• Define intermediary metabolism • Describe digestion process of carbohydrates • Identify absorption mechanism of monosacharides • Identify carbohydrate metabolism disorders
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09/16/2023 Figure: Three stagesBy Amanuel of catabolism Tobe 3 3 Catabolic vs anabolic reactions
Catabolic reactions (blue arrows) and anabolic ones (green)
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Digestion of carbohydrates
• In the diet, carbohydrates are present as complex
polysaccharides (starch, glycogen), and to a minor extent, as disaccharides (sucrose and lactose). They are hydrolyzed to monosaccharide units in the gastrointestinal tract. Cooking makes the digestion process easier. • The process of digestion starts in mouth by the salivary alpha-amylase.
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Cont.
• However, the time available for digestion in the mouth is
limited, because the gastric hydrochloric acid will inhibit the action of salivary amylase. • During mastication, salivary α-amylase acts briefly on dietary starch and glycogen, hydrolyzing random α(1→4) bonds. • There are both α(1→4)- and β(1→4)-endoglucosidases in nature, but humans do not produce the latter. Therefore, we are unable to digest cellulose, a carbohydrate of plant origin containing β(1→4) glycosidic bonds between glucose residues.
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• Because branched amylopectin and glycogen also contain
α(1→6) bonds, which α-amylase cannot hydrolyze, the digest resulting from its action contains a mixture of short, branched and unbranched oligosaccharides known as dextrins. • When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic α-amylase continues the process of starch digestion.
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Cont.
• In the pancreatic juice another alpha-amylase is available
which will hydrolyse the alpha-1,4 glycosidic linkages randomly, so as to produce smaller subunits like maltose, isomaltose, dextrins and branched or unbranched oligosaccharides. • The cells of brush border of intestine contain the enzymes, sucrase, maltase, isomaltose and lactase. They hydrolyse the corresponding disaccharides into component monosaccharides which are then absorbed.
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Cellulose
Fig. Overview of carbohydrate digestion
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Figure: Overview of carbohydrateBydigestion 09/16/2023 Amanuel Tobe 10 Cont.
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Cont.
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The dietary carbohydrates are present in three forms:
A. Ready-to-absorb carbohydrates: The carbohydrate molecules,
which do not require digestion and are absorbed as such, e.g., monosaccharides: glucose, mannose, galactose, fructose and pentoses. B. Digestible carbohydrates: They are completely digested into their respective monosaccharides. These include starch (constitutes more than 50%), glycogen, maltose, sucrose, and lactose (oligosaccharides and polysaccharides). C. Non-digestible carbohydrates: There are carbohydrate molecules (dietary fibers) that cannot be digested in human gastrointestinal tract primarily due to the absence of specific digestive enzymes.
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Cont.
• Glycosidases are usually specific for the structure and
configuration of the glycosyl residue to be removed as well as for the type of bond to be broken. The final products of carbohydrate digestion are the monosaccharides, glucose, galactose, and fructose that are absorbed by cells of the small intestine.
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Absorption of carbohydrates
• Only monosaccharides are absorbed by the intestine.
Absorption rate is maximum for galactose; moderate for glucose; and minimum for fructose.
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SGluT-1. Sodium and glucose co-
transport system at luminal side Glucose absorption (GluT2)
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Mutation in SGLT1 leads to the potentially fatal neonatal glucose-galactose malabsorption, correctable by dietary fructose as a main sugar. 09/16/2023 By Amanuel Tobe 18 Glucose transporters in specific cells
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Absorption of other monosaccharides
• Glucose and galactose are absorbed by the same transporter,
SGluT1. It is an energy dependent process, against a concentration gradient, and therefore absorption is almost complete from the intestine. • Other monosaccharides are absorbed by carrier mediated facilitated transport. Therefore, absorption is not complete, and the remaining molecules in the intestine will be fermented by bacteria.
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• The overall process of carbohydrate digestion and absorption
is so efficient in healthy individuals that ordinarily all digestible dietary carbohydrate is absorbed by the time the ingested material reaches the lower jejunum. However, because only monosaccharides are absorbed, any deficiency (genetic or acquired) in a specific disaccharidase activity of the intestinal mucosa causes the passage of undigested carbohydrate into the large intestine.
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• As a consequence of the presence of this osmotically active
material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea. This is reinforced by the bacterial fermentation of the remaining carbohydrate to two- and three-carbon compounds (which are also osmotically active) plus large volumes of CO2 and H2 gas, causing abdominal cramps, diarrhea, and flatulence.
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Digestive enzyme deficiencies
• Genetic deficiencies of the individual disaccharidases result in
disaccharide intolerance. Alterations in disaccharide degradation can also be caused by a variety of intestinal diseases, malnutrition, and drugs that injure the mucosa of the small intestine. For example, brush border enzymes are rapidly lost in normal individuals with severe diarrhea, causing a temporary, acquired enzyme deficiency.
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Cont.
• Lactose intolerance: More than 70% of the world’s adults are
lactose intolerant. This is particularly manifested in certain populations. For example, up to 90% of adults of African or Asian descent are lactase-deficient and, therefore, are less able to metabolize lactose than individuals of Northern European origin. The age-dependent loss of lactase activity represents a reduction in the amount of enzyme produced.
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Cont.
• Treatment for this disorder is to reduce consumption of milk
and eat yogurts and some cheeses (bacterial action and aging process decrease lactose content) as well as green vegetables, such as broccoli, to ensure adequate calcium intake; to use lactase-treated products; or to take lactase in pill form prior to eating.
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Clinical Importance of Glucose
1. Glucose is the preferred source of energy for most of
the body tissues. Brain cells derive the energy mainly from glucose. 2. When the glucose metabolism is deranged, life-threatening conditions may occur. A minimum amount of glucose is always required for normal functioning. 3. Normal fasting plasma glucose level is 70 to 100 mg/dl. After a heavy carbohydrate meal, in a normal person, this level is below 150 mg/dl.