MCAT Biochemistry Review
Chapter 9: Carbohydrate Metabolism I: Glycolysis, Glycogen, Gluconeogenesis, and the Pentose Phosphate Pathway
9.3 Other Monosaccharides
While glucose represents the primary monosaccharide used by cells, other monosaccharides such as galactose and fructose can also contribute to ATP production by feeding into glycolysis or other metabolic processes. These monosaccharides are tested far less frequently than glucose on the MCAT, but are included here to compare and contrast their metabolism with glycolysis. In particular, notice the similarities between Figure 9.2 (glycolysis) and Figures 9.4 (galactose metabolism) and 9.5 (fructose metabolism).
Figure 9.4. Galactose Metabolism
Primary lactose intolerance is caused by a hereditary deficiency of lactase. Secondary lactose intolerance can be precipitated at any age by gastrointestinal disturbances that cause damage to the intestinal lining, where lactase is found.
Common symptoms of lactose intolerance include vomiting, bloating, explosive and watery diarrhea, cramps, and dehydration. The symptoms can be attributed to bacterial fermentation of lactose, which produces a mixture of CH4, H2, and small organic acids. The acids are osmotically active and result in the movement of water into the intestinal lumen.
An important source of galactose in the diet is the disaccharide lactose present in milk. Lactose is hydrolyzed to galactose and glucose by lactase, which is a brush-border enzyme of the duodenum. Along with other monosaccharides, galactose reaches the liver through the hepatic portal vein. Once transported into tissues, galactose is phosphorylated by galactokinase, trapping it in the cell. The resulting galactose 1-phosphate is converted to glucose 1-phosphate by galactose-1-phosphate uridyltransferase and an epimerase. Epimerases are enzymes that catalyze the conversion of one sugar epimer to another; remember from Chapter 4 of MCAT Biochemistry Review that epimers are diastereomers that differ at exactly one chiral carbon. The pathway is shown in Figure 9.4; important enzymes to remember are:
· Galactose-1-phosphate uridyltransferase
Genetic deficiencies of galactokinase or galactose-1-phosphate uridyltransferase lead to galactosemia. Cataracts are a characteristic finding, which result from the conversion of excess galactose in the blood to galactitol in the lens of the eye by aldose reductase. Galactitol is a polyol (a carbon chain with many alcohol groups) and, as such, is hydrophilic. Accumulation of galactitol in the lens causes osmotic damage and cataracts.
Deficiency of galactose-1-phosphate uridyltransferase is more severe because, in addition to causing galactosemia, it leads to galactose 1-phosphate getting stuck intracellularly in the liver, brain, and other tissues and not diffusing out.
Fructose is found in honey and fruit and as part of the disaccharide sucrose (common table sugar). Sucrose is hydrolyzed by the duodenal brush-border enzyme sucrase, and the resulting monosaccharides, glucose and fructose, are absorbed into the hepatic portal vein. The liver phosphorylates fructose using fructokinase to trap it in the cell. The resulting fructose 1-phosphate is then cleaved into glyceraldehyde and DHAP by aldolase B. Smaller amounts are metabolized in renal proximal tubules. The pathway is shown in Figure 9.5.
Figure 9.5. Fructose Metabolism
Because dihydroxyacetone phosphate (DHAP) and glyceraldehyde, the products of fructose metabolism, are downstream from the key regulatory and rate-limiting enzyme of glycolysis (PFK-1), a high-fructose drink supplies a quick source of energy in both aerobic and anaerobic cells.
MCAT Concept Check 9.3:
Before you move on, assess your understanding of the material with these questions.
1. Which enzyme is responsible for trapping galactose in the cell? What enzyme in galactose metabolism results in a product that can feed directly into glycolysis, linking the two pathways?
· “Trapping” enzyme:
· “Linking” enzyme:
2. Which enzyme is responsible for trapping fructose in the cell? What enzyme in fructose metabolism results in a product that can feed directly into glycolysis, linking the two pathways?
· “Trapping” enzyme:
· “Linking” enzyme: