Carbohydrate Digestion —

The objectives of this section are to indicate

Dietary carbohydrate may be ingested as monosaccharides, disaccharides and complex polymers.

• Digestion requires the hydrolysis of complex polymers to monosaccharides and disaccharides by salivary and pancreatic enzymes.

• Monosaccharides and disaccharides are absorbed through specific intestinal mucosal transport systems.

• Carbohydrates may be metabolized within the enterocytes.

• Specific transport systems, different from those of the luminal side of the intestine, transport disaccharides and monosaccharides across the cell basal membrane to the body.

Introduction

Dietary carbohydrate accounts for approximately half of the energy intake in the average western diet. Some 60% of the carbohydrate is in the form of starch and glycogen; sucrose and lactose may contribute 30% and 10%, respectively. There may also be glucose and fructose in certain foods. Raffinose and stacchyose are present in small amounts in beans and are not absorbed in the upper intestine but are fermented in the colon. The polysaccharides are digested by salivary and pancreatic amylase in the lumen of the intestine. Starch digestion is intraluminal. There is further hydrolysis of the glucosyl oligosaccharides by the digestive, absorptive brush border enterocytes.

Intestinal digestive and absorptive function declines with advancing age, so there may be reduced absorption of carbohydrates in about one-third of healthy individuals over the age of 65 years.

1. In many diets, the carbohydrate is 60% in the form of starch and glycogen, 30% as sucrose and 10% as lactose. Raffinose and stacchyose are present in small amounts in beans and are not absorbed in the upper intestine but are fermented in the colon.

2. The osmolarity of a sugar solution influences gastric emptying time and intestinal transit time. Other determinants of gastric emptying include duodenal pH, fat and caloric intake, viscosity, the solid content of the meal and whether the carbohydrate is a mono- or a disaccharide.

3. Oligosaccharides in general are efficiently absorbed and metabolised after hydrolysis into the basic monosaccharides. The hydrolysis of lactose is relatively slow.

4. Fructose is not absorbed readily as the monosaccharide, but as a constituent of sucrose is very easily absorbed.

5. Monosaccharides cross the intestinal epithelium by one of three processes: simple diffusion, facilitated diffusion and active transport. The Na+active transfer of hexoses has a specific membrane carrier system, a co-transporter with two binding sites: one for the hexose and the other for the Na+ ion.

6. Three major transfer systems are known: (i) a brush border Na+/glucose co-transporter (SGLT1); (ii) a brush border fructose transporter (GLUT5); and (iii) a basolateral facilitated sugar transporter (GLUT2)

7. The brush border disaccharidases hydrolyse maltose, sucrose and lactose to the monosaccharides glucose, galactose and fructose. There is a kinetic advantage of hexoses being liberated from disaccharides, namely enhanced absorption rates from the lumen over those for free hexoses.

8. The brush border enzymes function on specific glycoside linkages. The disaccharidases are all large protein heterodimers or single subunits, anchored with transmembrane domains, most of the protein protruding into the intestinal lumen.

9. Lactase is an unusual enteric enzyme which is present at birth and persists through life for Caucasian races but not in most other races.

10. Starch consists of the linear a -1–4-linked α-d-glucose (amylose) and the highly branched amylopectin with a -1–4 and a -1–6 glycosidic links. Salivary and pancreatic a -amylases act on the endo- a -1–4 links within starch, but do not digest the exo- a -glucose-glucose linkages.

11. Starch may be classified nutritionally on the basis of its enzymatic hydrolysis: (i) rapidly digestible starch; (ii) slowly digestible starch; and (iii) resistant starch (which is not hydrolysed by pancreatic enzymes). Starch which is not digested in the intestine passes to the colon for fermentation by colonic bacteria.

12. Tolerance tests of carbohydrate loads allow changes in blood glucose to be estimated for carbohydrates of different food sources and compared against a standard carbohydrate (glucose or white bread). This allows a glycaemic index to be calculated.

Carbohydrate Metabolism —

Despite their central importance for metabolic processes, carbohydrates are not in the strict sense essential nutrients. Nevertheless, glucose is an important constituent in the provision of energy to the body and in that respect is essential. If the carbohydrate content of the diet is reduced or low then more expensive and less immediately utilisable energy sources such as fat and protein have to be used. This is expensive nutritionally and metabolically.

