Introduction

The carnitine acyltransferases (CPT) catalyze the reversible acyl group transfer between the CoA and carnitine pools (reviewed in).1,2 Only carnitine acetyltransferase (CAT), the soluble peroxisomal COT and the mitochondrial inner carnitine palmitoyltransferase (CPT-II) are not regulated allosterically. The mitochondrial outer carnitine palmitoyltransferase (CPT-I), the peroxisomal overt carnitine octanoyltransferase (COT), and the enzyme in the endoplasmic reticulum (CPTER) are all inhibited by physiological concentrations of malonyl-CoA, the precursor for fatty acid synthesis.3-5 CPT levels and the IC50 levels for malonyl-CoA inhibition change with metabolic and hormonal status. For example, fasting increases CPT levels and decreases sensitivity to malonyl-CoA.5,6 Insulin inhibits CPT activity but glucagon increases it.7 Hormonally induced changes in CPT-I correlate with changes in fatty acid oxidation, in accord with the role of CPT-I in the regulation of the entry of fatty acyl groups into mitochondria. Hypolipodemic drugs, such as 2-tetradecylglycidic acid (TDGA) and etomoxir, inhibit CPT-I and, hence, decrease fatty acid oxidation and ketogenesis.8,9

However, not just CPT-I, but all CPT enzymes that use cytoplasmic substrates are regulated by malonyl-CoA and inhibited by TDGA and etomoxir. -12 Thus, these drugs will also interfere with peroxisomal oxidation and influence microsomal acyl-CoA utilizing pathways such as lipid synthesis and lipid modification of proteins for export. In view of recent indications that non-mitochondrial acyl-CoA pools may influence membrane turnover,13 this may not be desirable, so inhibitors specific to CPT-I would be better. We have studied the kinetics and inhibition of two of the CPT family of enzymes as the first step towards finding differences that could be exploited to inhibit (J-oxidation without affecting peripheral function.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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