The Sodium/Multivitamin Transporter

Abstract

The Na+/multivitamin transporter (SMVT) is a member of the Solute:Sodium Symporter (SSS) family, that catalyzes the Na+-dependent uptake of the structurally diverse water-soluble vitamins pantothenic acid (vitamin B5) and biotin (vitamin H), α-lipoic acid – a vitamin-like substance with strong anti-oxidant properties – and iodide. The organic substrates of SMVT play central roles in the cellular metabolism and are, therefore, essential for normal human health and development. For example, biotin deficiency leads to growth retardation, dermatological disorders, and neurological disorders. Animal studies have shown that biotin deficiency during pregnancy is directly correlated to embryonic growth retardation, congenital malformation, and death of the embryo. This chapter focuses on the structural and functional features of the human isoform of SMVT (hSMVT) the discovery of which was greatly facilitated by the cloning and expression of hSMVT in tractable expression systems. Special emphasis will be given to mechanistic implications of the transport process of hSMVT that will inform our understanding of the molecular determinants of hSMVT-mediated transport in dynamic context to alleviate the development and optimization of hSMVT as a multipotent platform for drug delivery.

Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease

“…Whereas certain genetically-transmitted disorders causing defects in the CoA synthetic pathway occur in humans, the effects of chronic vitamin B5 depletion on the brain are poorly understood [68,69]. The human sodium-dependent multivitamin transporter (hSMVT), encoded by the SLC5A6 gene, mediates uptake of pantothenate along with biotin, lipoate, and iodide [70]. Human SMVT is the main transporter of pantothenate through the blood-brain barrier [71,72], and loss-of-function mutation in SLCA6 in humans causes brain dysfunction, amongst other phenotypic effects [73].…”

Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity

“…CoA and phosphopantetheine are converted to free pantothenic acid by endogenous enzymes such as phosphatase and pantetheinase in the small intestine. Free pantothenic acid is absorbed via sodium-dependent multivitamin transporter (SMVT) expressed on the epithelium of the small intestine and is then released into the blood (80). Finally, free pantothenic acid is converted back to CoA and distributed throughout the body, particularly to the liver and kidney.…”

Prokaryotic Solute/Sodium Symporters: Versatile Functions and Mechanisms of a Transporter Family

“…For example, mutations in genes of human sodium/glucose transporters (SGLTs) cause the rare diseases glucose-galactose malabsorption and familial renal glucosuria [ 28 ]. Substrates of the sodium/multivitamin transporter (SMVT) play central roles in the cellular metabolism, and transporter defects can lead to growth retardation, dermatological disorders, and neurological disorders [ 29 ]. The human sodium/iodide symporter (NIS) is required for hormone synthesis in the thyroid and used for diagnostics and therapy of thyroid cancer [ 30 ].…”