Dietary carbohydrates, whether eaten as starches, glycogen or glucose are metabolised as their constituent monosaccharides. The presence of the monosaccharides, glucose, galactose and fructose in tissues is essential for normal nutritional development.

1. Glucose is an important energy source to the body. Blood glucose is derived from food, liver glycogen and intermediary metabolites.

2. Glucose may be taken up by tissues, particularly skeletal muscles. Insulin facilitates the active transport of glucose into the muscle and fat cells. Postprandially there is massive glycogen synthesis. During fasting glycogen may be hydrolysed to glucose 1-phosphate and thence to pyruvate in the liver.

3. Galactose is absorbed through the same active transport system in the small intestine as glucose. A small amount enters the peripheral circulation as galactose, is converted in the small intestine epithelium cells to galactose 1-phosphate and then to glucose 1-phosphate. Galactose required for structure in body cells and connective tissue, e.g. galactosamine is produced from glucose.

4. Dietary fructose is taken up by the liver and enters directly into glycolytic pathway. Within the liver fructose is phosphorylated to fructose 1-phosphate, which is split into glyceraldehyde and dihydroxyacetone phosphate; the latter is an intermediate in both the glycolytic and gluconeogenic pathways. Glyceraldehyde is converted to glyceraldehyde 3-phosphate then to glycogen, a source of glucose. Glyceraldehyde can also be converted to glycerol 3-phosphate and esterified to fatty acids in triglycerides. These reactions are dictated by nutrition and hormonal state. Fructose enters cells regardless of the insulin concentration.

5. Most of the enzymes involved in carbohydrate metabolism require vitamin B metabolites as essential cofactors in the glycolytic pathway, pentose phosphate shunt and tricarboxylic acid cycle.

6. Sugars may react with free amino groups on proteins to produce a chemically reversible glycosylated product (a Schiff base) and by internal rearrangement to produce a more stable Amadori-type glycosylation product, an advanced glycosylation end-product.

7. A carbohydrate meal ( eg starch or glucose but not fructose ) increases blood glucose.. A number of factors affect the measurement of the glycaemic response to meals.

8. Triglyceride long-chain fatty acids come from the diet or are synthesised from products of the glycolytic pathway and the pentose phosphate shunt. Blood borne glucose requires insulin to enter adipocytes. Without insulin stimulation, glucose does not enter the cells and glycolysis decreases. Prolonged exposure to high carbohydrate diets raises the fasting serum triglyceride concentration.

9. The ratio of carbon dioxide to oxygen in the breath (the respiratory quotient, RQ), indicates the substrate being metabolised and which metabolic route is being followed. The RQ after ingestion of fructose is greater than that after glucose.

10. ATP yield for each glucose molecule metabolised aerobically is 20-fold greater than anaerobically. The free energy is conserved as ATP and there is continuous re-oxidation of reduced coenzymes, e.g. NADH and FADH2which link into the respiratory chain to produce ATP The oxidised coenzymes are involved in the oxidation of pyruvate intermediates.

11. During aerobic conditions the glycolytic pathway is the initial phase of glucose catabolism leading to the tricarboxylic acid cycle and the oxidative phosphorylation of ADP to ATP, yielding 36–38 moles of ATP for each mole of glucose.

12. Glycolysis is the pathway in which glucose is metabolised before splitting into two interconvertible, 3-carbon molecules in the cell cytoplasm.

13. The catabolic steps are glycolysis with fructose 6-phosphate (F6P) as the starting point or the pentose phosphate pathway which uses glucose 6-phosphate (G6P). Alternatively, G6P and F6P can be converted into storage polysaccharides with G6P acting as the starting point. Fructose 1,6-diphosphate is reversibly split into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

14. Glyceraldehyde 3-phosphate is converted to 1,3-diphosphoglycerate with a high-energy phosphoanhydride bond on carbon-1. Two ATP are regenerated with the coincidental production of pyruvate which is transferred into the mitochondria. Pyruvic acid has to be converted to acetyl CoA in the mitochondria, where the tricarboxylic acid (TCA) cycle takes place.

