Chapter 25 Metabolism and Nutrition Copyright © John Wiley & Sons, Inc. All rights reserved. Nutrition Major nutrients Carbohydrates, lipids, and proteins Other nutrients Vitamins and minerals( & water) A diet consisting of the five food groups: grains, fruits, vegetables, meat & fish, milk products provides adequate amount of all nutrients Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolism and Nutrition A nutrient is a “food or liquid that supplies the body’s metabolic needs. Nutrients include: A necessary chemical that help regulate body processes.(such as Na+ and other minerals) A substance that provides energy (such as lipids or carbohydrates like glucose) Something that helps in growth and normal metabolism (such as vitamins) A substance that repairs or maintains body functions (such as proteins, or amino acids to make proteins) Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolism and Nutrition Metabolic reactions contribute to homeostasis by harvesting chemical energy from consumed nutrients to contribute to the body’s growth, repair, and normal functioning Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolism Metabolism denotes the sum of all body chemical reactions Catabolism is breaking down larger molecules into smaller molecules. Catabolic reactions provide more energy than they consume; they are exergonic – they liberate energy Anabolism is building larger molecules from smaller molecules. Anabolic reactions consume more energy than they produce; they are endergonic – they consume energy Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolism Metabolism is an energy-balancing act between catabolic reactions and anabolic reactions The molecule that participates most often in energy exchanges in living cells is ATP (adenosine triphosphate), which couples energy-releasing catabolic reactions to energy-requiring anabolic reactions Copyright © John Wiley & Sons, Inc. All rights reserved. ATP ATP temporarily stores and transfers energy given off in catabolic reactions and transfers it to anabolic reactions that require energy. Copyright © John Wiley & Sons, Inc. All rights reserved. Oxidation- Reduction (Redox)Reactions Chemical reactions in which electrons are exchanged as a means of transferring energy are called REDOX reactions Oxidation is the loss of electrons, Remember: OIL, RIG or hydrogen atoms Reduction is the gain of electrons, or hydrogen atoms Copyright © John Wiley & Sons, Inc. All rights reserved. REDOX Reactions Since oxidation-reduction reactions always occur together, the oxidation of glucose results in reduction of the coenzymes NAD + and FAD+ as the electrons are transferred to them Reduction, then, results in an increase in potential energy; energy taken from the oxidized substrate (glucose in our example) Copyright © John Wiley & Sons, Inc. All rights reserved. Carbohydrate Metabolism Dietary sources Starch (polysaccharide) in grains and vegetables Sugars in fruits, sugarcane, sugar beets, honey and milk Uses Glucose is the fuel used by cells to make ATP (neurons and RBCs rely almost entirely on glucose) Excess glucose is stored as glycogen or fat Dietary requirements 130 g/day- 45–60% of total calorie intake; mostly complex carbohydrates (whole grain & vegetables recommended) Copyright © John Wiley & Sons, Inc. All rights reserved. Carbohydrate Metabolism Glucose is the body’s preferred source of fuel During digestion, polysaccharides and disaccharides are hydrolyzed into the monosaccharides glucose (80%), fructose, and galactose These three monosaccharides are absorbed into the villi of the small intestine and carried to the liver ◦ hepatocytes convert galactose and fructose to glucose Copyright © John Wiley & Sons, Inc. All rights reserved. Carbohydrate Metabolism The oxidation of glucose to form ATP... Glucose (C6H12O6) + 6O2 6CO2 + 6H2O + ATP ... is known as “Cellular Respiration” and occurs in 4 steps: Glycolysis Formation of Acetyl CoA Krebs cycle Electron transport chain and oxidative phosphorylation Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular Respiration- overview Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular respiration (glucose oxidation- overview) Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular Respiration Glycolysis Anaerobic (does not require oxygen) Occurs in the cytoplasm Oxidation of one 6-carbon molecule of glucose into two 3-carbon molecules of pyruvic acid Glucose 2 pyruvic acid molecules + 2 ATP 2NADH formed Copyright © John Wiley & Sons, Inc. All rights reserved. Glycolysis Fate of pyruvic acid depends on availability of oxygen ◦ If O2 is not available pyruvic acid - converted to lactic acid ◦ If O2 is available- pyruvic