Reciprocal Interference of CPT I and GPAT

In preliminary studies unpublished data , we defined that a correct incubation medium intended for mitochondrial fatty acid oxidation should present a acyl-CoA albumin ratio lower than 1.5. Indeed, the radioactivity of acid-soluble products released during mitochondrial oxidation of 1-14C or 10-14C oleoyl-CoA was comparable for all ratios assayed below 1.5. Higher ratios gave rise to less labelled acid-soluble products from 10-l4C oleoyl-CoA, because P-oxidation was interrupted likely after...

Concluding Remarks Dry

Our understanding of the P-oxidation of unsaturated fatty acyl-CoA esters has expanded rapidly during the last few years. It is now clear that both mitochondria and peroxisomes in mammals have the complete enzymatic machinery to P-oxidise unsaturated fatty acids at rates dependent on the chain length of the fatty acids and the number and configuration of the double bonds. Most unsaturated fatty acids are oxidized in peroxisomes faster than their saturated counterparts, with the exception being...

Ketogenesis Versus Ketolysis

The process of converting fatty acids to ketone bodies is called ketogenesis whilst the process of exploiting such ketone bodies is variously described as ketolysis or ketone body utilisation. The situation described in Fig. 1a is presumably not tolerable in a single cell procaryote whose sole fuel source is fatty acids. However, in a hypothetical symbiotic 2-cell-type eukaryotic system Fig. 1b , carbon skeletons could still be conserved provided that, a ketogenic cell-type produces ketone...

Glucocorticoids and Fat Mobilisation a Response to Stress

We can more easily understand the logic of the synergistic interactions of the GR and PPAR RXR signal pathways on mHS gene expression, when we realise that one of the functions of glucocorticoid release into the blood is in the response of starvation stress.21 Starvation partly parallels the situations of the suckling neonate or the adult on a high fat low carbohydrate diet in that all three situations result in elevated plasma free fatty acid concentrations.22,23 In the case of starvation,...

Glucocorticoid Action on mHS Gene Transcription Initiation

The increases in mHS mRNA observed in response to glucocorticoids are likely to occur as a result of their direct action on the rate of transcription initiation of the mHS gene, since glucocorticoid response elements GREs that bind the glucocorticoid receptor GR have been identified in the mHS gene promoter Fig. 4 .17 In addition, glucocorticoids may act indirectly on mHS gene expression via the PPARa RXRa heterodimer, since the promoter regions of the genes encoding PPARa and RXRa also contain...

Confocal Laser Scanning Microscopy Of Human Skin Fibroblasts Showing Transient

F. R. van der Leij , H. Roelofsen1, K. E. Niezen-Koning, E. A. A. Nollen2, and J. R. G. Kuipers Department of Pediatrics department of Internal Medicine Department of Radiobiology Groningen Utrecht Institute for Drug Exploration Groningen University, Groningen The Netherlands The mitochondrial outer membrane enzyme carnitine palmitoyltransferase 1 CPT1 is a main site of regulation of intracellular long-chain fatty acid transport. At least two isoforms of CPT1 are expressed in the body L-CPT1...

Info Vlr

When 2-Bromopalniitoyl-C'oA was preincubated with mitochondria in the presence of 0.5 mM .-carnitine, inhibition was 100 in all cases. 'I' lt 0.001 compared to control. Student's Mest When 2-Bromopalniitoyl-C'oA was preincubated with mitochondria in the presence of 0.5 mM .-carnitine, inhibition was 100 in all cases. 'I' lt 0.001 compared to control. Student's Mest inhibitory effects of succinyl-CoA and methylmalonyl-CoA were likewise reduced as a result of Nagarse treatment. However, Nagarse...

Recent Studies on the Possible Identity of Microsomal CATa

Although CATA can be solubilized from rat liver microsomes using mild detergents such as deoxycholate5 and reconstituted into liposomes of known phospholipid compo-sition10 without loss of activity, further purification of the enzyme away from other membrane components requires harsher conditions, which inactivate the enzyme. For example, substantial further purification can be achieved by extraction into 8mM CHAPS with 4 M urea followed by anion-exchange chromatography and gel filtration N. M....

References Alb

1. Saggerson, E.D. 1982 Biochem. J. 202, 397-405. Carnitine acyltransferase activities in rat liver and heart measured with palmitoyl-CoA and octanoyl-CoA Latency, effects of K , bivalent metal ions and malonyl-CoA. 2. Kolodziej, M.P., PJ. Crilly, C.G. Corstorphine amp V.A. Zammit 1992 Biochem. J. 282, 415-421. Development and characterization of a polyclonal antibody against rat liver mitochondrial overt carnitine palmitoyltransferase CPT I Distinction of CPT I from CPT II and of isoforms of...

Info Udm

The values given are means sd for n 2- 4 The values given are means sd for n 2- 4 initial binding of the inhibitor to the site. Further, the acetyl analogue does not inhibit in CPT-II. As described above, increased acyl chain length contributes strongly to the affinity of both inhibitors and substrates for CPT-II. These kinetic studies suggest that it may indeed be possible to inhibit P-oxidation with minimal effect on the lipid recycling reactions in the rest of the cell.

Preface

In September 1991, Victor Zammit and I were in the Department of Biochemistry, the University of Cambridge, discussing our collaborative research project when we realized the potential value and need for a conference specifically concerned with fatty acid oxidation and ketogenesis. The idea, once seeded, was indulged and flourished into the first Fatty Acid Oxidation amp Ketogenesis FAOx amp K Conference that was held in the Department at Eastertime, 1992. It was attended by colleagues mainly...

Contents

Cambridge, Colleagues, Carnitine and Ketogenesis xv 1. Biogenesis of the Rat Liver Mitochondrial Carnitine Palmitoyltransferase I 1 Isabelle Cohen, Jean Girard, and Carina Prip-Buus 2. Subcellular Distribution of Mitochondrial Carnitine Palmitoyltransferase I in Rat Liver Evidence for a Distinctive N-Terminal Structure of the Microsomal but Not the Peroxisomal Enzyme 17 Fiona Fraser, Clark G. Corstorphine, and Victor A. Zammit 3. Topology of Hepatic Mitochondrial Carnitine Palmitoyltransferase...

References

1. McGarry, J.D., Woeltje, K.F., Kuwajima, M. amp Foster, D.W. 1989 Diabetes Metab. Rev., 5, 271-284. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. 2. Eaton, S., Bartlett, K. amp Pourfarzam, M. 1996 Biochem. J., 320, 345-357. Mammalian mitochondrial beta-oxidation. 3. McGarry, J.D. amp Brown, N.F. 1997 Eur. J. Biochem., 244, 1-14. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. 4. Park, E.A. amp Cook, G.A. 1998 Mol....