Glucose Transport and Transporters in the Endomembranes

Abstract

Glucose is a basic nutrient in most of the creatures; its transport through biological membranes is an absolute requirement of life. This role is fulfilled by glucose transporters, mediating the transport of glucose by facilitated diffusion or by secondary active transport. GLUT (glucose transporter) or SLC2A (Solute carrier 2A) families represent the main glucose transporters in mammalian cells, originally described as plasma membrane transporters. Glucose transport through intracellular membranes has not been elucidated yet; however, glucose is formed in the lumen of various organelles. The glucose-6-phosphatase system catalyzing the last common step of gluconeogenesis and glycogenolysis generates glucose within the lumen of the endoplasmic reticulum. Posttranslational processing of the oligosaccharide moiety of glycoproteins also results in intraluminal glucose formation in the endoplasmic reticulum (ER) and Golgi. Autophagic degradation of polysaccharides, glycoproteins, and glycolipids leads to glucose accumulation in lysosomes. Despite the obvious necessity, the mechanism of glucose transport and the molecular nature of mediating proteins in the endomembranes have been hardly elucidated for the last few years. However, recent studies revealed the intracellular localization and functional features of some glucose transporters; the aim of the present paper was to summarize the collected knowledge.

Keywords: GLUT; SGLT; endomembrane; glucose; transporter.

Figure 1

G6PC (glucose-6-phosphatase) is a transmembrane enzyme with the catalytic subunit facing the endoplasmic reticulum (ER) lumen. It drives the hydrolysis of glucose-6-phosphate (G6P) to glucose and inorganic phosphate (P_i). The enzyme compartmentation requires transporters for G6P, Pi, and glucose. The identity of Pi transporter has not been clarified yet. Three possible transport mechanisms may explain the exit of glucose from the ER: translocon pore, glucose transporter (GLUT) transporters in transit through the secretory pathway, or a yet unidentified glucose transporter.

Figure 2

Protein glycosylation/deglycosylation in the endoplasmic reticulum. Oligosaccharyl-transferases link glycan moiety to nascent polypeptide chains. In the further maturation steps, glucosidase I and II trim the terminal glucose from oligosaccharide residue, and the free glucose is carried out of the endoplasmic reticulum via yet un-identified transporters. ER, endoplasmic reticulum; OST, oligosaccharyl-transferases.

Figure 3

Sugar-containing macromolecules digested by lysosomal hydrolases. The resulting monosaccharides are exported from the autolysosomal lumen through possible sugar transporter Spin. Spin is also involved in autophagic lysosome reformation.