acid enters mitochondria Acetyl-CoA will be formed from pyruvic acid and aerobic cellular respiration continues Copyright © John Wiley & Sons, Inc. All rights reserved. Formation of Acetyl CoA This stage is the “link” between glycolysis and Krebs citric acid cycle- occurs in mitochondrial matrix 3carbon pyruvate converted to 2 carbon acetyle group by removal of one CO2 acetyle group and coenzyme A (CoA) combined to form acetyl CoA For every glucose molecule (from two pyruvate molecules) the final products are: 2 acetyl CoA, 2 NADH, 2 CO2 Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular Respiration Krebs cycle: Completes breakdown of glucose in a mitochondrion acetyl-CoA enters the the Krebs cycle A series of oxidation reduction reactions Products of 2 turns of Krebs cycle: 4 CO2 2ATP 6NADH 2FADH2 Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular Respiration The electron transport system and oxidative phosphorylation Involves the transfer of electrons from NADH and FADH2 to the electron transport system energy released used to make ATP oxygen is the the final electron acceptor Copyright © John Wiley & Sons, Inc. All rights reserved. Cellular Respiration In the total oxidation of 1 molecule of glucose, 36-38 molecules of ATPs are generated, depending on the tissue Only 4 ATP are generated by substrate level phosphorylation (directly transferring a phosphate from one molecule to another) in glycolysis and the Krebs cycle Most of the ATP (either 32 or 34) is made by oxidative phosphorylation using the electron transport chain Copyright © John Wiley & Sons, Inc. All rights reserved. Glucose Storage - Glycogenesis If glucose is not needed immediately for ATP production, glucose is stored as glycogen, a polysaccharide that is the only stored form of carbohydrate in our bodies Insulin hormone stimulates glycogenesis 75% glycogen stored in skeletal muscle, rest in liver cells Copyright © John Wiley & Sons, Inc. All rights reserved. Glucose Release- Glycogenolysis Glycogenolysis When cells require ATP, stored glycogen is broken down into glucose and released into the blood to be transported to cells Only liver can release glucose from breakdown of stored glycogen into blood ( skeletal muscles lack the enzyme phosphatase) Glycogenolysis stimulated by glucagon, epinephrine Copyright © John Wiley & Sons, Inc. All rights reserved. Glycogenesis & Glycogenolysis Copyright © John Wiley & Sons, Inc. All rights reserved. Making Glucose- Gluconeogenesis Gluconeogenesis is the process of orming “new” glucose from non-carbohydrate sources in the liver Gluconeogenesis occurs on a large scale during fasting, or eating a low carbohydrate diet Lactic acid, amino acids, and the glycerol (from triglycerides) are used to form glucose molecules or pyruvic acid Gluconeogenesis is stumulated by cortisol and glucagon Copyright © John Wiley & Sons, Inc. All rights reserved. Gluconeogenesis Copyright © John Wiley & Sons, Inc. All rights reserved. Lipids Dietary sources Triglycerides- most abundant dietary lipids Saturated fats- FA’s have single carbon-carbon bonds-- in meat, dairy foods, Unsaturated fats- FA’s have some double -- in seeds, nuts, olive oil and vegetable oils Cholesterol in egg yolk, meats, organ meats, shellfish, milk products- liver produces major amount Fatty acids linoleic acid & linolenic acid in vegetable oils (essential fatty acids) must be ingested Dietary requirements: Should be 30% or less of total caloric intake Copyright © John Wiley & Sons, Inc. All rights reserved. Lipoproteins & lipid transport Most lipids are transported in the blood in combination with proteins as lipoproteins In general lipoproteins have: An outer shell that is made hydrophilic due to polar proteins (plus amphipathic phospholipids) An inner core that is hydrophobic - a place where mostly triglycerides are transported Copyright © John Wiley & Sons, Inc. All rights reserved. Classes of Lipoproteins Chylomicrons (2 % protein, 85% TGs, also cholesterol, phospholipids) form in intestinal epithelial cells Transport dietary fat Enter lacteals, carried by lymphatic system to blood ◦ Lipases of blood vessel endothelial cells release fatty acids from the chylomicron ◦ Taken up by adipose & muscle cells ◦ liver processes the remnants of chylomicrons VLDLs (10% protein, 50% TGs, phospholipids & cholesterol ) VLDLs form in the liver Transport triglycerides from liver to fat cells converted to LDLs Copyright © John Wiley & Sons, Inc. All rights reserved. Classes of Lipoproteins LDLs (25% protein, 50% cholesterol) --- “bad cholesterol” carry 75% of total cholesterol in blood – transport it to to body cells LDL enters cells via LDL receptors HDLs (40%, protein, 