Propionyl carnitine

D acquarica, I., Gasparrini, F., Giannoli, B., Badaloni, E., Galletti, B., Giorgi, F., Tinti, M.O., Vigevani, A. (2004). Enantio- and chemo-selective HPLC separations hy chiral-achiral tandem-columns approach the combination of CHIROBIOTIC TAG and SCX for the analysis of propionyl carnitine and related impurities. J. Chromatogr. A 1061, 167-173. 

Brevetti G, Pema S, Sabba C, Rossini A, Scotto di Uccio V, Berardi E, Godi L. Superiority of L-propionyl carnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease An acute, intravenous, double-blind, cross-over study. Eur Heart J 1992 13 251-255. 

A new chiral-achiral tandem-columns arrangement based on a commercially available TAG CSP connected in series with a Spherisorb S5 SCX column was developed for the enantio- and chemoselective dosage of propionyl L-carnitine and relative impurities in pharmaceutical batches [166]. Some chromatograms relative to the separation of carnitine and carnitine derivatives on a teicoplanin CSP are collected in Figure 2.18. 

Fatty acids with an odd number of C atoms are treated in the same way as normal fatty acids—i. e., they are taken up by the cell with ATP-dependent activation to acyl CoA and are transported into the mitochondria with the help of the carnitine shuttle and broken down there by p-oxidation (see p. 164). In the last step, propionyl CoA arises instead of acetyl CoA. This is first carboxylated by propionyl CoA carboxylase into fSj-methylmalonyl CoA [3], which—after isomerization into the (i ) enantiomer (not shown see p. 411)—is isomerized into succinyl CoA [4]. 

Propionyl-L-Carnitine HCI Tablet injection Chronic congestive heart failure... 

Roe CR, Millington DS, Maltby DA, Bohan TP, Hoppel CL (1984) L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. J Clin Invest 73 1785-1788... 

Jakobs BS, Wanders RJ (1995) Fatty acid beta-oxidation in peroxisomes and mitochondria the first, unequivocal evidence for the involvement of carnitine in shuttling propionyl-CoA from peroxisomes to mitochondria. Biochem Biophys Res Commun 213 1035-1041... 

Orally administered L-carnitine and propionyl-L-carnitine may have metabolic benefits by providing an additional source of carnitine to buffer the cellular acyl CoA pool. In this way, carnitine may enhance glucose oxidation under ischemic conditions and improve energy metabolism in the ischemic skeletal muscle. Propionyl-CoA generated from propionyl-L-carnitine may also improve oxidative metabolism through its anaphoretic actions in priming the Kreb s cycle, secondary to succinyl-CoA production. 

After 180 days of treatment there was a significant improvement of 73 9% (mean SE) in maximal walking distance in PAD patients treated with propionyl-L-carnitine compared to placebo (80). Propionyl-L-camitine has been shown to improve treadmill performance and quality of life in patients with claudication. After six months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 222 seconds (a 54% increase) as compared with an improvement of 75 191 seconds (a 25% increase) for those on placebo (p < 0.001) (81). 

Sethi, R., Wang, X., Ferrari, R., and Dhalla, N.S. 2004. Improvement of cardiac function and P-adrenergic signal transduction by propionyl L-carnitine in congestive heart failure due to myocardial infarction. Coron. Artery Dis. 15 65-71. 

As a result of the reduced activity of the mutase in vitamin B12 deficiency, there is an accumulation of methyhnalonyl CoA, some of which is hydrolyzed to yield methylmalonic acid, which is excreted in the urine. As discussed in Section 10.10.3, this can be exploited as a means of assessing vitamin B12 nutritional status. There may also be some general metabolic acidosis, which has been attributed to depletion of CoA because of the accumulation of methyl-malonyl CoA. However, vitamin B12 deficiency seems to result in increased synthesis of CoA to maintain normal pools of metabolically useable coenzyme. Unlike coenzyme A and acetyl CoA, neither methylmalonyl CoA nor propionyl CoA (which also accumulates in vitamin B12 deficiency) inhibits pantothenate kinase (Section 12.2.1). Thus, as CoA is sequestered in these metabolic intermediates, there is relief of feedback inhibition of its de novo synthesis. At the same time, CoA may be spared by the formation of short-chain fatty acyl carnitine derivatives (Section 14.1.1), which are excreted in increased amounts in vitamin B12 deficiency. In vitamin Bi2-deficient rats, the urinary excretion of acyl carnitine increases from 10 to 11 nmol per day to 120nmolper day (Brass etal., 1990). 

