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general concepts and characteristics of metabolic pathways. Digestion and absorption of dietary carbohydrates Pathways of glucose metabolism: glycolysis Pentose phosphate shunt Gluconeogenesis Glycogenolysis, glycogenesis Galactose and fructose metabolism Glycogen storage disease Inborn errors of glucose metabolism Regulation of glucose metabolism. III-I Metabolism III-II Carbohydrate metabolism III-III Digestion and absorption of dietary fats. Biosynthesis and degradation of fatty acids, TCA cycle and biological oxidation phospolipids and triacylglycerols Biosynthesis of cholesterol, chemistry and Protein turnover and amino metabolism of lipoproteins. acid metabolism Hyperlipoproteinemias Lipid storage disease. Regulation of the metabolic pathways Ketone bodies: their synthesis, utilization and conditions leading to ketoacidosis, III-IV III-V III-VI Lipid metabolism (a) Interlinks between carbohydrate, lipid and amino acid metabolic pathways. (b )Cellular compartment and cooperation (c) Organ interrelationships in metabolism, (d) Metabolic adaptation in the fed state, fasting and prolonged starvation. (e) Blood glucose regulation, and its impairment in diabetes mellitus. (f) Metabolic derangements and adaptations in diabetes mellitus. (a) Digestion and absorption of dietary protein (b) General reactions, transamination, its metabolic and diagnostic significance (c) Disposal of amino acid nitrogen and detoxication of urea (d) Metabolic fate of amino acid carbon skeleton (e) Sulphur containing amino acids (f) In born errors of branched chain and aromatic amino acids (g) Important amino acid derivatives. III-I Metabolism III-II Carbohydrate metabolism III-III Lipid metabolism III-IV Review and Summarize TCA cycle and biological oxidation III-V Protein turnover and amino acid metabolism III-VI Regulation of the metabolic pathways III-VI Regulation of the metabolic pathways 1. Interlinks between carbohydrate, lipid and amino acid metabolic pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Key intermediates connect pathways. Energy-rich compounds are converted mutually to a great extent. Carbohydrate/fat are priority-ranked in mobilizing. Key enzymes in pathways are regulated in similar way. Energy charge regulates whole status of metabolism. The major pathways of fuel metabolism in mammals Only a few tissues, such as liver, can carry out all the reactions illustrated above. metabolic pathways for glucose-6-phosphate in the liver amino acids amino acids Summary of metabolic fates of pyruvate Overview of metabolism Important reactions of intermediary metabolism regulated by phosphorylation of enzyme Many reactions in metabolism are controlled by the energy status of the cell. High concentrations of ATP inhibit the relative rates of a typical ATP-generating (catabolic) pathway and simulate the typical ATP-utilizing (anabolic) pathways III-VI Regulation of the metabolic pathways 1. Interlinks between carbohydrate, lipid and amino acid metabolic pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Pathways are located in different places in the cell. Molecules are transported between subcellular parts according to the demand cytosol protein degradation glycogen synthesis glycolysis endoplasmic reticulum TCA β-oxidation urea cycle mitochondria aerobic oxidation of carbohydrate ketone bodies amino acids catabolism fatty acid synthesis pentose phosphate pathway lysosome protein degradation Transfer of the starting materials of lipid anabolism from the mitochondrion to the cytosol. 1.PEP carboxykinase in mitochondrion 2.PEP carboxykinase in cytosol Transfer of the starting materials of gluconeogenesis from the mitochondrion to the cytosol. III-VI Regulation of the metabolic pathways 1. Interlinks between carbohydrate, lipid and amino acid metabolic pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Tissues –specific metabolism Metabolism is cooperated between tissues. Only a few tissues, such as liver, can carry out all the reactions illustrated in slide 7. Specialized metabolic functions of mammalian tissues Low blood glucose will result in brain dysfunction. Body’s central metabolic clearinghouse Mitochondria occupy up to 40% of cytoplasmic space. atherosclerosis , insufficient O2 supply. the major fuelmetabolizing organs Artery & Vein Body’s central metabolic clearinghouse The portal circulation The portal vein drains almost all of the blood from the digestive tract and empties directly into the liver. This circulation of nutrient-rich blood between the gut and liver is called the portal circulation. It enables the liver to remove any harmful substances that may have been digested before the blood enters the main blood circulation around the body—the systemic circulation. There are two cycles between muscle and liver. The Cori Cycle The Glucose-Ala Cycle Mechanisms of communication between four major