Glucose : (Every Cell)

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Glucose : (Every Cell) المقرر الكود المستوى المحاضرات نوع المادة العلمية بيانات التواصل من 6 إلى آخر أساسيات وأيض 203 ك ح الثاني محاضرة بالفصل PDF 01003899211 الكربوهيدرات الدراسي الثاني Course of General Metabolism 1. Lipids Metabolism (finished) 2. Carbohydrates Metabolism 3. Proteins Metabolism Metabolism In living organisms Microorganisms Plans Animals Human We have learned metabolism from other organisms Biological process in living organisms Digestion Absorption Excretion Metabolism Metabolism The Greek metabole, meaning change. It is the totality of an organism's chemical processes to maintain life. Anabolism Catabolism Amphibolic Building compounds Oxidative process Links between the need energy release free energy other two pathways (~P) e.g. Protein synthesis e.g. Krebs Cycle e.g. Glycolysis Biomedical Importance of metabolism Normal Metabolism Abnormal Metabolism A knowledge of It results from: ●- Nutritional deficiency metabolism in normal ●- Enzyme deficiency animal is a prerequisite to ●- Abnormal secretion of Hormones understand abnormal ●- Genetic diseases state underlying many e.g. diabetes mellitus diseases. It includes the variations and adaptations in metabolism due to periods of Starvation, Exercise, Pregnancy, and Lactation. Carbohydrates In human body 1. Glucose : (Every cell). 2. Galactose : (Lactose of milk & Galactolipids ). 3. Fructose : (Liver & Seminal fluid). 4. Lactose : (Blood & Milk of lactating female). 5. Glycogen : (Liver & Muscles). 6. Ribose and Deoxy-ribose : (RNA & DNA). 7. Glycoproteins and mucoproteins: (Prothrombin & Mucin in saliva). 8. Mucopolysaccharides : (as heparin and hyaluronic acid in connective tissues & as agglutinogens on RBCs giving what are called blood group antigens). 9. Others: (Vitamin C, D-Glucuronic acid, L-Ascorbic acid etc). Digestion of Carbohydrates ▲- A family of glycosidases degrade carbohydrates into monohexoses via catalyzing the hydrolysis of glycosidic bonds. ▲-These enzymes are usually specific to the type of bond to be broken. ▲-Each enzyme has its optimum pH. ▲-In the mouse, the digestion of complex carbohydrates starts by the action of amylase enzyme (pH= 6.8) 1. Carbohydrate Metabolism ▲-After intake and absorption of glucose (e.g. after eating or drinking ), liver condenses extra glucose to glycogen. ▲-Then: ●1/3 of the body’s glycogen is stored in liver ● it is released as glucose to bloodstream ● If blood glucose falls ( e.g. during fasting) ● liver hydrolyzes glycogen to glucose Glycogen is bulky, so, we store only so much for short term energy supply ▲-You must know that:Fats are the long term energy supply Carbohydrate Metabolism (Continued) Metabolism The chemical needed changes that take place in a cell that produce energy and basic materials for important life processes -Millions of cells are included -Multiple organs (liver, adipose, heart, brain) are involved during such process -Thousands of enzymes are used during the metabolic -Various conditions (fed, fasted, exercise, stress) 1. Digestion & Absorption of Carbohydrates. 2. Glucose Oxidation: i. Major Pathways: (Mitochondrial or aerobic pathway, TCA cycle or Krebs cycle). ii. Minor pathways: (Pentose phosphate pathway + Uronic acid pathway) 3. Metabolism of Fructose, Galactose & Mannose. 4. Metabolism of Glycogen (Glycogenolysis + Glycogenesis). 5. Gluconeogenesis. Absorption of Carbohydrates Target: Simple Sugars (Glucose, Fructose, Galactose) Tissue Cell The product of digestion provide the tissues with Hexoses: (Fuel which are used to power the living process within the cells). Digestion of carbohydrates A- Pre-stomach : Via Salivary amylase a 1-4 endoglycosidase: G G G G G a Limit dextrins G G G G G G G G G G G amylase G G G G G G G a 1-6 link G G maltotriose G G a 1-4 link G G G G G maltose G G isomaltose B-Small Intestine: • Pancreatic enzymes a-amylase maltotriose maltose G G G G G G G G + G G a amylase amylose G G G G G G G G G G G G G G G G G amylopectin a Limit dextrins In the Small intestine (continued): - Portal for transport of virtually all nutrients - Water and electrolyte balance Enzymes associated with intestinal Surface membranes i. Sucrase ii. a dextrinase iii.Glucoamylase (maltase) iv. Lactase v. peptidases Oligosaccharide digestion (cont.) G G G G c-In The Stomach • No much carbohydrate digestion (because of the high G G pH of the stomach that inhibits salivary amylase) sucrase G • Acid and pepsin to unfold proteins a Limit dextrins • Ruminants have fore stomachs with extensive microbial populations to breakdown and an aerobically ferment G G feed G G maltase Glucoamylase (maltase) or G G G a- dextrinase G G a- dextrinase G G G G G Maltase: Specifically removes a single glucose from the nonreducing end of a linear α1-4 glucose G G G chain…breaking down