Vitamin C is accumulated in mammalian cells by two types of proteins: sodium-ascorbate co-transporters (SVCTs) and hexose transporters (GLUTs); in particular, SVCTs actively import ascorbate, the reduced form of this vitamin. SVCTs are surface glycoproteins encoded by two different genes, very similar in structure. They show distinct tissue distribution and functional characteristics, which indicate different physiological roles. SVCT1 is involved in whole-body homeostasis of vitamin C, while SVCT2 protects metabolically active cells against oxidative stress. Regulation at mRNA or protein level may serve for preferential accumulation of ascorbic acid at sites where it is needed. This review will summarize the present knowledge on structure, function and regulation of the SVCT transporters. Understanding the physiological role of SVCT1 and SVCT2 may lead to develop new therapeutic strategies to control intracellular vitamin C content or to promote tissue-specific delivery of vitamin C-drug conjugates.

SVCT1 and SVCT2: key proteins for vitamin C uptake

Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of i...

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Panorganismal Gut Microbiome−Host Metabolic Crosstalk

Vitamin C for the treatment of sepsis: The scientific rationale.

The sodium-dependent ascorbic acid transporter family SLC23.

This review summarizes knowledge concerning a ubiquitous plasma transmembrane protein family that mediates nucleobase or ascorbate secondary active transport (NAT). We show that prototype bacterial and mostly fungal members have become unique model systems to unravel structure-function relationships and regulation of expression, using classical and reverse genetics, as well as biochemical approaches. We discuss the importance of NAT-mediated ascorbate transport in mammals and how changes in substrate specificity, from different nucleobases to ascorbate, might have evolved at the molecular level. Finally, we also discuss how modelling NAT-purine interactions might constitute a step towards the use of NAT proteins as specific gateways for targeting pathogenic microbes.

The nucleobase–ascorbate transporter (NAT) family: genomics, evolution, structure–function relationships and physiological role

The adrenal gland is among the organs with the highest concentration of vitamin C in the body. Interestingly, both the adrenal cortex and the medulla accumulate such high levels of ascorbate. Ascorbic acid is a cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis. Here we provide an overview on the role of vitamin C in the adrenal cortex and medulla derived from in vitro and in vivo studies. In addition, recent insights gained from an animal model with a deletion in the gene for the ascorbic acid transporter will be summarized. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die soon after birth. There is a significant decrease of tissue catecholamine levels in the adrenals. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice show depletion of catecholamine storage vesicles, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone and altered morphology of mitochondrial membranes indicate additional effects of the deficiency on adrenal cortical function. The data derived from these animal models and various cell culture studies confirm a crucial role for vitamin C for both the adrenal cortex as well as the adrenal medulla further underlining the interdependence of the two endocrine systems united in one gland.

P. Patak

Papers

Vitamin C Is an Important Cofactor for Both Adrenal Cortex and Adrenal Medulla