NTD2101 LC1-2 Nutritional Biochemistry PDF

Nutritional Biochemistry Assoc. Prof. Dr. Bestenur YALÇIN During This Semester... About Grading… Presentation-Project %20 Midterm %40 Final Exam %40 Objectives … This course is designed to provide a foundation for many scientific fields of study....

Nutritional Biochemistry Assoc. Prof. Dr. Bestenur YALÇIN During This Semester... About Grading… Presentation-Project %20 Midterm %40 Final Exam %40 Objectives … This course is designed to provide a foundation for many scientific fields of study. Course topics cover the organic structures of living systems and basic principles and applications. The aim of this course is to examine the foods in nutrition from a biochemical perspective, to learn theoretically the basic topics of how foods are metabolized, taken up by cells and converted into energy, and the use of energy. Students who can successfully complete this course; 1) Will have basic knowledge in the field of nutritional biochemistry. 2) Will learn theoretically the basic topics related to nutrition in biochemistry. 3) Will be able to research, understand, and evaluate scientific literature. 4) Will be able to perceive and interpret the metabolic events that occur during the digestion of food as a whole. 5) Will be able to determine the five classes of polymeric biomolecules and their monomeric structural units. 6) Will have knowledge to examine the metabolism and functions of macronutrients and micronutrients. 7) Will develop the ability to use general information about the functions and metabolism of hormones. Nutritional Biochemistry Project Topics 1. Bioenergetics and the role of ATP in cellular energy metabolism 2. Electron transport chain and its importance in oxidative phosphorylation 3. Chemiosmotic model: Mechanisms and applications in metabolism 4. Monosaccharides: Structure, chemical properties, and their metabolic significance 5. Mechanisms of carbohydrate digestion and absorption in the human body 6. Glycolysis and its role in energy production and metabolic pathways 7. The Citric Acid Cycle (CAC) and its integration with other metabolic pathways 8. Alcohol metabolism: Pathways and impact on human health 9. Hormonal regulation of carbohydrate metabolism under normal and pathological conditions 10. Lipid digestion, absorption, and metabolism: From dietary intake to energy production 11. Ketone body production and its role in metabolism during fasting or low carbohydrate diets Nutritional Biochemistry Project Topics 12. Cholesterol metabolism and its regulation in relation to cardiovascular health 13. Hormonal regulation of lipid metabolism and its impact on adipose tissue 14. Protein structure and the significance of peptide bonds in biological systems 15. Metabolic disorders related to protein digestion and absorption: Case studies 16. Disaccharides: Structure, digestion, and their role in human nutrition 17. The role of fermentation in carbohydrate metabolism and its applications in food production 18. Hormonal regulation of protein metabolism: Mechanisms and health implications 19. Energy homeostasis: Mechanisms of appetite control and metabolic regulation 20. Steroid hormones: Biosynthesis, mechanisms of action, and their effects on metabolism Projects… Last three weeks of the semester were planned for project submissions and presentations. You gonna submit a detailed document (at least ten pages) related with your project topic and you are going to prepare a powerpoint presentation summarizing your project. Each student is going to take the responsibility of a part of that presentation and he/she is gonna make a brief speech. Projects are going to constitute 20% of NTD2101. Printed project document and your presentation is gonna be graded out of 15 and out of 5, respectively. Project grading and evaluations …… gonna be online Nutrition? Nutrition is defined as the intake and optimal utilization of nutrients from external sources to ensure growth and development, sustain life functions, and maintain a healthy life. Proper nutrition refers to the intake of the right nutrients in the right amounts for health maintenance. It is more appropriate to use the term PROPER NUTRITION instead of good nutrition. 