Aspects Of Intermediary Metabolism Research Articles

Vanadium accumulation in ascidian coelomic cells is associated with enhanced pentose phosphate pathway capacity but not overall aerobic or anaerobic metabolism

Some suborders of ascidians (sea squirts) accumulate remarkable levels of the heavy metal vanadium while others accumulate negligible amounts. The function of this vanadium is unclear, but enhanced pentose phosphate pathway (PPP) has been implicated in its reduction and accumulation. We compared aspects of intermediary metabolism in coelomic cells from ascidian species that have a wide range of vanadium accumulation including non-accumulators. All species appear to have similar aerobic poise with no apparent link to vanadium accumulation. Similarly, all species examined have a limited anaerobic poise that does not seem to relate to vanadium levels. Based on the activities of phosphoglucose isomerase and glucose-6 phosphate dehydrogenase we demonstrate that, relative to the capacity for entry into glycolysis, vanadium-accumulating species have enhanced capacity to metabolize glucose-6 phosphate via the PPP compared to non-accumulators. This finding provides the first comparative support for enhanced PPP capacity linked to vanadium accumulation in tunicates.

The effects of anti-inflammatory drugs on some aspects of intermediary metabolism.

Abstract The effects of salicylate, 2,4-dinitrophenol, hydrocortisone, dexamethasone, phenylbutazone and chloroquine diphosphate on the incorporation of radioactivity from [14C]glucose and [1,4–14C]succinate into the soluble intermediates of rat liver preparations have been studied. It is concluded that the increased incorporation of radiocarbon into oligosaccharides, phosphates and malic and fumaric acids bears no relation to anti-inflammatory activity in the salicylate group of drugs.

Identification of Multiple Rate-limiting Steps during the Human Mitochondrial Transcription Cycle in Vitro

We have reconstituted human mitochondrial transcription in vitro on DNA oligonucleotide templates representing the light strand and heavy strand-1 promoters using protein components (RNA polymerase and transcription factors A and B2) isolated from Escherichia coli. We show that 1 eq of each transcription factor and polymerase relative to the promoter is required to assemble a functional initiation complex. The light strand promoter is at least 2-fold more efficient than the heavy strand-1 promoter, but this difference cannot be explained solely by the differences in the interaction of the transcription machinery with the different promoters. In both cases, the rate-limiting step for production of the first phosphodiester bond is open complex formation. Open complex formation requires both transcription factors; however, steps immediately thereafter only require transcription factor B2. The concentration of nucleotide required for production of the first dinucleotide product is substantially higher than that required for subsequent cycles of nucleotide addition. In vitro, promoter-specific differences in post-initiation control of transcription exist, as well as a second rate-limiting step that controls conversion of the transcription initiation complex into a transcription elongation complex. Rate-limiting steps of the biochemical pathways are often those that are targeted for regulation. Like the more complex multisubunit transcription systems, multiple steps may exist for control of transcription in human mitochondria. The tools and mechanistic framework presented here will facilitate not only the discovery of mechanisms regulating human mitochondrial transcription but also interrogation of the structure, function, and mechanism of the complexes that are regulated during human mitochondrial transcription.

A new role for caveolae as metabolic platforms

The plasma membrane of cells functions as a barrier to the environment. Caveolae are minute invaginations of the membrane that selectively carry out the exchange of information and materials with the environment, by functioning as organizers of signal transduction and through endocytosis. Recent findings of uptake of different metabolites and of lipid metabolism occurring in caveolae, point to a new general function of caveolae. As gateways for the uptake of nutrients across the plasma membrane, and as platforms for the metabolic conversion of nutrients, especially in adipocytes, caveolae are now emerging as active centers for many aspects of intermediary metabolism, with implications for our understanding of obesity, diabetes and other metabolic disorders.

The pathology of phosphorus deficiency in fish--a review.

