162 Metabolism of Nutrients

Connecting Other Sugars to Glucose Metabolism

Sugars, such as galactose, fructose, and glycogen, are catabolized into new products in order to enter the glycolytic pathway.

You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways. 

Metabolic pathways should be thought of as porous; that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Like sugars and amino acids, the catabolic pathways of lipids are also connected to the glucose catabolism pathways.

Glycogen Pathway: Glycogen from the liver and muscles, hydrolyzed into glucose-1-phosphate, together with fats and proteins, can feed into the catabolic pathways for carbohydrates.

Glycogen, a polymer of glucose, is an energy-storage molecule in animals. When there is adequate ATP present, excess glucose is shunted into glycogen for storage. Glycogen is made and stored in both the liver and muscles. The glycogen is hydrolyzed into the glucose monomer, glucose-1-phosphate (G-1-P), if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into G-1-P and converted into glucose-6-phosphate (G-6-P) in both muscle and liver cells; this product enters the glycolytic pathway.

Glycogen Structure: Schematic two-dimensional cross-sectional view of glycogen: A core protein of glycogenin is surrounded by branches of glucose units. The entire globular granule may contain around 30,000 glucose units.

Galactose is the sugar in milk. Infants have an enzyme in the small intestine that metabolizes lactose to galactose and glucose. In areas where milk products are regularly consumed, adults have also evolved this enzyme. Galactose is converted in the liver to G-6-P and can thus enter the glycolytic pathway. 

Fructose is one of the three dietary monosaccharides (along with glucose and galactose) which are absorbed directly into the bloodstream during digestion. Fructose is absorbed from the small intestine and then passes to the liver to be metabolized, primarily to glycogen. The catabolism of both fructose and galactose produces the same number of ATP molecules as glucose.

Fructose Metabolism: Although the metabolism of fructose and glucose share many of the same intermediate structures, they have very different metabolic fates in human metabolism.

Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage. The catabolism of sucrose breaks it down to monomers of glucose and fructose. The glucose can directly enter the glycolytic pathway while fructose must first be converted to glycogen, which can be broken down to G-1-P and enter the glycolytic pathway as described above.

Connecting Proteins to Glucose Metabolism

Excess amino acids are converted into molecules that can enter the pathways of glucose catabolism.

Metabolic pathways should be thought of as porous; that is, substances enter from other pathways and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Proteins are a good example of this phenomenon. They can be broken down into their constituent amino acids and used at various steps of the pathway of glucose catabolism.

Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are recycled into the synthesis of new proteins or are used as precursors in the synthesis of other important biological molecules, such as hormones, nucleotides, or neurotransmitters. However, if there are excess amino acids, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism.

Connection of Amino Acids to Glucose Metabolism Pathways: The carbon skeletons of certain amino acids (indicated in boxes) are derived from proteins and can feed into pyruvate, acetyl CoA, and the citric acid cycle.

Each amino acid must have its amino group removed (deamination) prior to the carbon chain’s entry into these pathways. When the amino group is removed from an amino acid, it is converted into ammonia through the urea cycle. The remaining atoms of the amino acid result in a keto acid: a carbon chain with one ketone and one carboxylic acid group. In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste product in mammals produced from the nitrogen originating in amino acids; it leaves the body in urine. The keto acid can then enter the citric acid cycle.

When deaminated, amino acids can enter the pathways of glucose metabolism as pyruvate, acetyl CoA, or several components of the citric acid cycle. For example, deaminated asparagine and aspartate are converted into oxaloacetate and enter glucose catabolism in the citric acid cycle. Deaminated amino acids can also be converted into another intermediate molecule before entering the pathways. Several amino acids can enter glucose catabolism at multiple locations.