20% cholesterol) --- “good cholesterol” carry cholesterol from cells to liver for elimination in bile Copyright © John Wiley & Sons, Inc. All rights reserved. Cholesterol There are two sources of cholesterol in the body: food we eat and synthesis in the liver For adults, normal blood cholesterol are: Total cholesterol- under 200 mg/dl LDL under 130 mg/dl HDL over 40 mg/dl. Normally, triglycerides are in the range of 10-190 mg/dl. Copyright © John Wiley & Sons, Inc. All rights reserved. Triglyceride Storage Adipose tissue removes fatty acids from chylomicrons and VLDLs and stores them as triglycerides in: 50% subcutaneous tissue, around kidneys, in omenta, genital area, between muscles and other areas They are catabolized and mobilized constantly throughout the body. Copyright © John Wiley & Sons, Inc. All rights reserved. Lipid Metabolism The conversion of glucose or amino acids into triglycerides is called lipogenesis. Occurs when we consume more calories than are needed to satisfy ATP needs Insulin stimulates lipogenesis amino acids ---acetyl coA---fatty acids---TGs glucose---acetyl coA---fatty acids---TGs Copyright © John Wiley & Sons, Inc. All rights reserved. Lipid Metabolism Lipolysis refers to breakdown of TGs to glycerol and fatty acids Glycerol can be converted into glucose, or pyruvic acid In beta oxidation of fatty acids, carbon atoms are removed in pairs from fatty acid chains-- acetyl coenzyme A formed--enters the Krebs cycle. Lipolysis can occur under the action of epinephrine, norepinephrine, thyroid hormones and cortisol Copyright © John Wiley & Sons, Inc. All rights reserved. Lipid Metabolism Ketogenesis : occurs as a part of normal fatty acid catabolism From acetyle coA the liver forms acetoacetic acid which can then be converted to beta-hydroxybutyric acid and acetone ( ketone bodies) Ketogenesis is a normal part of fat breakdown, but an excess will cause a metabolic acidosis Copyright © John Wiley & Sons, Inc. All rights reserved. Pathways of lipid metabolism Copyright © John Wiley & Sons, Inc. All rights reserved. Proteins Dietary sources Animal proteins contain greatest amounts of essential amino acids- eggs, milk, fish, meats Beans, nuts, and cereals lack some essential amino acids Daily intake- 0.8 g per kg body weight Uses Structural proteins: keratin, collagen, elastin, muscle proteins Functional proteins: enzymes, some hormones Copyright © John Wiley & Sons, Inc. All rights reserved. Proteins During digestion, proteins are hydrolyzed into amino acids Amino acids are absorbed by the blood capillaries of villi and enter the liver via the hepatic portal vein Amino acids, under the influence of growth hormone and insulin, enter body cells by active transport. Inside cells, amino acids are synthesized into proteins Amino acids may also be stored as fat or glycogen( after conversion to glucose) or used for energy Essential amino acids are the 10 amino acids that can’t be synthesized by the body ( have to be taken in diet) Copyright © John Wiley & Sons, Inc. All rights reserved. Protein Catabolism Liver cells convert amino acids into substances that can enter the Krebs cycle to produce ATP First deamination removes the amino group (NH2) ◦ converts amino groups to ammonia (NH3) & then urea ◦ urea is excreted in the urine In liver cells amino acids can also be converted into: Glucose ( gluconeogenesis) fatty acids ( lipogenesis) ketone bodies ( ketogenesis) Copyright © John Wiley & Sons, Inc. All rights reserved. Protein Anabolism Involves the formation of peptide bonds between amino acids to produce new proteins. ◦ Structural proteins: keratin, collagen, elastin, muscle proteins ◦ Functional proteins: enzymes, hemoglobin, antibodies, some hormones Stimulated by human growth hormone, testosterone, thyroxine, and insulin. Protein synthesis carried out on the ribosomes of almost every cell in the body, directed by the cells DNA and RNA. Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolic Adaptations During the absorptive state ingested nutrients entering the blood stream and glucose is readily available fot ATP production During the postabsorptive state absorption of nutrients from GI tract has been completed and energy needs must be met by fuels in the body An average meal requires about 4 hours for complete absorption, and given three meals a day, the body spends about 12 hours of each day in the absorptive state. Copyright © John Wiley & Sons, Inc. All rights reserved. The Absorptive State Soon after a meal glucose, amino acids, and triglycerides (as chylomicrons) enter the blood There are 2 metabolic hallmarks of this state: Glucose is oxidized to produce ATP in all body cells Any excess fuel