Carbohydrate Metabolism Lecture Notes PDF

# Lecturer 1: Introduction to Carbohydrate Metabolism ## Badr Institute of Science and Technology ### Metabolism * **Metabolism:** the sum of all the chemical changes occurring in a cell, a tissue, or the body. * Most pathways can be classified as either catabolic (degradative) or anabolic (...

# Lecturer 1: Introduction to Carbohydrate Metabolism ## Badr Institute of Science and Technology ### Metabolism * **Metabolism:** the sum of all the chemical changes occurring in a cell, a tissue, or the body. * Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic). ### **Catabolic Reactions** * Catabolic reactions break down complex molecules, such as proteins, polysaccharides, and lipids, to a few simple molecules, for example, CO2, NH3 (ammonia), and water. ### **Anabolic Pathways** * Anabolic pathways form complex end products from simple precursors, for example, the synthesis of the polysaccharide, glycogen, from glucose ### Catabolic Pathways - Catabolic reactions serve to capture chemical energy in the form of adenosine triphosphate (ATP) from the degradation of energy-rich fuel molecules. - Catabolism also allows molecules in the diet (or nutrient molecules stored in cells) to be converted into building blocks needed for the synthesis of complex molecules. ### Anabolic Pathways - Anabolic reactions combine small molecules, such as amino acids, to form complex molecules, such as proteins. - Require energy (endergonic), which is generally provided by the breakdown of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi). - Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH. ## Sources of Glucose to Human Body Glucose can be obtained from three primary sources: ### **Carbohydrate in Diet:** - Carbohydrates are sources for glucose of the body after meals. - Excess glucose is stored in the form of glycogen in liver & skeletal muscles. ### Sources of Glucose of Carbohydrate Diet 1. **Free Monosaccharides:** mainly glucose & fructose (Fructose is converted into glucose in liver) 2. **Disaccharides:** * Sucrose (glucose & fructose) * Lactose (glucose & galactose) * Maltose (glucose & glucose) * They are digested into monosaccharides (glucose, fructose & galactose) in the intestine. Fructose & galactose are converted into glucose in the liver. 3. **Polysaccharides:** * Starch (plant source e.g. rice, potato, flour) * Glycogen (animal source) * They are digested into glucose in the GIT. ## Digestion and Absorption * Digestion of CHO is accomplished by the enzymes of digestive fluids, saliva, pancreatic juice and intestinal juice. * **1. Mouth:** salivary glands secrete saliva * Saliva contains: a- amylase (ptyalin), water 99.5% and glycoprotein. * PH of a- amylase = 5.8 – 7.1 less than 4.0 is in active * **2. Stomach:** no digestion is seen in stomach, amylase is in active, Because the PH of stomach (1 - 2 ) very acidic. * **3. Small intestine:** it is the major site of digestion of CHO, pancreatic amylase. . * The optimum PH of amylase = 7.1 * **intestinal mucosal** (Brush Border) * mucosal cell membrane – bound enzymes, the site where disaccharides hydrolyze. | | | | | | :------ | :----- | :------------- | :------------- | | Maltose | maltase | glucose + glucose | | | Sucrose | sucrase | glucose + fructose | | | Lactose | lactase | glucose + galactose | | ## Digestion of Carbohydrates A diagram showing the digestion of carbohydrates from the mouth to the small intestine. ## Carbohydrate to Blood A diagram showing the breakdown of a carbohydrate meal from the mouth to the blood stream. ## Absorption of Carbohydrates - **1. Transport into epithelial cells (of the villi)** glucose and galactose are transported by active transport, while fructose is transported by facilitated diffusion. - **2. Transport from epithelial cells into the blood stream is by facilitated diffusion.** ### **Fate of glucose after absorption** - **In the liver, glucose undergoes variety of chemical changes depending upon the physiological need of the body.** ## Sources of Glucose to Human Body: Glucose can be obtained from three primary sources: - **Carbohydrate in Diet:** Carbohydrates are sources for glucose of the body after meals. - **Excess glucose is stored in the form of glycogen in liver & skeletal muscles.** - **Glycogen degradation (Glycogenolysis):** - **Glycogen (synthesized from glucose molecules) is stored in liver & skeletal muscles.** - **In cases of fasting, liver glycogen is degraded to yield glucose for blood.** - **In cases of muscular exercise, muscle glycogen is degraded to secure glucose for muscles as a source of energy.