maternal metabolic end product (e.g., thyroxine), or by transplacental passage of a maternal antibody. Well-studied maternal diseases that are prototypes for the above-described mechanisms of fetal disease include (1) diabetes mellitus, congenital adrenal hyperplasia, and phenylketonuria (toxic metabolic end product), (2) hypothyroidism (maternal underproduction of an essential metabolic end product), and (3) Grave's disease, systemic lupus erythematosus, and rhesus alloimmunization (maternal antibody transfer). There are many other examples of maternal diseases which affect fetal development. However, the above-mentioned prototypic diseases will be discussed below.

SUMMARYPs. aeruginosa was grown under anaerobic conditions in a synthetic glucose nitrate medium. In the presence of nitrate, carbon dioxide and cellular carbon were the end products of glucose metabolism. The nitrate was reduced almost entirely to gaseous nitrogen or nitrous oxide (18 p.c. of utilised NO3‐N). Continued incubation of anaerobic cultures after the exhaustion of the nitrate did very little to alter the end products of nitrate utilisation, but striking variations were recorded for the glucose utilisation. Up to 11 p.c. of the utilised glucose carbon was recovered as volatile and non‐volatile organic acids. The non‐volatile acids included extensive amounts of lactic and glycollic acids together with smaller quantities of succinic, malic, fumaric, citric, α keto glutaric and oxalacetic acids. The volatile acid was produced in approximately the same quantity in both aerated and anaerobic cultures whether nitrate was present or not. Carbon balances of 100 p.c. were obtained for the anaerobic cultures, but extensive discrepancies in the aerated culture indicated the formation of other undetected end products of glucose metabolism.

Acetobacterium woodii utilizes the Wood-Ljungdahl pathway for reductive synthesis of acetate from carbon dioxide. However, A. woodii can also perform non-acetogenic growth on 1,2-propanediol (1,2-PD) where instead of acetate, equal amounts of propionate and propanol are produced as metabolic end products. Metabolism of 1,2-PD occurs via encapsulated metabolic enzymes within large proteinaceous bodies called bacterial microcompartments. While the genome of A. woodii harbours 11 genes encoding putative alcohol dehydrogenases, the BMC-encapsulated propanol-generating alcohol dehydrogenase remains unidentified. Here, we show that Adh4 of A. woodii is the alcohol dehydrogenase required for propanol/ethanol formation within these microcompartments. It catalyses the NADH-dependent reduction of propionaldehyde or acetaldehyde to propanol or ethanol and primarily functions to recycle NADH within the BMC. Removal of adh4 gene from the A. woodii genome resulted in slow growth on 1,2-PD and the mutant displayed reduced propanol and enhanced propionate formation as a metabolic end product. In sum, the data suggest that Adh4 is responsible for propanol formation within the BMC and is involved in redox balancing in the acetogen, A. woodii.

Using in combination an analysis of (i) the levels of enzyme activities present, (ii) the pool sizes of metabolic intermediates and end products and (iii) the effects of feeding metabolic intermediates, the limitations ℴ flux into tropane alkaloids in a Datura root culture have been examined. This culture, produced by transforming a Datura candida × D. aurea hybrid with Agrobacterium rhizogenes, is found to be highly competent in the biosynthesis of both hyoscyamine and scopolamine as well as a wide range of other hygrine-derived alkaloids. It has been found that, of six enzymes which are involved in this pathway, the two initial activities, ornithine decarboxylase (EC 4.1.1.17) and arginine decarboxylase (EC 4.1.1.19), are present at potentially flux-limiting levels, in contrast to those other enzymes assayed which act further down the pathway. An additional limitation to flux, involving the supply of activated acids for condensation with tropine to form the identified tropoyl and tigloyl derivatives, is also indicated from the observed effect of feeding free acids. The relative contribution to flux limitation caused by these two interacting phenomena is inferred from an analysis of the changing relative levels of metabolic intermediates and end products as cultures mature.