R. C. Gupta Professor and Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India Carbohydrate Metabolism An Overview

Carbohydrates constitute the largest component of an average diet The most important function of carbohydrates is to provide energy Some tissues, e.g. brain and erythrocytes, get energy almost exclusively from glucose

If the conditions become anaerobic, only glucose can be used as a fuel During prolonged exercise, even muscles depend upon glucose as a source of energy Besides providing energy, carbohydrates perform some other functions also

Some carbohydrates act as structural constituents of tissues Ribose and deoxyribose are used to synthesize nucleotides and nucleic acids Some carbohydrates form the prosthetic group of hormones, immunoglobulins, blood group substances etc

Digestion Carbohydrates are consumed in diet mostly as polysaccharides Dietary polysaccharides include starch, glycogen, cellulose etc Small amount of disaccharides and mono- saccharides are also present in food

Disaccharides and monosaccharides present in diet include sucrose, lactose, fructose, glucose etc The intestinal mucosa can absorb only monosaccharides Larger carbohydrates are hydrolysed into monosaccharides during digestion

Enzymes that can digest carbohydrates are present in: SalivaPancreatic juiceIntestinal secretion

Saliva contains an amylase which can hydrolyse starch and glycogen But food stays in the mouth for a very short period Contribution of salivary amylase in the digestion of carbohydrates is very small

Digestion of carbohydrates really begins in the small intestine The next digestive secretion that can digest carbohydrates is pancreatic juice Pancreatic juice also contains an amylase

Pancreatic amylase (  -amylase): Acts at an alkaline pH Hydrolyses the internal  -1,4-glyco- sidic bonds of starch and glycogen Converts starch and glycogen into maltose, isomaltose and maltotriose

Amylase does not act on: Terminal  -1,4-glycosidic bonds The  -1,6-glycosidic bonds present at branch points

Intestinal secretion contains various disaccharidases: Maltase IsomaltaseSucraseLactase

Maltase hydrolyses maltose and malto- triose into glucose Isomaltase (  -1,6-glucosidase) hydrolyses isomaltose into glucose Sucrase (invertase) hydrolyses sucrose into glucose and fructose Lactase hydrolyses lactose into glucose and galactose

Hereditary lactase deficiency in children can cause lactose intolerance Acquired lactase deficiency can occur in adults Lactase deficiency can cause diarrhoea and flatulence on ingestion of milk

Thus, the major products of digestion of carbohydrates are glucose, fructose and galactose Small amounts of mannose, ribose, xylose etc may also be present in food

Cellulose cannot be digested in human beings but its presence in food is important Cellulose stimulates peristalsis and helps in bowel movement

Absorption Monosaccharides are absorbed mainly in the small intestine Purpose of absorption is to transfer monosaccharides from the intestine into the circulation

Monosaccharides are absorbed from the lumen of intestine into the mucosal cells From mucosal cells, they are released into portal circulation Portal blood delivers the monosaccharides to the liver

All the pathways of carbohydrate metabolism are present in liver Circulating glucose is taken up and utilized by all the tissues Liver also releases glucose into systemic circulation

There are two mechanisms for absorption of monosaccharides from the intestine: Active transportFacilitated diffusion

For active transport, the monosaccharides should have: A pyranose ring structure with a methyl or a substituted methyl group on carbon 5 An –OH group on carbon 2 having the same configuration as in D-glucopyranose

Other monosaccharides are absorbed by facilitated diffusion Monosaccharides meeting the criteria for active transport are glucose and galactose

Active transport Occurs against concentration gradient Energy is spent to move the compound from lower to higher concentration A carrier (a protein molecule) is required for active transport The process is saturable

Glucose is absorbed actively from the intestinal lumen into the mucosal cells by Sodium Glucose Transporter (SGLT 1) SGLT 1, present in the cell membrane, has two binding sites – one for sodium and the other for glucose Sodium and glucose, present in the lumen, bind to SGLT 1

SodiumGlucose

Concentration of sodium in the lumen of the intestine is much higher than in the mucosal cells At the same time, glucose is transported into the mucosal cells against its concentration gradient Sodium is transported into the mucosal cells down its concentration gradient