7 In proper nutrition; ⚫ What nutrients should be consumed? ⚫ What is the biological role of these nutrients? ⚫ What is the minimum daily amount required to fulfill this biological function? 8 Biochemistry? Biochemistry (Chemistry of Life) is the branch of science that studies the structure, organization, and function of living organisms at the molecular level. It is an interdisciplinary and multidisciplinary field that benefits applied areas such as medicine, pharmacy, nutrition, agriculture, food technology, toxicology, and veterinary science. All biochemical reactions occur under conditions suitable for life. 4 Living Organisms? Living organisms are entities that undergo a specific life cycle, exhibit growth, development, and reproduction capabilities, and sustain these processes by obtaining and utilizing energy from their environment. Throughout this process, a living organism remains in a state of maximum disequilibrium. Life can be described as a flow from maximum disequilibrium towards equilibrium. 10  Cell? A cell can be defined as: An isothermal structure made of organic molecules that conducts numerous chemical reactions using its own organic catalysts. Operates under the principle of maximum efficiency, Derives free energy from its surroundings, Has the ability to replicate itself using a coding system. 11 Chemical Composition of Living Organisms The chemical composition of the human body was first described in 1859. The organism is composed of: 60-65% water, 30-35% organic materials, The rest are inorganic substances. The most abundant elements in living organisms, which make up 98% of the structure, are: Carbon (C), Oxygen (O), Hydrogen (H), Nitrogen (N), Phosphorus (P), and Sulfur (S). 7  Elements in Living Organisms - Common and Essential: C, N, O, P, S, H (~99%) - Common and Essential: Na, Mg, K, Ca, Fe - Trace but Essential: Mn, Fe, Co, Cu, Zn - Trace but Essential for Some Organisms: V, Cr, Mo, B, Al, Ga, Sn, Si, As, Se, I  Trace elements represent a very small portion of the human body weight, but all of them are indispensable for life because they are essential for the functions of specific proteins, including enzymes. Examples: Fe, I, P, S, Cu, Zn, etc. For example, the oxygen-carrying capacity of the hemoglobin molecule is definitely dependent on four iron ions, which constitute only 0.3% of its mass. The concentrations of 14 serum trace elements, namely iron (Fe), manganese (Mn), copper (Cu), lead (Pb), zinc (Zn), arsenic (As), rubidium (Rb), chromium (Cr), selenium (Se), cobalt (Co), strontium (Sr), vanadium (V), molybdenum (Mo), cadmium (Cd), were determined by high-resolution inductively coupled plasma mass All organic molecules in living organisms are derived from simple molecules, especially carbon dioxide, water, and atmospheric nitrogen. The 4 most abundant elements in the structure of organic molecules in living things (CHON); Carbon Hydrogen Oxygen Nitrogen The tetrahedral feature of the carbon atom allows the formation of compounds in a wide variety of conformations. 15 Biochemistry from the origin of organic chemistry… Why carbon……. Carbon atoms can form strong bonds with other carbon atoms to create rings and chains. Additionally, C forms strong bonds with H, N O, and S. ‘Life' is composed of organic molecules, which are C-based molecules. “Life” is created by organic compounds. Distribution percentages of elements and biomolecules forming the human body Elements % Biomolecules % Carbon 50 Protein 17 Oxygen 20 Lipid 14 Hydrogen 10 Carbonhydrate 1,5 Nitrogen 8,5 Water 60-65 Calcium 4 Minerals 6,1 Phosphorus 2,5 Potassium 1 17 The Hierarchical Structure of Living Organisms There is a hierarchical arrangement from atoms to cells: Atoms → Biomolecules → Macromolecules → Supramolecules → Organelles → Cells → Tissues → Organisms. An example at the molecular level: Atoms (C, H, O, N, S) → Amino acids (biomolecules) → Proteins (macromolecules) → Nucleoproteins (supramolecules).  Nutrients are classified into two categories: 1. Macronutrients: Carbohydrates, lipids, proteins, and macrominerals (Ca, P, Na, K, Cl, Mg, S). These are required in grams per day. 2. Micronutrients: Vitamins and minerals (trace and ultra- trace elements). These are required in milligrams or micrograms per day. Macronutrients provide energy and form tissues and other necessary compounds, while micronutrients assist in body functions and help regulate various biochemical reactions. 