Phosphorus (P) is an essential component of fish diets. Its deficiency affects not only hard tissues, where it is responsible for rickets, leading to skeletal malformation, but also influences various aspects of intermediary metabolism, and thus growth and feed conversion. Therefore, optimizing the dietary inclusion level is critical at all times. As the aquaculture industry has expanded, so the effects of P in farm effluents, derived from metabolic and uneaten food sources, have also become recognized. Diets are increasingly formulated on a basis that will not only provide adequate P for fish needs, but also endeavour to ensure minimal acceptable P levels in effluents at the same time. Many variables influence P requirements and P availability in fish diets, so it is inadvisable to feed diets formulated to an assumed minimum dietary requirement level, irrespective of the advantages that such a formulation may provide to environmental impact.

Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia

To examine whether lowering of plasma triglyceride concentrations using the fibrate peroxisome proliferator-activated receptor (PPAR)alpha agonist gemfibrozil would influence insulin sensitivity to various aspects of intermediary metabolism among subjects with type 2 diabetes mellitus. A randomized placebo-controlled double-blind study in 12 subjects with type 2 diabetes were treated for 12 weeks after a 12-week dietary run-in. Insulin sensitivity was assessed using a low-dose incremental intravenous insulin infusion. Gemfibrozil significantly reduced fasting serum triglyceride concentrations (p < 0.001) but had no effect on measures of diabetic control. Neither gemfibrozil nor placebo treatment altered insulin sensitivity of glucose or glycerol metabolism during low-dose insulin infusion, but significant falls in both non-esterified fatty acid (NEFA) (p = 0.003) and ketone concentrations (p = 0.002) were observed after treatment with gemfibrozil. Gemfibrozil does not affect insulin sensitivity to glucose or fat metabolism in type 2 diabetes but enhances the lowering of plasma NEFA concentrations by insulin, probably by reducing hepatic fatty acid synthesis.

Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 ± 11.5 v 22.1 ± 2.2 kg · m −2; mean ± SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 ± 3.8 v 2.4 ± 3.0 mU · L −1, P < .001) and remained elevated throughout infusion (F = 492, P < .001), as did C-peptide (F = 22.7, P < .001). Metabolic clearance rate for insulin (MCR I) at the highest infusion rate was similar (1,048 ± 425 v 1,018 ± 357 mL · m −2 · min −1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 ± 108 v 444 ± 68 μmol · m −2 · min −1, P < .01), as was the basal metabolic clearance rate for glucose (MCR G, 77 ± 26 v 108 ± 31 mL · m −2 · min −1, P < .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 ± 0.5 v 1.9 ± 0.5 mmol · L −1, P < .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL · m −2 · min −1/mU · L −1, P < .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were evevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations. Dose-response calculations suggested insulin resistance at physiological insulin concentrations in obesity for glucose, NEFA, glycerol, and ketones.

Substrate interactions in the development of insulin resistance in type II diabetes and obesity

Introduction Theories for the mechanisms underlying the development of insulin resistance have included defects in insulin binding, inhibition of insulin receptor tyrosine kinase, and impaired translocation of glucose across the plasma membrane. However, little attention has been paid to the possibility that altered reciprocal regulatory interactions between lipid and carbohydrate fuels may underly the development of insulin resistance. We would like to review recent developments in metabolic regulation which indicate that this neglected aspect of intermediary metabolism may have more widespread physiological significance than hitherto suspected. The major pathways of glucose utilization are storage (glycogen), non-oxidative degradation (glycolysis) and oxidative degradation. It has been demonstrated in post-absorptive man by indirect calorimetry that the ability of insulin to stimulate non-oxidative disposal of glucose is decreased by the prior oxidation of lipid (Thiebaud, DeFronzo, Jacot et al. 1982). In these studies, a neutral lipid emulsion was infused before insulin concentrations were raised by

Insulin Resistance in Multiple Aspects Of Intermediary Metabolism in Myotonic Dystrophy