Trade names Acetyl-L-carnitine Aplegin B(t)Factor Carnitine Carnitor L-Carnipure Levocarnitine Propionyl-L-carnitine Vitacarn Vitamin BM... 

L-camitine Acetyl-L-carnitine, Aplegin, B(t)Factor, Carnitine, Carnitor, L-Carnipure, Levocarnitine, Propionyl-L-... 

Many fatty acids have structures that require variations of this basic pattern. Long-chain fatty acids that are unsaturated fatty acids generally require additional isomerization and oxidation-reduction reactions to rearrange their double bonds during p-oxidation. Metabolism of water-soluble medium-chain-length fatty acids does not require carnitine and occurs only in liver. Odd-chain-length fatty acids undergo p-oxidation to the terminal three-carbon propionyl CoA, which enters the TCA cycle as succinyl CoA. 

Fig. 23.15. Oxidation of phytanic acid. A peroxisomal a-hydroxylase oxidizes the a-car-bon, and its subsequent oxidation to a carboxyl group releases the carboxyl carbon as CO2. Subsequent spirals of peroxisomal p-oxidation alternately release propionyl and acetyl CoA. At a chain length of approximately 8 carbons, the remaining branched fatty acid is transferred to mitochondria as a medium-chain carnitine derivative.

Propionyl-7-carnitine Carnitine, 0-propanoyl C10H49NO4 20064-19-1 217.263 hyg pr(2-PrOH) 147 dec ... 

Figure I. Acyl-carnitine profiles in fatly acid uxidatiun defects. Acyl-carnitine profiles were obtained from plasma or serum samples as described in materials and methods. In the upper left panel normal control the positions of the deutcrated internal standards (IS) arc indicated. For comparison the profiles were printed with the - Hj-CS-IS at SO iiof full scale in all panels, The ion at m/z 218 corresponds to free carnitine m/z 260, acetyl-carnitine nifz 274, propionyl-carniline m/z 288, butyryl-carnitine m/z 302, iso-C5-carnitinc (isovalcryl-carnitine) m/z 316, hexanoyI-carnitine m/z. 344, octanoyl-carnitine m/z 370, C 10 1-carnitine m/z 400, C12-camitinc m/z 426. CT 4 1-carnitine m/z 444, hydroxy-C 14-carmtine m/z 4,36, Cl 6-carnitine m/z 472, hydroxy-C16-carnitine m/z 482, Cl8 1-carnitine m/z 498, hydroxy-C 18 1-carnitine.

A secondary carnitine deficiency due to accumulation of propionyl-CoA and increased concentration of acylcamitines is also common [13]. Superficial desquamation, alopecia, and corneal ulcerations similar to staphylococcal scalded skin syndrome or acrodermatitis enteropathica-like syndrome, typically associated with diarrhea, may be seen secondary to acute protein malnutrition or essential amino acid deficiency, especially isoleucine deficiency [34, 52-54]. Immune dysfunction has also been suggested with an increased risk for viral or bacterial infections, but good studies are lacking [34]. Chronic moniliasis has been described and reflects the effect of propionyl-CoA and methylmalonate on T-cell number and function [7], Finally, acute and chronic pancreatitis, osteopenia or osteoporosis, and ovarian failure may also occur the etiologies of which remain unclear [3, 7, 24, 34, 36,47, 55-59],... 

Reference values for the acylcarnitines are derived from >500 patients, mostly pediatric (0.2-16 yrs), evaluated for metabolic disorders in the author s laboratory but with no manifest biochemical evidence of disease. Individuals with any markedly abnormal values were discounted. The analytical method used was tandem mass spectrometry with electrospray ionization. Internal standards used were stable isotope-labeled analogs of acetyl, propionyl, butyryl, octanoyl and palmitoyl carnitine. The values for straight-chain C2, C3, C4, C5, C6, C8, CIO, C14, C16 and Cl8 1 species are in pmol/1 and are derived from calibration curves using analytical standards all other values are ratios of the signal for the compound to an appropriate internal standard. All values are mean + 2 std. dev. except where a range is given... 

---