fumarates and Acidosis

In order to gain some insight into the fate of fumarate synthesised in the cytosol in the purine nucleotide cycle and in amino acid catabolism, the capability of both rat kidney mitochondria and acidotic rat kidney mitochondria to take up either externally synthesised, via adenylsuccinate lyase, or added fumarate in exchange with intramitochondrial malate or aspartate was tested by means of both spectrophotometric and isotopic techniques. The appearance of either malate or aspartate caused by the presence of fumarate was revealed outside normal and acidotic mitochondria by using specific substrate detecting systems. Consistently, externally added fumarate was found to cause efflux of either [14C]-malate or [14C]-aspartate from loaded mitochondria. The occurrence in rat kidney mitochondria of two separate translocators, i.e., fumarate/malate and fumarate/aspartate carriers, is shown in the light of saturation kinetics and the different inhibitor sensitivity. The fumarate/aspartate antiporters found in normal and acidotic mitochondria appear to differ from each other.

Topics: Acidosis; Adenylosuccinate Lyase; Animals; Aspartic Acid; Biological Transport; Carrier Proteins; Fumarates; Kidney; Malates; Male; Mitochondria; NAD; NADP; Oxaloacetates; Rats; Rats, Wistar

In 28 patients with fulminant hepatic failure alkalaemia was present in 49 of a total of 65 observations. Alkalaemia was due primarlily to a low Pa, C02 in 30 instances and to raised plasma bicarbonate in 16 instances. Blood lactate, pyruvate, and acetoacetate were significantly raised, and in individual cases, blood citrate, succinate, and fumarate were elevated. Blood citrate rose progressively as the clinical condition worsened. Metabolic acidosis was only present in four patients. In three of these patients, all of whom had taken an overdose of paracetamol, the acidosis was severe, present before the onset of clinical heparic failure, and associated with hypoglycaemiaand mild hypotension. In two of these patients the acidosis was shown to be due to accumulation of lactic acid. Plasma free fatty acid concentrations were elevated out of proportion to the degree of ketosis.

Topics: Acetoacetates; Acid-Base Equilibrium; Acidosis; Acute Disease; Alkalosis; Bicarbonates; Carbon Dioxide; Citrates; Fatty Acids, Nonesterified; Fumarates; Hepatic Encephalopathy; Humans; Ketoglutaric Acids; Ketone Bodies; Lactates; Liver Diseases; Oxygen; Partial Pressure; Pyruvates; Succinates; Triglycerides

Topics: Acetates; Acid-Base Equilibrium; Acidosis; Amino Acid Metabolism, Inborn Errors; Amino Acids; Blood Chemical Analysis; Butyrates; Child; Citrates; Fumarates; Humans; Infant; Malates; Poisoning; Pyruvates; Renal Aminoacidurias; Salicylates; Succinates; Toxicology; Urine

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Cysteamine; Fumarates; Ketosis; Maleates; Mercaptoethylamines