Lec 5 level 3-nu(carbohydrate metabolism i)


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Lec 5 level 3-nu(carbohydrate metabolism i)

  1. 1. Nursing - 5Introduction to carbohydrates and Glycolysis
  2. 2. Function of carbohydrates• Carbohydrates are the most abundant organic molecules in nature• providing a significant fraction of the energy in the diet of most organisms.• Acting as a storage form of energy in the body.• Serving as cell membrane components that mediate some forms of intercellular communication.• Serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. 2
  3. 3. CLASSIFICATIONCarbohydrates are classified into three main groups:• 1) Monosaccharides (simple sugars) : They consist of asingle polyhydroxyaldehyde(glucose) or ketone units(fructose). They can not be hydrolysed into simplerunits. The sugar unit is sometimes referred to asglycan.• 2) Oligosaccharides (oligo= few) : contain from two toten monosaccharide units joined in glycosidic bonds.e.g. disaccharides (2 units) e.g. maltose and sucrose,trisaccharides(3 units).....etc.• 3) Polysaccharides (poly = many): Also known as glycans.They are composed of more than ten monosaccharideunits e.g. starch, glycogen, cellulose.....etc. 3
  4. 4. Monosaccharides• They have the common formula (CH2O)n, where n = 3 or some larger number 4
  5. 5. • Isomers, epimers and enantiomers:• Compounds that have the same chemical formula but have different structures are called isomers. Eg. fructose, glucose, mannose, and galactose are all isomers.• two monosaccharides differ in configuration around only one specific carbon atom, they are defined as epimers of each other. Eg. glucose and galactose are C-4 epimers.• A special type of isomerism is found in the pairs of structures that are mirror images of each other.• These mirror images are called enantiomers, and the two members of the pair are designated as a D- and an L-sugar.• The vast majority of the sugars in humans are D-sugars. 5
  6. 6. 6
  7. 7. Galactose7
  8. 8. CLASSIFICATION OF MONOSACCHARIDES• Can be carried out by one of two methods: 1) According to the number of carbon atoms : Trioses, Tetroses, Pentoses, Hexoses, Heptoses, Octoses.8
  9. 9. • 2) According to the characteristic carbonyl group:Aldehyde group or ketone group a) Aldo sugars: Aldoses :Monosaccharides containing aldehyde group e.g. glucose, ribose. b) Keto sugars: Ketoses :Monosaccharides containing ketone group e.g. fructose, ribulose. 9
  10. 10. Complex carbohydrates• Carbohydrates can be attached by glycosidic bonds to non-carbohydrate structures, including:• purines and pyrimidines (found in nucleic acids),• aromatic rings (such as those found in steroids and bilirubin),• proteins (found in glycoproteins and glycos- aminoglycans)• lipids (found in glycolipids). 10
  11. 11. A. Digestion of carbohydrates begins in the mouth• The major dietary polysaccharides are of animal (glycogen) and plant origin (starch, composed of amylose and amylopectin).• During mastication, salivary α-amylase acts briefly on dietary starch in a random manner, breaking some α(1- 4) bonds.• Because branched amylopectin and glycogen also contain α(1- 6) bonds, the digest resulting from the action of α-amylase contains a mixture of smaller, branched oligosaccharide molecules. 11
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  13. 13. • Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates the salivary α-amylase.• Note: There are both α(1- 4) and β(1- 4)- endoglucosidases in nature, but humans do not produce and secrete the latter in digestive juices. Therefore,• they are unable to digest cellulose—a carbohydrate of plant origin containing β(1- 4) glycosidic bonds between glucose residues.13
  14. 14. B. Further digestion of carbohydrates by pancreatic enzymes occurs in the small intestine• 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. 14
  15. 15. • C- Digestion by intestinal enzymes:• The final digestive processes occur at the mucosal lining of upper jejunum by enzymes synthesized by the intestinal mucosal cells.• Brush borders intestinal enzymes are:• 1- Oligo 1,6 glucosidase releases glucose residues from branched oligosaccharides.• 2- disaccharidasess• - Sucrase converts sucrose to glucose and fructose.• - Lactase converts lactose to glucose and galactose.• - Maltase converts maltose to two glucose molecules 15
  16. 16. D. Absorption of monosaccharides by intestinal mucosal cells• The duodenum and upper jejunum absorb the bulk of the dietary sugars.• Insulin is not required for the uptake of glucose by intestinal cells.• However, different sugars have different mechanisms of absorption.1. galactose and glucose are transported into themucosal cells by an active, energy-requiring processthat involves a specific transport protein and requiresa concurrent uptake of sodium ions. 16
  17. 17. 2. Fructose uptake requires a sodium-independent monosaccharide transporter(GLUT-5) for its absorption.3. All three monosaccharides aretransported from the intestinal mucosal cellinto the portal circulation by yet anothertransporter, GLUT-2.17