** ## Critical importance of glucose A constant source of GLUCOSE is an absolute requirement for human life as it is: 1. **Preferred energy of the brain** 2. **Required energy source for cells with no or few mitochondria (as RBCs)** 3. **Essential source of energy for exercising muscles (substrate for anerobic glycolysis)** ## Fate of glucose after absorption * **1. Body need for energy:** glucose oxidized completely to CO2, H2O and energy by (glycolysis and citric acid cycle). * **2. Excess glucose may be converted to glycogen, deposit in liver, muscle tissues By (glycogenesis).** * **3. To maintain glucose blood level, liver glycogen reconverted to glucose enters blood By (glycogenolysis).** * **4. excess glucose after conversion to glycogen, convert to fatty acids stored in adipose tissue as triglycerides (lipogenesis).** * **5. small amounts of glucose may be utilized for the synthesis of ribose and deoxyribosee for synthesis of nucleic acids.** * **6. in muscle contraction, only partial degradation of glucose may take place, resulting in formation of lactic acid disposed off by the liver.** ## Glucose Transport into Cells * Glucose cannot diffuse directly into cells, but enters by one of two transport mechanisms: 1. Na+-independent, facilitated diffusion transport system 2. Na+-monosaccharide cotransporter system. ## Types of Glucose transporters - **1- Na+-independent facilitated diffusion transport:** Transport occurs with concentration gradient, No require for energy (i.e. ATP). It is conducted by a group of at least 14 glucose transporters (GLUT-1 to 14) ## Glut proteins have specialized functions * In facilitated diffusion, glucose movement follows a concentration gradient, that is, from a high glucose concentration to a lower one. * For example, GLUT-1, GLUT-3, and GLUT-4 are primarily involved in glucose uptake from the blood. * In contrast, GLUT-2, which is found in the liver and kidney, can either transport glucose into these cells when blood glucose levels are high, or transport glucose from these cells when blood glucose levels are low (for example, during fasting). ## Types of Glucose transporters - **2- Na+-monosaccharide co-transporter system:** Glucose is transported against a concentration gradient from low glucose concentrations outside the cell to higher concentrations within the cell. * Energy-requiring process ## 2. Na+-monosaccharide cotransporter system * This is an energy-requiring process that transports glucose "against" a concentration gradient—that is, from low glucose concentrations outside the cell to higher concentrations within the cell. * This system is a carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na+, which is transported into the cell at the same time. * The carrier is a sodium-dependent-glucose transporter or SGLT. * This type of transport occurs in the epithelial cells of the intestine and renal tubules. ## Glut proteins are tissue spesific The glucose transporters display a tissue-specific pattern of expression. For example, * GLUT-1 is abundant in erythrocytes and blood brain barrier, but is low in adult muscle, * GLUT-2 is present in liver and kidney (GLUT-2 is also found in pancreatic β cells) * GLUT-3 is the primary glucose transporter in neurons. * GLUT-4 is abundant in adipose tissue and skeletal muscle. ## Glucose Transporter Table | Transporter | Tissues | Type of transport | Notes | Sensitive to insulin? | | :---------- | :---------------------------------------- | :---------------- | :------------------------------------------------------------------------------------------------------------------------------------------------------ | :--------------------- | | SGLT | Renal tubules, intestinal epithelia (apical membrane) | Secondary active transport | Responsible for the absorption (intestine) and reabsorption (renal tubule cells) of glucose. | No | | GLUT1 | Pancreatic beta cells, hepatocytes | Facilitated diffusion | Pancreatic beta cells: important for gauging blood glucose levels in humans. | No | | GLUT2 | Pancreatic beta-cells, hepatocytes, intestinal epithelium, kidney | Facilitated diffusion | Hepatocytes: bi-direction transport of glucose when influenced by hormones, such as thyroid hormone. | No | | | | | Hepatocytes: important for the bi- directional transport of glucose with regards to hepatic glucose metabolism. | | | GLUT3 | CNS | Facilitated diffusion | Very high affinity for glucose. | No | | GLUT4 | Skeletal muscle, cardiac muscle, adipose tissue | Facilitated diffusion | Expression regulated by insulin. | Yes | *Most transporters are found in a variety of tissues, but are expressed in higher concentrations in specific cell-types. ## Glucose transporters (GLUT) A diagram illustrating the facilitated transport of glucose through a cell membrane. - **In the diagram, the glucose transporter is in state 1 when glucose is outside the cell. The transporter moves to state 2 when glucose is inside the cell.**