maltose into glucose. (exosaccharidases) G Alpha dextinase : Cleaves 1,6-alpha glucosidic linkages Glucose transporter Carbohydrate absorption (GLUT, 14 types) isoforms GLUT1, GLUT3 and GLUT4: Are primarily Involved in Glucose transporter glucose uptake from the blood -GLUT2: liver, kidney can either transport glucose to these cells (hyperglycemia) or from them into the blood ( fasting or hypoglycemia). -GLUT5: Transporter of fructose in the small intestine and tests. (PAGE 95) apical basolateral Defects of Carbohydrates Digestion & Absorption 1. Lactase deficiency: The presence of Lactose in the intestine causes an Increase in the osmotic pressure. So, water will be drawn from the tissues (causing Dehydration) into the large intestine, a process which causes Diarrhea. The increase in the fermentation of Lactose by bacteria lead to production of CO2 gas. This cause distention and abdominal cramps. Treatment: remove milk from diet. 2. Sucrase deficiency: Rare condition show the same symptoms of lactase deficiency. it occurs early in childhood. 3. Monosacchrides malabsorption: A defect in the carrier mechanism (congenital conditions) of glucose and galactose. Treatment: No treatment. Carbohydrate malabsorption ●Lactose intolerance (hypolactasia). ● Decline lactase with age ● Lactose fermented in LI – • Gas and volatile FA • Water retention • diarrhea/bloating ● Not all populations (incidence of the enzyme deficiency): • Northern European – low incidence • Asian/African Americans – High b 1-4 linkage Glycolysis Carbohydrates serve as primary source of energy in the cell and Central to all metabolic processes. Glucose Cytosol - anaerobic Hexokinase Pentose Phosphate Glucose-6-P Glc-1- phosphate Shunt Glycolysis glycogen Pyruvate 1. Digestion & Absorption of Carbohydrates. a. Glucose Oxidation: i. Major Pathways: (Mitochondrial or aerobic pathway, TCA cycle or Krebs cycle). ii. Minor pathways: (Pentose phosphate pathway + Uronic acid pathway) b. Metabolism of Fructose, Galactose & Mannose. c. Metabolism of Glycogen (Glycogenolysis + Glycogenesis). d. Gluconeogenesis. Glycolysis (continued) * Oxidation of glucose is known as Glycolysis. * Glucose is oxidized to either Pyruvate or Lactate. •Under aerobic conditions (i.e. when oxygen is present), the dominant glycolytic product in most tissues is Pyruvate and the pathway is known as Aerobic Glycolysis. •Under anaerobic conditions (i.e. when oxygen is depleted) as for instance during prolonged vigorous exercise, the dominant glycolytic product in many tissues is Lactate and the pathway is known as Anaerobic Glycolysis. Glycolysis Stage 1 Energy requiring (consuming) stage - ATP - ATP Glycolysis Stage 2 (Energy producing stage) 2 Molecules. + 2 ATP + 2 ATP Oxygen requiring step Pathway of Cytoplasmic Glycolysis of Glucose Special feature of Anaerobic Glycolysis in RBCs 1. RBCs contain no mitochondria. Therefore, they depend only on anaerobic glycolysis to produce 2 ATP. 2. The RBCs have the ability to form 2,3 Bisphospho- glycerate (2,3-DPG) through Rapoport- Luebering cycle using mutase enzyme. *. The presence of 2,3 DPG lowers the affinity of Hb to O2 leading to good oxygenation of tissues and formation of Rapoport-Luebering cycle pyruvate. Special Features of Anaerobic Glycolysis in RBCs Clinical significance of 2,3-DPG: 1. During storage of blood in blood banks, 2,3-DPG concentration decreases gradually to reach 0.5 mg after 10 days (normal: 4.5 mg). This lead to high O2 affinity of the stored blood which is not desirable for blood transfusion. *. As 2,3 DPG can not penetrate RBCs, addition of Inosine (a substance can penetrate erythrocytes and changed into 2,3-DPG through HMP pathway) is advisable. 2. Also, persons living at high altitudes undergo a state of low O2 affinity due to increase of 2,3-DPG. *. This disappears on returning to the Sea Level I.e. a state of normal oxygen affinity is obtained. 3. Moreover, fetal hemoglobin (HbF) binds less strongly with 2.3-DPG than adult hemoglobin (HbA) consequently it has a higher O2 affinity. This may be a source of pathogenesis in patients carrying such type of haemoglobin. Energy (ATP) Production of Cytoplasmic Glycolysis Generally, ATP Production = ATP Produced – ATP Utilized 1-Anaerobic Glycolysis: Anaerobic ATP production = 4 ATP – 2 ATP = 2 2-Aerobic Glycolysis (if oxygen get available) Aerobic aATP p)roduction == 4 + 6* (or 4 + 4*) ATP – 2 ATP = 8 (or 6) •From extra-mitochondrial oxidation of 2 NADH + H+ by respiratory chain phosphorylation in mitochondria using two special carriers for hydrogen. Carbohydrates • Serve as primary source of energy in the cell • Central to all metabolic processes Glucose Cytosol - anaerobic Hexokinase Pentose Phosphate Glucose-6-P Glc-1- phosphate Shunt glycolysis glycogen Pyruvate cytosol Pyruvate mitochondria
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