  18. 18. Glucose metabolismImportance of Glucose:1. Glucose is the preferred source of energy for most of the body tissues. Brain cells derive energy mainly from glucose.2. When glucose metabolism is deranged, life- threatenung conditions may occur. A minimum amount of glucose is always required for normal functioning.3. Normal fasting plasma glucose level is 70 to 110 mg/dl. After a heavy carbohydrate meal, in a normal person, this level is below 150 mg/dl. 18
  19. 19. • Glucose is used in:• Oxidation:• The pathways for oxidation of glucose are classified into two main groups:• A. The major pathways which are mainly for energy production:• 1. Glycolysis.• 2. Citric acid cycle (CAC).• B. The minor pathways for oxidation which are not for energy production:• 1. Hexose monophosphate shunt (HMS).• 2. Uronic acid pathway. 19
  20. 20. • II. Conversion to biologically active substances as:• 1. Galactose: which is essential for formation of lactose, glycolipids, mucopolysaccharides, ...etc.• 2. Fructose: needed for nutrition of sperms.• 3. Amino sugars.• 4. Non-essential amino acids.• 5. Fatty acids.• 6. Ribose-5-P.• 7. Glucuronic acid. 20
  21. 21. • III. Storage of glucose:• 1. As glycogen in the liver and muscles mainly.• 2. As triglycerides (TG), mainly in adipose tissues.• IV. Excretion of glucose in urine:• When blood glucose level exceeds a certain limit (renal sugar threshold), it will pass to urine. This will occur when blood glucose level is above 180 mg/dl and this is known as glucosuria.21
  22. 22. Glycolysis (Embden Meyerhof Pathway)Definition:• It is degradation of glucose to generate ATP and to provide intermediates for other synthetic and metabolic pathways. Aerobically it ends with pyruvate while anaerobically lactate is the end product. Site of glycolysis:• It occurs in the cell cytosol of all tissues. 22
  23. 23. Glycolysis (Embden-Meyerhof Pathway)Importance of the pathway• In this pathway glucose is converted to pyruvate (aerobic condition) or lactate (anaeroboic condition), along with production of a small quantity of energy.• Glycolysis is the only source of energy in erythrocytes. 23
  24. 24. • In strenuous exercise, when muscle tissue lacks enough oxygen, anaerobic glycolysis forms the major source of energy for muscles.• The glycolytic pathway may be considered as the preliminary step before complete oxidation.• The glycolytic pathway also provides carbon skeleton for synthesis of certain nonessential amino acids as well as glycerol part of fat.• Most of the reactions of the glycolytic pathway are reversible, which are also used 24 for gluconeogenesis.
  25. 25. • Steps of glycolysis:• Conversion of glucose to G-6-P, is irreversible (non-equilibrium reaction). It is catalyzed by glucokinase (in liver and pancreas) or by hexokinase (in all other tissues).• Aldolase A: (F1,6 diphosphate aldolase) Occurs in most tissues. Two molecules of ATP are liberated in each step since every molecule of glucose gives rise to two trioses.25
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  28. 28. Energy production1. Under aerobic conditions: Glucose ------→ 2 Pyruvate + 8 ATP. For tissues that have mitochondria, glycolysis is considered a preparatory step for complete oxidation via citric acid cycle since pyruvate is transported into the mitochondria to provide oxaloacetate or active acetate where it is oxidized by citric acid cycle for more energy. 28
  29. 29. • The hydrogens of NADH produced by glycolysis are transported to the mitochondria mainly to be oxidized by electron transport chain (ETC).• 2. Under anaerobic conditions: Glucose ------→ 2 lactate + 2 ATP Pyruvate is reduced to lactate in a reversible reaction catalyzed by lactate dehydrogenase (LDH). 29
  30. 30. • This occurs in muscles during severe exercise (hypoxic conditions) and in tissues that lack mitochondria as RBCs and lens.30
  31. 31. Cori’s cycle or lactic acid cycle• In an actively contracting muscle, only about 8% of the pyruvate is utilized by the citric acid cycle, and the remaining molecules are therefore reduced to lactate.• The lactic acid thus, generated should not be allowed to accumulate in the muscle tissues.• The muscle cramps, often associated with strenuous muscular exercise, are through to be due to lactate accumulation.31
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  33. 33. Regulation of glycolysis Hormonal regulation of glycolysis:• a) Glucagon : is secreted in hypoglycemia or in carbohydrate deficiency. It affects liver cells mainly as follows: It acts as inhibitors for glycolytic key enzymes (glucokinase,PFK-1, pyruvate kinase).• b) Insulin: It is secreted in hyperglycemia and after carbohydrates feeding, it causes: Stimulation of glycolytic key enzymes. 33
  34. 34. Inhibitors of glycolysis:1- 2- deoxyglucose inhibits hexokinase.2- Mercury and iodoacetate inhibit glyceraldehyde-3-P dehydrogenase.3- Fluoride inhibits enolase by removal of Mg2+ as Mg fluoride.34