Aldose reductase + Sorbitol + Galactitol

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A post for sorbitol + galactitol? What the fuck? Yeah, I know. A bit odd. But it’s up to you whether you want to know the HY points or not.

High plasma glucose levels (i.e., in diabetes mellitus) = high intracellular sorbitol levels.

This is because aldose reductase is an intracellular enzyme that converts glucose to sorbitol.

Sorbitol can then cause osmotic injury to cells because it leads to greater intracellular retention of water relative to glucose, thereby causing cellular swelling.

If a USMLE question asks you how cataracts or neuropathy occurs in diabetes, osmotic injury to cells is the answer.

In contrast, the nephropathy, retinopathy, and atherosclerosis seen in diabetes are due to non-enzymatic glycosylation of endothelial cells by glucose, which leads to direct cellular damage.

Non-enzymatic glycosylation of endothelial cells = endothelial damage + ↑ permeability → atherosclerosis, diabetic nephropathy, retinopathy

Sorbitol accumulation in cells due to aldose reductase → cellular swelling / osmotic damage → cataracts, neuropathy

All you need to know about galactitol is:

Galactose, via aldose reductase, → galactitol.

Aldose reductase converts:

Glucose → sorbitol

Galactose → galactitol

So who the fuck cares? It’s because the cataracts in galactose disorders are due to galactitol, not sorbitol.

So the USMLE will tell you there’s an infant with cataracts + reducing sugars in the urine (galactokinase deficiency), or cataracts + hepatomegaly + jaundice (classic galactosemia), and then they’ll ask which enzyme is responsible for the cataracts, and you simply select aldose reductase.

And of course if they ask for the product of the reaction, you just select galactitol, not sorbitol.

Nothing dramatic. Short post. But HY information nevertheless.

1. Which of the following occur(s) due to non-enzymatic glycosylation of endothelial cells? (Select all that apply)

 
 
 
 
 

2. Which of the following occur(s) due to the effects of intracellular sorbitol ? (Select all that apply)

 
 
 
 
 

3. 6-month old with slowly developing cataracts. There are reducing sugars detected in the urine. What enzyme is responsible for the development of his cataracts?

 
 
 

4. In the conversion of glucose to sorbitol, which of the following is a required cofactor?