Potential Rate-limiting Step Research Articles

CAMP levels from endogenous and exogenous arachidonic acid in isolated dog lung.

We infused exogenous arachidonic acid (AA) into salt-perfused isolated dog lungs. This led to elevations in adenosine 3',5'-cyclic monophosphate (cAMP) which were from conversion of the AA to cyclooxygenase products. The maximal levels of cAMP occurred at far less than maximal levels of cyclooxygenase products. Next, we infused A 23187 to release endogenous pulmonary AA. This led to elevations in cAMP that were from conversion of this endogenous AA to cyclooxygenase products. The level of these products was far less than maximal levels from exogenous AA. However, maximal levels of cAMP from conversion of endogenous AA were similar to maximal levels of cAMP from conversion of exogenous AA. We conclude that maximal levels of pulmonary cAMP from endogenous or exogenous AA are from conversion of the AA to far less than maximal levels of pulmonary cyclooxygenase products. This indicates that levels of cAMP rather than levels of cyclooxygenase products are a potential rate-limiting step in cAMP-linked pulmonary actions of such products from pulmonary conversion of endogenous or exogenous AA.

Response of ammonia metabolism to acute acidosis

AbstractIt is well recognized that the kidney responds to sustained metabolic acidosis with a variety of metabolic adaptations. The metabolic pathways involved in renal ammonia formation, the potential rate-limiting steps, and the enzymatic modifications that accompany chronic metabolic acidosis have been the subject of several detailed reviews [1–4]. On the other hand, relatively little attention has been focused on the metabolic response which precedes the adaptations that characterize the chronic acidotic state, that is, the effect of acute acidosis or a low pH, per se, on renal metabolism.

Stimulation of alanine transport and metabolism by dibutyryl cyclic AMP in the hepatocytes from fed rats Assessment of transport as a potential rate-limiting step for alanine metabolism

(1) Cyclic AMP stimulated alanine transport in isolated hepatocytes by approx. 30%, in the range 0.2–5 mM alanine. (2) Alanine utilisation was also stimulated by cyclic AMP. The rates of transport and metabolism were comparable, both in the presence and absence of cyclic AMP. (3) At concentrations of alanine above 1 mM, addition of ouabain, or the reduction of the Na + concentration, could partially inhibit transport without affecting the rate of metabolism. (4) At these alanine concentrations, stimulation of metabolism by cyclic AMP was associated with a decrease in the intracellular to extracellular alanine concentration ratio. (5) At alanine concentrations below 0.5 mM, or at higher concentrations when transport was inhibited by reducing the Na + concentration, cyclic AMP caused an increase in the alanine concentration ratio. (6) It is concluded that at concentrations of alanine above 1 mM, alanine transport is not rate-limiting for alanine metabolism in hepatocytes from fed rats, and cyclic AMP stimulates alanine metabolism primarily by an effect on an intracellular reaction. At physiological concentrations of alanine, however, alanine transport appears to be rate-limiting in agreement with a previous report.

Hypolipidemic activity of in vitro inhibitors of hepatic and intestinal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase

A number of agents including a series of 1,3-bis (substituted phenoxy)-2-propanones were screened in vitro for their ability to inhibit hepatic and intestinal microsomal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. Effective inhibitors reduced in vivo hepatic and intestinal glycerolipid production and with one exception also lowered serum triglyceride levels, suggesting that agents which inhibit potential rate-limiting steps of glycerolipid biosynthesis may be effective hypolipidemic agents. Two compounds, 1-methyl-4-piperidyl bis ( p-chlorophenoxy) acetate (Sah 42-348) and 1,3-bis ( p-methylphenoxy)-2-propanone were the best inhibitors of glycerolipid biosynthesis and lipid-lowering agents. The lipid-altering effects of both drugs were compared to chlorophenoxyisobutyrate during high fructose intake in rats. Each agent reduced fructose induced glycerolipid biosynthesis and serum triglyceride levels to similar degrees.

Intestinal Absorption and Blood Flow

LTHOUGH AN EVERTED gut sac can move molecules from mucosal to senosal surfaces, time intact intestine utilizes its circulation as an integral part of the transport process, and blood flow must be considered as a potential rate-limiting step. Time immteraction between the circulation and intestinal absorption is a twoway street: absorption influences blood flow and the reverse holds as well. Digestion, motility, and intestinal energy consumption also affect blood flow, either by direct local stimulation or through distant release of humoral agents.