19 Essential vs Non-Essential Nutrients Essential nutrients are compounds that cannot be synthesized by the human body and must be obtained through diet. These include: Essential amino acids Essential fatty acids, All water-soluble vitamins, Fat-soluble vitamins (A, E, K, and D, especially for children and those living in areas with little sunlight), Minerals (macro, trace, and ultra-trace elements). 20 Functions of Nutrients: Provide energy, Replace structural components of the body, Serve as sources for synthesizing dynamic endogenous molecules, Participate in biochemical reactions as coenzymes. 21  Daily Nutrient Requirements chance according to; Age, Lifestyle, Gender. For example: Children require more nutrients than adults. Men typically require more nutrients than women. During pregnancy and lactation, nutrient needs increase by 20-30%. Physical activity also increases nutrient requirements. 22 For individuals with a sedentary lifestyle, the average daily energy expenditure is around 2500-2700 kcal. For those performing moderate physical activity, the requirement is around 3000 kcal, while for individuals doing heavy physical labor, it ranges from 3500-4000 kcal. In conditions where environmental temperature is low or high, additional energy is expended to 23 maintain the body’s optimal temperature. Basal Metabolism Basal metabolism refers to the essential life-sustaining processes (such as respiration, blood circulation, ion transport, and maintaining body temperature) that occur in a state of complete rest. Approximately 50% of the energy from basal metabolism is used for ion transport into and out of cells. The remaining energy is spent on muscle tone, breathing, heartbeats, and maintaining body 24 temperature. Basal metabolism is measured 12 hours after the last meal. Basal Metabolic Rate (BMR) The energy required for basal metabolism is proportional to a person's lean body mass and body surface area. For basal metabolism: Women require 1400-1670 kcal/day, Men require 1600-2000 kcal/day. 25  Nutritional Science 1. The nutrients taken into the body, their contents, and the daily amounts required. 2. The digestion, absorption, and metabolism of these nutrients. 26 Metabolism: Two Subgroups ⚫ Anabolism (synthesis): ⚫ Catabolism (breakdown): Aim of the catabolism; Energy (ATP), Reducing power (NADPH), Essential building blocks. The purpose of anabolism is to synthesize structural and functional biomolecules and macromolecules. During syntheses, ATP and NADPH obtained from catabolic reactions are used. 19 Nutrients Nutrients are substances in food that are essential for life and health. They include: Carbohydrates Lipids Proteins Vitamins Minerals Nutrients consist of building blocks known as nutritional components: Carbohydrates are composed of monosaccharides, Lipids are made of fatty acids, Proteins are made of amino acids. 28 Basic Nutritional Components Generally, daily energy intake consists of: 55-60% from carbohydrates (CH), 25-30% from fats, 10-15% from proteins. At least 20% of energy should come from carbohydrates. If this requirement is not met, metabolic acidosis may develop. 29 After digestion, the basic building blocks absorbed from nutrients are: ❖ Glucose ❖ Fruktose ❖ Galactose ❖ Amino acids ❖ Fatty acids ❖ Glycerol 30 Specific Dynamic Effect Energy is expended during the digestion and absorption of nutrients, which is known as the specific dynamic effect. About 30% of the energy from proteins, 6% from carbohydrates, 4% from fats is consumed during digestion and absorption.  In nutrition, the main source of energy is carbohydrates, and the only source of 31 nitrogen is proteins. Energy Deficiency and its Effects When the energy provided by food is less than the body's requirements, the following occur in order: Fat stores deplete (weight loss), Serum protein synthesis decreases, leading to hypoalbuminemia as the first sign. In more advanced stages, muscle proteins break down, resulting in a negative nitrogen balance, Metabolic changes (e.g., ketoacidosis, cation loss, dehydration) occur, Susceptibility to infections increases. 