Carnitine transporter

Lahjouji, K., G. A. Mitchell, and I. A. Qureshi. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol. Genet. Metab. 2001, 73, 287-297. 

Tamai, I., et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J. Biol. Chem. 1998, 273, 20378-20382. 

Ohashi, R., et al. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2) its pharmacological and toxicological relevance. J. Pharmacol. Exp. Ther. 1999, 292, 778-784. 

Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nature Genet 1999 21(1) 91 94. 

Lamhonwah AM, Tein I. Carnitine uptake defect frameshift mutations in the human plasmalemmal carnitine transporter gene. Biochem Biophys Res Commun 1998 252(2) 396-401. 

Wang Y, Kelly MA, Cowan TM, Fongo N. A missense mutation in the OCTN2 gene associated with residual carnitine transport activity. Hum Mutat 2000 ... 

Ganapathy ME, Huang W, Raj an DP, Carter AL, Sugawara M, Iseki K et al. /1-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000 275(3) 1699 1707. 

Tamai I, China K, Sai Y, Kobayashi D, Nezu J, Kawahara E et al. Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its sub-cellular localization in kidney. Biochim Biophys Acta 2001 1512(2) 273-284. 

Tang NL, Ganapathy V, Wu X, Hui J, Seth P, Yuen PM et al. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet 1999 8(4) 655-660. 

The genetically determined defect of membrane carnitine transport is the only known condition that fulfills the criteria for primary carnitine deficiency [4, 9]. This condition, like the other conditions involving the carnitine cycle, is not associated with dicarboxylic aciduria. It is... 

Defects of mitochondrial transport interfere with the movement of molecules across the inner mitochondrial membrane, which is tightly regulated by specific translocation systems. The carnitine cycle is shown in Figure 42-2 and is responsible for the translocation of acyl-CoA thioesters from the cytosol into the mitochondrial matrix. The carnitine cycle involves four elements the plasma membrane carnitine transporter system, CPT I, the carnitine-acyl carnitine translocase system in the inner mitochondrial membrane and CPT II. Genetic defects have been described for each of these four steps, as discussed previously [4,8,9]. 

Tein, I. Carnitine transport pathophysiology and metabolism of known molecular defects. /. Inker. Metab. Dis. 26 147-169, 2003... 

Y. Kato, M. Sugiura, T. Sugiura, T. Wakayama, Y. Kubo, D. Kobayashi, Y. Sai, I. Tamai, S. Iseki, and A. Tsuji. Organic cation/camitine transporter octn2 (slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Mol Pharmacol 70 829-837 (2006). 

J. Nezu, I. Tamai, A. Oku, R. Ohashi, H. Yabuuchi, N. Hashimoto, H. Nikaido, Y. Sai, A. Koizumi, Y. Shoji, G. Takada, T. Matsuishi, M. Yoshino, H. Kato, T. Ohura, G. Tsujimoto, J. Hayakawa, M. Shimane, and A. Tsuji. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 21 91-94 (1999). 

Carnitine acyltransfefase-I (CAT-1) and carnitine acyltran erase-2 (CAT-2) are also refened to as carnitine palmrtoyl transferase-1 (CPT-1) and carnitine palmitoyl transferase-2 (CPT-2). The carnitine transport system is most important for allowing long-chain fatty acids to enter into the mitochondria. 

Children with a primary deficiency of the carnitine transporter present with acute episodes of hypoglycaemia leading to loss of consciousness during even a short fast. (See Chapter 9 for a role of carnitine) in the Krebs cycle. 

Figure 7.15 The interaction between valproate and the mitochondrial p-oxidation system. Dark arrows denote depletion. Filled in circle is the carnitine transporter. 2,4, VPA 2,4, diene-VPA CoA ester. This reactive metabolite damages the enzyme enoyl CoA hydratase and the mitochondrial membranes and depletes GSH, as indicated.

FIGURE17-6 Fatty acid entry into mitochondria via the acyl-carnitine/ carnitine transporter. After fatty acyl-carnitine is formed at the outer membrane or in the intermembrane space, it moves into the matrix by facilitated diffusion through the transporter in the inner membrane. In the matrix, the acyl group istransferred to mitochondrial coenzyme... 

As many as 1 in 10,000 persons may inherit such prob-lems.48 50a Tire proteins that may be defective include a plasma membrane carnitine transporter carnitine palmitoyltransferases camitine/acylcamitine trans-locase long-chain, medium-chain, and short-chain acyl-CoA dehydrogenases 2,4-dienoyl-CoA reductase (Eq. 17-1) and long-chain 3-hydroxyacyl-CoA dehydrogenase. Some of these are indicated in Fig. 17-2. 

Figure 17-2 Some specific defects in proteins of P oxidation and acyl-carnitine transport causing cardiomyopathy are indicated by the green asterisks. CPT I and CPT II are carnitine palmitoyltransferases I and II. After Kelly and Strauss.48...

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