tissues III-VI Regulation of the metabolic pathways 1. Interlinks between carbohydrate, lipid and amino acid metabolic pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Living things coordinate their activities at every level of their organization through complex signaling systems involving chemical messengers known as hormones. In higher animals, endocrine glands synthesize and release hormones, which are carried by the bloodstream to their target cells. The human endocrine systems secretes a wide variety of hormones that enable the body to maintain homeostasis, respond to wide variety of external stimuli , follow various cyclic and developmental programs Endocrine signaling Opposing actions of insulin and glucogon plus epinephrine Insulin causes an increase in glucose uptake, mainly in muscle cells and adipocytes, stimulates storage of glucose as glycogen, mainly in liver cells. Glucagon acts mainly on liver cells to stimulate glycogen degradation. III-VI Regulation of the metabolic pathways 1. Interlinks between carbohydrate, lipid and amino acid metabolic pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Feed/Fast largely effect the energy metabolism in different organs. The hormones will respond to the blood glucose and then regulate by their own ways. Intertissues relationships in the absorptive state Insulin-dependent transport system Intertissue relationship during starvation absorbtive starvation starvation absorbtive starvation absorbtive starvation absorbtive Key concept map for feed/fast cycle III-VI Regulation of the metabolic pathways 1. Interlinks between Carbohydrate, lipid and amino acid metabolism pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. Regulation of Blood Glucose Blood glucose levels are not constant—they rise and fall depending on the body's needs, regulated by hormones. This results in glucose levels normally ranging from 70 to 110 mg/dl. The blood glucose level can rise for three reasons: diet, breakdown of glycogen, or through hepatic synthesis of glucose. Eating produces a rise in blood glucose, the extent of which depends on a number of factors such as the amount and the type of carbohydrate eaten, the rate of digestion, and the rate of absorption. The liver is a major producer of glucose —it releases glucose from the breakdown of glycogen and also makes glucose from intermediates of carbohydrate, protein, and fat metabolism. The liver is also a major consumer of glucose and can buffer glucose levels. It receives glucose-rich blood directly from the digestive tract via the portal vein. The liver quickly removes large amounts of glucose from the circulation so that even after a meal, the blood glucose levels rarely rise above 110 mg/dl in a non-diabetic. Glucose homeostasis blood glucose Aspects of the control of blood glucose levels by pancreatic secretion of insulin and glucagon Twenty-four-hour plasma profiles in normal and non-insulin-dependent diabetes III-VI Regulation of the metabolic pathways 1. Interlinks between Carbohydrate, lipid and amino acid metabolism pathways. 2. Cellular compartment and cooperation 3. Organ interrelationships in metabolism, 4. Hormonal control of fuel metabolism 5. Metabolic adaptation in the fed state, fasting and prolonged starvation. 6. Blood glucose regulation, and its impairment in diabetes mellitus. 7. Metabolic derangements and adaptations in diabetes mellitus. When the amount of glucose in the blood increases, e.g., after a meal, it triggers the release of the hormone insulin from the pancreas. Insulin stimulates muscle and fat cells to remove glucose from the blood cells to breakdown glucose, releasing its energy in the form of ATP the liver and muscle to store glucose as glycogen adipose tissue to store glucose as fat cells to use glucose in protein synthesis causing the blood sugar level to decrease to normal levels Diabetes mellitus is characterized by abnormally high levels of sugar (glucose) in the blood. In people with diabetes, blood sugar levels remain high. This may be because insulin is not being produced at all, not made at sufficient levels, not as effective as it should be. The most common forms of diabetes are type 1 diabetes (5%), which is an autoimmune disorder, and type 2 diabetes (95%), which is associated with obesity. Gestational diabetes is a form of diabetes that occurs in pregnancy, and other forms of diabetes are very rare and are caused by a single gene mutation. Insulin resistant Metabolic changes in diabetic ketoacidosis. How will you review Part III? List all the Q & A. Ponder all the Q. Read all the sentences with underline. Come from different parts Part I (a,b,c) 8 points Part I (d) & II 17 points Part III 38 points Part IV-VII 37 points Biochemistry Examination 70% Single best answer (from multiple choice questions) (1X10) Fill in the blanks (1X40) True/False (1X20) Essay questions (5X6) 100X 70% Midterm Test (or assignment) 30 %