32  Energy Production and ATP in Living Organisms Energy can be used in various forms, such as mechanical, chemical, electrical, heat, and light, and can be converted from one form to another. However, living cells cannot use heat as a source of energy. For vital life processes (such as respiration, blood flow, ion transport, and maintaining the optimal temperature), chemical energy is utilized. The necessary chemical energy is obtained from the breakdown of the building blocks that make up nutrients.33  Energy production through the oxidation of nutrients occurs in three stages: 1. Large molecules from food are broken down into smaller molecules (e.g., proteins into amino acids). These processes, which are primarily preparatory, do not release usable energy. 2. Most of the glucose, glycerol, fatty acids, and amino acids are converted into a simpler molecule, the acetyl group of acetyl coenzyme A (acetyl-CoA). A small amount of ATP is produced at this stage. 3. The acetyl group of acetyl-CoA undergoes complete oxidation. This occurs through the tricarboxylic acid (TCA) cycle, which is the final common pathway of oxidation for fuel molecules. During the oxidation steps in the TCA cycle, electrons are transferred to compounds like NAD+ and FAD, which can accept and donate electrons. These electrons are transferred to oxygen (O2) through the electron transport chain (ETC), leading to the production of significant amounts of ATP. 26 Energy Energy is defined as the capacity of a system to do work. Some biomolecules have high chemical potential. When these molecules undergo reactions or hydrolysis to products with lower potential, the difference in chemical potential between the reactants and products is called Gibbs free energy change (ΔG). 35 For a reaction to occur spontaneously, the difference in chemical potential between the products (P2) and the substrates (P1) must be negative. P2 < P1 so G negative, and the reaction proceeds spontaneously. Such reactions are called exergonic reactions. Reactions with a positive ΔG cannot proceed spontaneously and require energy input. These are called endergonic reactions. 31 In living cells, exergonic reactions result in the synthesis and storage of adenosine triphosphate (ATP). The energy released from the oxidation or breakdown of biomolecules is partly lost as heat, while the rest is converted into chemical energy and stored as ATP. 37 ATP (Adenosine Triphosphate) ❖ A nucleotide (adenine-ribose-triphosphate) 38 For every mole of ATP hydrolyzed, -73 kcal of energy is released The three phosphate groups are linked by high- energy phosphate bonds (acid anhydride bonds). The first phosphate group is attached to ribose via a phosphodiester bond. During hydrolysis of these bonds, free energy change (ΔG) is negative, making ATP hydrolysis a strongly exergonic reaction. The synthesis of ATP from ADP, however, is a strongly endergonic reaction. 39 Biochemical reactions typically occur at around pH 7 and 36-37°C. The unit of energy is expressed in joules (J), but in nutrition and biochemistry, the term calories (cal) is often used instead. 1 cal = 4.184 J. The calorific content of carbohydrates, proteins, and fats differs. For example: The oxidation of 1 gram of fat provides 9 kcal, The oxidation of 1 gram of carbohydrate or protein provides approximately 4 kcal. 35 Uses of ATP in the Body: Biosynthetic reactions that require energy, Movement and muscle contraction (mechanical work), Maintaining body temperature, Pumping ions across cell membranes. 41 Molecules having more energy than ATP; ▪ Phosphoenolpyruvate ▪ 1,3-diphosphoglycerate ▪ Phosphocreatine Gibbs free energy released is ~10 kcal/mol. Molecules having less energy than ATP; Glucose-6-phosphate Glycerol-3-phosphate AMP Gibbs free energy released is ~4 kcal/mol. 42 The ranking of phosphate compounds from high-energy to low-energy; Phosphoenolpyruvate Carbamoyl phosphate 1,3bisphosphoglycerate Phosphocreatine ATP ADP Glucose-1-P Fructose-6-P AMP Glucose-6-P Glycerol-3-P 43 ATP: an intermediary phosphate-containing compound. ADP both receives phosphate from ATP and donates phosphate in a lower-energy form. Nucleotides synthesized from ATP are used in various biosyntheses. 