15. Pyruvate plays a major role as an intermediary metabolite and is central to the interconversion of glucose, fatty acids and amino acids.

16. In the TCA cycle the most important supply of acetyl-CoA is from pyruvate, fatty acids and amino acids.

17. The TCA cycle is regulated to provide for cell needs. The function of the cycle is to provide NADH and FADH2 for the electron transport chain and to provide substrates for biosynthesis.

18. Acetyl-CoA entering the TCA cycle yields I ATP molecule and storage of free energy as NADH and FADH2. Oxidation of 1 mole of acetyl-CoA leads to the overall production of 12 moles of ATP In addition, pyruvate metabolism provides 15 moles of ATP per mole of pyruvate or 30 moles per mole of glucose. The metabolites in the TCA cycle are major starting materials for a number of biosynthetic pathways.

19. The pentose phosphate pathway is a an alternative metabolic pathway. The initial reaction of glucose 6-phosphate dehydrogenation generates NADPH for fatty acid and cholesterol synthesis. The NADPH production throughout the pathway is important for some biosynthetic reactions, especially lipids.

20. In the presence of abundant glucose the emphasis is on anabolic processes and storage. The liver converts some glucose to stored glycogen and some to fatty acids to be used as a fuel. Peripherally glucose is metabolised to generate ATP and excess is stored as glycogen and adipose tissue.

21. Insulin stimulates the uptake of glucose by various tissues and the synthesis of glycogen in the liver.

22. Glycogen is an a -1–4 polysaccharide with a -1–6 branch points. Glycogen synthase is inactive when phosphorylated, and is activated by insulin and high concentrations of G6P

23. Glucose stores in the form of glycogen are mobilised when needed. Glucose synthesis from non-glucose sources, lactate, pyruvate, fatty acids or amino acids (gluconeogenesis) is stimulated in liver and kidney.

24. Phosphorylase releases glucose from glycogen in the form of G6P The enzyme phosphorylase a is active when phosphorylated. The inactive form phosphorylase b is produced by phosphorylase a phosphatase. The phosphorylase kinase is kept in an active and inactive form by protein kinase, the process being controlled hormonally.

25. Glucose has a central role in the production and harnessing of energy and in the synthesis of other sugars. While an individual is fasting the brain uses 80% of the glucose consumed. The liver only contains sufficient glucose (as glycogen stores) to meet the needs of the brain for 12 hours.

26. Glycolysis and gluconeogenesis are directly opposed reaction sequences. Most of the enzymes that function in glycolysis are reversed in gluconeogenesis. Fatty acids are not capable of undergoing gluconeogenesis.

27. The intermediates in the gluconeogenic and glycolysis pathways are the same and are coupled to the ATP-ADP system. Some steps in metabolic pathways are irreversible, hence alternative pathways are necessary.

28. The energy difference between glycolysis and gluconeogenesis is 4 ATP molecules per metabolised hexose. This means that regulation of the glycolysis and gluconeogenesis systems is of prime importance to cellular metabolism. There is a direct effect of concentrations of metabolites within the TCA cycle on phosphofructokinase activity.

29. During starvation or high protein or fat diets, the amount and activity of phosphoenolpyruvate carboxykinase increases and decreases when there is a restoration of carbohydrate to the diet.

30. Ketone bodies are acetoacetate (AcAc), b -hydroxybutyrate (BHB) and acetone. AcAc and BHB are interconvertible within mitochondria using the NAD+/NADH2 couple as a cofactor.

31. Ketone bodies are synthesised almost entirely in the liver, resulting in 3-hydroxybutyrate. There is diffusion from the liver cell into the plasma. The brain, but not the liver, is able to metabolize ketone bodies.

32. During starvation ketone body synthesis begins and plasma concentrations of AcAc and BHB become detectable. During prolonged starvation and diabetes mellitus high concentrations of ketones appear in the blood, the condition of ketosis.

32. The genetic control of transport of sugars and the subsequent metabolism is mediated through the transported sugar or by a metabolite and hormones eg insulin.