4.2.1 Genetic defects in lactose metabolism
A deficiency of the brush border enzyme lactase gives rise to a condition named lactose intolerance, found frequently in people of East Asian descent past their infant age. If lactose is not cleaved, it cannot be absorbed, so it makes its way down the drain from the small into the large intestine. Many of the bacteria found there have the capacity to metabolize lactose, which they convert to acids and gas1. This leads to abdominal discomfort and diarrhea. Since the environment in the large intestine lacks oxygen, hydrogen (H2) generated in the bacterial fermentation is not oxidized but instead released as such, and in part is exhaled (Figure 4.2.1-1). An increase in exhaled hydrogen upon ingestion of lactose can be used to diagnose the condition. Treatment consists in omission of lactose in the diet. Milk can be pre-treated with purified bacterial β-galactosidase, rendering it suitable for consumption by lactose-intolerant individuals. Fermented milk products such as yoghurt and cheese are depleted of lactose by bacterial fermentation and therefore do not pose a problem for lactose-intolerant individuals.
Other metabolic defects resemble those occurring in fructose metabolism. Two different enzyme defects are known; somewhat confusingly, they are both referred to as galactosemia, which means 'galactose in the blood'.
- A defect of galactokinase. In this case, galactose is simply not metabolized at all; it builds up in the blood and will mostly be eliminated in the urine. The liver will not be affected; however, there is a complication elsewhere: Cataract (cloudiness of the lens of the eye). This is believed to occur by reduction of galactose to galactitol by aldose reductase (see below).
- A defect of galactose-1-phosphate uridyltransferase. In this case, the situation resembles that outlined above for fructose intolerance: ATP is depleted in the liver cells, because phosphate is trapped in galactose-1-phosphate, and severe liver damage results.
1: Escherichia coli for example performs a 'mixed acid fermentation'. One of the products of this fermentation is formic acid (HCOOH), which is then cleaved by formic acid lyase to H2 and CO2. The cleavage of formic acid serves the same purpose, namely detoxification of excess acid, as does ethanolic fermentation in yeast.