Biomedical subjects

B Garavaglia

Publications and source records attributed to B Garavaglia.

41 records · Page 3Linked to original sources

PubMed1988

Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria.

L-carnitine stimulated CO2 production from 1-14C pyruvate in mitochondria from human skeletal muscle nearly twofold. A comparable increase in the pyruvate dehydrogenase complex (PDHC) activity was seen. Moreover, in the presence of L-carnitine and at pyruvate concentration greater than 0.25 mM, this effect was associated with a marked increase of acetylcarnitine synthesis. Deoxycarnitine, an inhibitor of carnitine acetyltransferase (CAT), partially reversed the effect of carnitine on PDHC activity. The stimulatory effect of carnitine on PDHC activity in human mitochondria is mediated by the modulation of the intramitochondrial acetyl-CoA/CoASH ratio.

Acetyl Coenzyme A↗

PubMed1988

Multisystem triglyceride storage disease is due to a specific defect in the degradation of endocellularly synthesized triglycerides.

We studied two unrelated patients with autosomal recessive multisystem triglyceride storage disease. Cultured fibroblasts accumulated 10 times more triglyceride than controls under glycerol or palmitate feeding. Mutant fibroblasts could not degrade accumulated triglycerides of endogenous origin, but normally degraded endogenously synthesized phospholipids. When the cells were fed with exogenous olein, triglyceride catabolism was in the normal range. Oxidation of long-chain, medium-chain, and short-chain fatty acids was normal, and the activities of acidic, neutral, and alkaline lipase in cell extracts were normal. The disease seems to be due to a specific impairment in the degradation of triglycerides synthesized endogenously.

Cells, Cultured↗

PubMed1984

Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency.

Two patients with propionic acidemia (PA) and two patients with methylmalonic aciduria (MMA) had low plasma free carnitine and increased short-chain acylcarnitines. Urinary excretion of free carnitine was decreased, while the excretion of short-chain acylcarnitines, mostly propionylcarnitine , was increased. Carnitine supplementation markedly increased the short-chain acylcarnitine fractions of both plasma and urine. Total carnitine content was decreased in skeletal muscle biopsies obtained from two of the patients. It is suggested that in these organic acidurias mitochondrial propionylcarnitine , formed from free carnitine and excess propionylCoA exchanges with free cytosolic carnitine: propionylcarnitine is then lost in the urine, causing secondary carnitine deficiency in the tissues.

Carnitine↗

PubMed1984

Systemic carnitine deficiency: clinical, biochemical, and morphological cure with L-carnitine.

A 20-year-old woman had systemic carnitine deficiency. Biochemical studies of cultured fibroblasts, skeletal muscle mitochondria, and fluids showed no evidence of other disease that might deplete tissue carnitine stores. Carnitine supplementation produced a dramatic improvement in her clinical condition: she gained weight and strength and recovered brain function, which had deteriorated slightly after repeated episodes of encephalopathy. Lipid droplets disappeared from skeletal muscle and plasma, and muscle carnitine content rose from low to normal values. On treatment, she excreted less carnitine than controls. This form of systemic carnitine deficiency may be due to defective carnitine biosynthesis.

Acids↗

PubMedDate not supplied

Phenotype and genotype variation in primary carnitine deficiency.

PURPOSE: Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation resulting from defective carnitine transport. This disease is caused by mutations in the carnitine transporter gene SLC22A5. The objective of this study was to extend mutational analysis to four additional families with this disorder and determine whether recurrent mutations could be found. METHODS: The SLC22A5 gene encoding the OCTN2 carnitine transporter was sequenced, and the missense mutations identified were expressed in Chinese hamster ovary (CHO) cells. RESULTS: DNA sequencing revealed four novel mutations (Y4X; dup 254-264, 133X; R19P; R399Q). Alleles introducing premature STOP codons reduced the levels of OCTN2 mRNA. Carnitine transport in CHO cells expressing the R19P and R399Q mutations was reduced to < 5% of normal. The 133X mutation was found in two unrelated European families. Two patients within the same family, both homozygous for the same mutation (R399Q) had completely different clinical presentation. CONCLUSIONS: Heterogeneous mutations in the SLC22A5 gene cause primary carnitine deficiency. Different presentations are observed even in children with identical mutations.

Animals↗