Glucose sodium coupled

Historically important as an example of flux coupling, and one that was investigated in detail becoming a paradigm for coupled transport, was the sodium coupled glucose transport system of the small intestine and kidney (see below). This was a symport (or co-transport) rather than an antiport, normally carrying glucose into the cell coupled to a flow of sodium ions in the same direction. 

Uglem, G. L. Prior, D. J. (1980). Hymenolepis diminuta chloride fluxes and membrane potentials associated with sodium-coupled glucose transport. Experimental Parasitology, 50 287-94. 

Figure 3 Model of the sodium-coupled glucose cotransporter. Binding site for both sodium and glucose is alternatively exposed at opposite membrane surfaces. [Adapted from Silvennan (4).]...

A glycoalkaloid, nervosine, C36H53O12N, was isolated as its picrate (mp 131° [a] -I-12.8° as hydrochloride). Alkaline hydrolysis generated lindelofidine (d-isoretronecanol) and an acid which on hydrolysis with acid generated D-glucose and L-arabinose. The disaccharide obtained on mild hydrolysis was reduced with sodium borohydride and then hydrolyzed further. There was obtained arabinose, indicating that the aldehyde function of the glucose is coupled with the phenolic hydroxyl of the acid moiety. Exhaustive spectral analysis of the latter as well as of its tetrahydro derivative show that nervosine is LXXXIV 132). 

The first synthesis, by method a, of amylostatin (XG) was reported by Kuzuhara and Sakairi. The synthon for the cyclohexene moiety was the benzylated allyl bromide 382, derived from D-glucose by the sequence 378 — 382 of the Perrier reaction. The coupling reaction of 382 using an excess of 4-amino-T,6 -anhydro-4,6-dideoxymaltose tetrabenzyl ether (383), and sodium iodide in DMF for 3 days produced a mixture of the epimeric monocarba-trisaccharide derivatives, separation of which gave the protected derivatives in 15% yield. 

The model nicely explained this experimental finding, but at this early stage was really no more than a working hypothesis, and was only one of a number of plausible possibilities. For example, coupling glucose influx to potassium efflux rather than sodium influx would have explained the data adequately. However, as Crane and his colleagues went on to demonstrate with a series of well designed experiments, the fundamental idea of what became known as the Crane hypothesis remained plausible while other obvious hypotheses were excluded (Crane, 1975). 

Oral rehydration therapy (ORT) with glucose-electrolyte solution is sufficient to treat the vast majority of episodes of watery diarrhoea from acute gastroenteritis. As a simple, effective, cheap and readily administered therapy for a potentially lethal condition, ORT must rank as a major advance in therapy. It is effective because glucose-coupled sodium transport continues during diarrhoea and so enhances replacement of water and electrolyte losses in the stool. 

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