The responses of circulating intermediary metabolites to a low-dose incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U · kg−1 · h−1) were examined in eight ambulant subjects with the multisystem disorder, myotonic dystrophy. Eight healthy subjects matched for age, gender, and body mass index served as controls. Oral glucose tolerance (75 g) was normal in all subjects. Basal (postabsorptive) hyperinsulinemia was observed in the subjects with myotonic dystrophy (8.4 ± 2.0 v 2.3 ± 0.2 mU/L, P < .01) with increased basal C-peptide levels. Basal blood glycerol (0.09 ± 0.02 v 0.05 ± 0.01 mmol/L, P < .05), lactate (1.14 ± 0.12 v 0.77 ± 0.07 mmol/L, P < .02), and pyruvate (0.08 ± 0.01 v 0.05 ± 0.01 mmol/L, P < .02) were also elevated in these subjects. During the incremental insulin infusion, circulating insulin (F = 8.2, P < .02) and C-peptide (F = 5.1, P < .05) levels were significantly higher in the myotonic subjects. Despite the hyperinsulinemia, circulating concentrations of lactate (F = 9.8, P < .01), pyruvate (7.8, P < .02), and glycerol (F = 7.5, P < .02) were also higher in the subjects with myotonic dystrophy, providing prima facie evidence of insulin resistance in the regulation of these metabolites. During the highest insulin rate, isotopically determined metabolic clearance rate of glucose was significantly lower in the myotonic subjects (3.6 ± 0.4 v 5.5 ± 0.7 mL · kg−1 · min−1, P < .05), indicating impaired peripheral glucose metabolism. ANOVA confirmed parallel, linear dose-response relationships (P < .005) for plasma insulin (log) and glucose, glycerol, nonesterified fatty acids (NEFA), and total ketone bodies (TKB). For glucose (P < .001), glycerol (P < .001), and NEFA (P < .001), the group regression lines for the subjects with myotonic dystrophy lay parallel to those for the control subjects, but with a significant rightward displacement indicative of insulin resistance. No significant displacement was observed between the group regression lines for TKB. These results indicate that myotonic dystrophy is characterized by insulin resistance in the regulation of multiple aspects of carbohydrate metabolism (glucose, lactate, and pyruvate) and lipolysis (NEFA and glycerol).

4 Clinical aspects of vitamin and trace element metabolism

An adequate provision of all micronutrients, vitamins and essential trace elements is necessary for maintenance of normal tissue function. In patients requiring nutritional support, these factors are essential for optimal utilization of the major nutrients and play a role in all aspects of intermediary metabolism. In this chapter, some of the main features of the micronutrients have been described, together with suggestions regarding their provision enterally or parenterally. For most of these nutrients, diagnostic methods are not available to permit accurate assessment of status and hence the level of provision necessary for optimal results. However, there is now sufficient understanding of nutritional requirements such that few patients should now develop clinical or biochemical signs of under- or overprovision of micronutrients.

Morphology and Physiology of Lamprey Metamorphosis

Metamorphosis is highly synchronized in both landlocked and anadromous sea lampreys, Petromyzon marinus, and can be divided into seven clearly defined stages. Although there may be some subtle internal changes several months before the beginning of external metamorphosis, most internal and external changes are initiated simultaneously in early July in P. marinus. The time and degree to which various external anatomical features take place does not differ to any large degree in landlocked and anadromous sea lampreys. Observations on P. marinus and other lamprey species shows that variations in the time of completion of transformation or development of organs reflect the immediate needs of the animal. For example, transformation of the liver and development of the kidneys occur very early (stage 4) whereas organs and tissues involved in osmoregulation, feeding, and digestion do not reach their definitive adult condition until later stages. All organ systems seem to undergo some morphological transformation during metamorphosis. After the beginning of metamorphosis lipid is utilized as the primary source of energy during the nontrophic period which may last up to 10 mo. Physiological modifications accompanying the initiation of metamorphosis include changes in rate of oxygen consumption, in serum osmolarity and thyroxine levels, in the biochemistry of the blood, and in aspects of intermediary metabolism. There is no definitive information as to the factor(s) which control the metamorphic process in lampreys.Key words: lampreys, metamorphosis, morphology, physiology