molecules are stored in hepatocytes, adipocytes, and skeletal muscle cells Pancreatic beta cells begin to release insulin Storage: nutreints stored as glycogen or triglycerides Copyright © John Wiley & Sons, Inc. All rights reserved. Regulation of Metabolism During the Absorptive State Rise in blood glucose concentration stimulate insulin release from pancreatic beta cells. Insulin’s functions promotes entry of glucose into skeletal muscle & adipose tissue stimulates storage of glucose as glycogen in liver & muscle enhances synthesis of triglycerides in adipose tissue & liver Promotes entry of amino acids into cells & protein synthesis stimulates protein synthesis along with thyroid & growth hormone Copyright © John Wiley & Sons, Inc. All rights reserved. The Postabsorptive State About 4 hours after the last meal absorption in the small intestine is nearly complete and blood glucose levels start to fall. The main metabolic challenge at this point is to maintain normal blood glucose levels (70 to 110 mg/100 ml) As blood glucose levels decline, glucagon secretion increases ◦ Blood glucose levels are sustained by: ◦ the breakdown of liver glycogen & gluconeogenesis using lactic acid and/or amino acids ◦ lipolysis Copyright © John Wiley & Sons, Inc. All rights reserved. The Postabsorptive State Cells use alternative fuel sources (conserves glucose for brain & RBCs) ◦ fatty acids from fat tissue fed into Krebs as acetyl CoA ◦ lactic acid produced anaerobically during exercise ◦ ketone bodies by heart & kidney ◦ Homeostasis of blood glucose concentration is especially important for the nervous system and red blood cells. Copyright © John Wiley & Sons, Inc. All rights reserved. Regulation of Metabolism During the Postabsorptive State The most important hormone is glucagon. stimulates gluconeogenesis & glycogenolysis within the liver Hypothalamus detects low blood sugar- increases sympathetic output: release of norepinephrine & epinephrine ◦ stimulates glycogen breakdown & lipolysis ◦ raises glucose & free fatty acid blood levels Copyright © John Wiley & Sons, Inc. All rights reserved. Basal Metabolic Rate The metabolic rate is the overall rate at which metabolic reactions use energy. Basal metabolic rate (BMR) is measured with the body in a quiet, fasting condition The BMR is 1200–1800 Cal/day in adults, or about 24 Cal/kg of body mass in adult males and 22 Cal/kg in adult females Copyright © John Wiley & Sons, Inc. All rights reserved. Body Temperature Body temperature reflects the balance between heat production and heat loss homeostatic mechanisms maintain a normal range for internal (core) body temperature at 37°C (98.6°F) Peripheral tissues can be much cooler (“shell temperature 1-6°C lower) ◦ Body temperature is maintained by hormonal regulation of the BMR, and sympathetic nervous system stimulation Copyright © John Wiley & Sons, Inc. All rights reserved. Metabolism & Heat Production Factors that affect metabolic rate and thus the production of body heat exercise increases metabolic rate as much as 15 times thyroid hormones increase BMR sympathetic nervous system’s release of epinephrine & norepinephrine increases metabolic rate higher body temperature increases metabolic rate ingestion of food raises increases metabolic rate by 10- 20% Copyright © John Wiley & Sons, Inc. All rights reserved. The Hypothalamic Thermostat The body’s thermostat is a group of neurons in the hypothalamus that receives impulses from thermoreceptors scattered throughout the body Nerve impulses from the thermostat propagate to the heat-losing center and the heat-promoting centers of the hypothalamus Several negative feedback loops work to raise body temperature when it drops too low or to lower body temperature Copyright © John Wiley & Sons, Inc. All rights reserved. Thermoregulation If the core temperature declines, skin blood vessels constrict and thyroid hormones and catecholamines (epinephrine and norepinephrine) are released. Cellular metabolism increases and shivering my ensue If core body temperature rises, blood vessels of the skin dilate, sweat glands are stimulated, and the metabolic rate is lowered Copyright © John Wiley & Sons, Inc. All rights reserved. Regulation of Food Intake Nuclei in the hypothalamus regulate hunger & satiety The brain receives signals from: Neural signals from the digestive tract ( via vagus nerve) Rising blood levels of glucose, amino acids, fatty acids indicate fullness Hormones ◦ Insulin & leptin (released from fat cells) suppress hunger ◦ glucagon stimulates hunger To a lesser extent, body temperature (increase inhibits eating) and psychological factors Copyright © John Wiley & Sons, Inc. All rights reserved.