The glycolytic pathway begins with the simple sugar glucose and leads to pyruvate and eventually the Kreb's cycle. Dietary carbohydrates include a variety of sugars that are funneled into glycolysis to supply energy, including other monosaccharides, disaccharides, and polysaccharides like starch. Fructose is an abundant monosaccharide in fruit, and is also found along with glucose in the common disaccharide sucrose. Fructose enters glycolysis by different pathways in the liver and muscle. In muscle, fructose is a substrate of hexokinase, like glucose, and enters the pathway directly as fructose 6-phosphate. In liver, hexokinase is present in very low levels and fructose passes through a more complex pathway. Fructose is first phosphorylated to form fructose 1-phosphate, which is then split into glyceraldehyde and dihydroxyacetone phosphate to enter glycolysis as glyceraldehyde 3-phosphate. The sugar mannose also enters glycolysis at this point, first being converted to mannose 6-phosphate that is then isomerized to produce fructose 6-phosphate. Lactose is a disaccharide found in milk, and is composed of glucose and galactose. Galactose only differs from glucose in its stereochemistry at one position, but must be converted to glucose to enter glycolysis. The first step is phosphorylation to produce galactose 1-phosphate. Then, a UDP nucleotide group is exchanged between galactose 1-phosphate and UDP-glucose. The result of this reaction is the production of glucose 1-phosphate and UDP-galactose. UDP-galactose is enzymatically converted to UDP-glucose, which is then converted to glucose 1-phosphate in the next round of this loop. Glucose 1-phosphate is isomerized to produce glucose 6-phosphate, part of the glycolytic pathway. The complex polysaccharides starch and glycogen differ in their source and in their structure (they have different bonds between each individual sugar unit) but they are both composed entirely of glucose subunits polymerized together. Starch is found in plants and is digested to release individual glucose molecules in the digestive tract that are absorbed and transported to the tissues. Glycogen is the main storage carbohydrate in animals, and is mobilized by liver and muscle to release glucose when hormones like adrenalin indicate that a burst of energy is required. When glucose is mobilized from glycogen, it is released as glucose 1-phosphate. In muscle, there is no enzyme present that converts glucose 1-phosphate to glucose, so the only fate of this glucose 1-phosphate is to enter glycolysis after being converted glucose 6-phosphate. Deficiencies in the enzymes that direct sugars into glycolysis have distinct clinical effects in some cases. Lactose intolerance is very common in many parts of the world, and is caused in adults by a reduction in the enzyme that breaks lactose down into galactose and glucose in the intestine. Some individuals suffer from the genetic condition galactosemia, in which they lack the enzymes to convert galactose to glucose. The accumulation of galactose leads to mental retardation, liver damage and cataracts unless dietary intake of galactose is controlled.

Contributor: Glenn Croston, PhD

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