Effect of Radiation on Intermediary Metabolism of the Rat

Forty-eight hours after irradiation of rats in the lethal dose range, the amount of CO/sub 2/ in expired air decreased to 75% of the control value. To investigate the reason for this decrease, some aspects of intermediary metabolism were studied by using C/sup 14/-labeled substrates. The fraction of substrate carbon recovered as C/sup 14/O/sub 2/ in expired air (ARO) was significantly reduced postirradiation when the tracers were acetate, ribose, glucose, and fructose. At earlier times, andd with lower doses of radiation, there was either no effect, or there was a decrease that was not statistically significant. The movement of CO/sub 2/ was not affected when NaHC/sup 14/O/sub 3/ was the tracer. The ARO of formate was increased. Irradiation had no influence on the C/sub 6//C/ sub 1/ ratio in C/sup 14/O/sub 2/ when the tracers were glucose-1 and glucose-6. Incorporation of glucose and pyruvate (as alanine) into glycogen was increased severalfold. The transfer of carbon from glucose into urea was impaired by radiation, but that from alanine was not affected. With bicarbonate as the tracer, fixation of CO/sub 2/ in liver glycogen was more than seventy times as great in the irradiated rats as in the controls. These findings aremore » interpreted as follows: the reduced output of CO/sub 2/ in expired air postirradiation is not satisfactorily accounted for by impairment of oxidatton of the substrates used; liver glycogen is increased as a resuit of enhanced glycogenesis and gluconeogenesis; and the increased fixation of CO/sub 2/ in liver glycogen suggests that fat may become an important precursor for gluconeogenesis in the irradiated rat. It was concluded that irradiation in the lethal dose range has an influence on intermediary metabolism the significance of which cannot be evaluated fully with the data at hand.« less

Some aspects of intermediary metabolism in Fasciola hepatica and Polycelis nigra

1. 1. The incorporation of radioactivity from [ 14C]glucose and [1 : 4- 14C 2] into the soluble metabolic intermediates of F. hepatica and P. nigra has been studied. 2. 2. Homogenates of F. hepatica differed from the whole animal in utilizing much less of the labelled glucose and much more of the labelled succinate. 3. 3. Intact P. nigra showed no incorporation of radioactivity from the labelled substrates, whereas its homogenate metabolized 32 per cent of the labelled glucose and 61 per cent of the labelled succinate. 4. 4. The patterns of incorporation of radiocarbon into the soluble metabolic intermediates of the homogenates differed in that F. hepatica formed more radioactive alanine and less radioactive malate, aspartate and citrate from the labelled succinate, whereas P. nigra incorporated more radioactivity from the labelled glucose into alanine.

Symposium on Vitamin Metabolism.

This collection of papers, which describes modern viewpoints on the cellular metabolism of the vitamins, is Number 13 of the Nutrition Symposium Series, and, like its predecessors, it is especially useful to those doing research in this field. Nine separate papers with a complete record of discussions cover many aspects of intermediary metabolism. Opening with a foreword by E. E. Snell and some generalizations by Severo Ochoa, the volume includes details on the biogenesis of riboflavin, the metabolism of thiamine, lipoic acid, nicotinic acid (niacin), pyridoxine hydrochloride (vitamin B 6 ), pantothenic acid, folic acid, ascorbic acid, and biotin. To those who are engaged in the modern clinical search to designate alterations in individual enzymatic reactions as functions of a diseased state, this little volume should be especially valuable in highlighting areas in which additional investigations are required and where what we know about vitamin metabolism might possibly have useful implications