The intracellular sodium concentration has to be kept low For this, sodium is actively pumped out of mucosal cells into the capillaries A rise in sodium concentration in intra- cellular fluid is physiologically intolerable

For every three sodium ions pumped out, two potassium ions move into the cell Pumping of sodium occurs against its concentration gradient

Ejection of sodium against its concen- tration gradient requires energy Energy is provided by hydrolysis of ATP into ADP and Pi The hydrolysis is catalysed by membrane- bound Na +, K + -exchanging ATPase

Thus, transport of glucose into mucosal cells tends to disturb sodium homeostasis Energy is spent really to maintain sodium homeostasis The system that exchanges sodium and potassium ions is also known as sodium pump or sodium-potassium pump

Galactose is also absorbed similarly by SGLT 1 Active transport is disrupted by ouabain which inhibits the sodium pump Active transport is also disrupted by phlorhizin which displaces sodium from the carrier

Facilitated diffusion Occurs down the concentration gradient Carrier (a protein) is requiredNo energy is required

After a meal, fructose concentration in the lumen of intestine increases The concentration becomes higher than in mucosal cells Fructose is absorbed into mucosal cells by facilitated diffusion The carrier involved in fructose transport is GLUT 5

GLUT5 is present on luminal side of the mucosal cells Another transporter, GLUT 2, is present on the contra-luminal side GLUT2 transports glucose, galactose and fructose by facilitated diffusion

Concentration of glucose, galactose and fructose in mucosal cells increases after their absorption They are transported into capillaries by GLUT2 down their concentration gradient

Monosaccharides released from intestinal mucosa into capillaries enter portal veins Their first destination is liver All pathways of carbohydrate metabolism are present in liver Glucose and galactose/fructose can be converted into each other in liver

Excess glucose can be stored in liver as glycogen Non-carbohydrates can be converted into glucose in liver Liver also releases glucose into systemic circulation

All the tissues take up glucose from circulation For uptake of glucose, tissues require Glucose Transporters (GLUTs) Different tissues possess different glucose transporters having different features

Trans- porter LocationSpecificityEnergy depen- dence Insulin depen- dence SGLT 1Luminal side of enterocytes and renal tubular cells Glucose, galactose YesNo GLUT 1ErythrocytesGlucoseNo GLUT 2Contraluminal side of enterocytes, liver and renal tubular cells Glucose, galactose, fructose No GLUT 3BrainGlucoseNo GLUT 4Adipocytes, muscles and myocardium GlucoseNoYes GLUT 5Luminal side of enterocytes and liver FructoseNo Salient features of glucose transporters

SGLT 1 is the only energy-dependent transporter GLUT 4 is the only insulin-dependent transporter Insulin translocates GLUT 4 from cytosol to the cell membrane

Metabolic pathways for carbohydrates EMB-RCG The pathways for metabolism of carbohydrates include: Glycolysis Hexose monophosphate shunt Glycogenesis Glycogenolysis Gluconeogenesis Uronic acid pathway

Glycolysis is the main pathway for oxidation of glucose The end product of glycolysis is pyruvate or lactate Two molecules of pyruvate/lactate are formed from one glucose molecule The purpose of this pathway is to capture the energy present in glucose

Hexose monophosphate shunt is another pathway for oxidation of glucose Pentoses are formed as intermediates in this pathway This pathway also provides NADPH

Glycogenesis is the pathway for storage of glucose as glycogen Major sites for storage of carbohydrates are liver and muscles Glycogenolysis is the pathway by which stored glycogen is broken down

Gluconeogenesis is a pathway by which glucose is formed from non-carbohydrates This pathway becomes active when dietary carbohydrates are not available It also becomes active when glucose cannot be utilized e.g. in diabetes mellitus

Uronic acid pathway is a pathway for synthesis of glucuronic acid from glucose Glucuronic acid is required for some conjugation and detoxification reactions In some species, ascorbic acid is synthesized by this pathway

There are also pathways for metabolism of: Galactose Fructose Amino sugars etc