40 Transport of biomolecules and ions across the cell membrane occurs via: Passive transport Active transport ✓ Passive transport mechanism: substances move through the concentration gradient using their kinetic energy. ✓ Facilitated passive diffusion: ions and polar molecules diffuse through channels or are transported by specific carrier proteins through the concentration gradient without using energy. 46 Active transport: Energy expenditure is required for movement against the concentration gradient. In active transport, if the hydrolysis of ATP occurs during the passage of the transported substance through the membrane, it is called PRIMARY active transport. In some cases, a molecule moves into the cell coupled with another substance (e.g., Na ion) moving down its concentration gradient. To maintain this, the Na ion must be transported back outside the cell using ATP hydrolysis, a process known as secondary active transport. 47 Secondary Active Transport: Requires ⚫ energy. ⚫ specific carrier protein ⚫ Na ions. Glucose and galactose are taken into the intestinal cell via Na-dependent active transport. As Na moves down its concentration gradient into the cell, glucose (or galactose) is also carried along against its concentration gradient. When Na concentration inside the cell increases, it is pumped out by Na-K ATPase. The energy required for this process is provided by 48 ATP (secondary active transport). (a) Passive diffusion (b) Facilitated passive diffusion (c) Active transport 44 50 ATP synthesis mechanisms: 1. Substrate-level phosphorylation 2. Oxidative phosphorylation 51 1. Substrate-level phosphorylation 52 53 2. Oxidative Phosphorylation Electron Transport Chain (ETC) Glucose, fatty acids, and amino acids undergo a series of metabolic processes until they are broken down into CO₂ and H₂O. During the formation of intermediate products, coenzymes like NAD and FAD donate electrons to form energy-rich NADH and FADH₂. These reduced coenzymes (NADH and FADH₂) are specialized electron carriers. As electrons pass through the ETC, they lose free energy. Some of this energy is captured and used to synthesize ATP from ADP and Pi, producing high-energy compounds and storing energy. This process is called oxidative phosphorylation. 53 56 Oxidative phosphorylation: Occurs only in the presence of oxygen and in the mitochondria. In the mitochondria, the electrons carried by reduced coenzymes (NADH+H⁺ and FADH₂) are transferred to oxygen, producing ATP and H₂O. This electron transfer is an oxidation-reduction (redox) reaction. 57 https://prezi.com/fp1xbns8gtv6/mitokondri/ 58 Mitochondria Mitochondria, one of the cell organelles, is the energy production center. They are surrounded by a double membrane. The inner membrane is rich in proteins and participates in ETZ and oxidative phosphorylation. There are special pores in the outer membrane of the mitochondria. These allow the passage of small molecules and ions. The inner membrane is impermeable to many small ions (H+, Na+, K+) and molecules (ATP, ADP, pyruvate) and other metabolites important in mitochondrial function. 59 Electrons are released in oxidation reactions and are captured by NAD⁺ or FAD coenzymes. These coenzymes are reduced and take the role of electron donors. Electrons are then transferred step-by-step through the ETC in the inner mitochondrial membrane until they are accepted by oxygen. The oxygen then combines with electrons and protons to form water. Number of ATP synthesized; For 1 mol NADH+H+ … … … … ….. 2,5 ATP For 1 mol FADH2 ………… 1,5 ATP 60 There are five enzyme complexes in the inner mitochondrial membrane. These are designated as Complex I, II, III, IV, and V. Complexes I-IV form the electron transport chain, while Complex V catalyzes ATP synthesis (ATP synthase). Complex I: NADH dehydrogenase Complex II: Succinate dehydrogenase Complex III: Ubiquinol-cytochrome c oxidoreductase Complex IV: Cytochrome oxidase Complex V: ATP synthase (mitochondrial ATPase or F1F0 ATPase) 63 The process in which electrons carried by NADH or FADH₂ reach oxygen is called electron transport. During this transport, the energy released is used to phosphorylate ADP into ATP, a process called oxidative phosphorylation. The proteins involved in electron transport contain elements that can easily bind and release electrons Electron-carrying groups in ETZ; ⚫ Flavins ⚫ Iron-sulfur (Fe-S) clusters ⚫ Heme group 64 ⚫ Copper (Cu) ions The most important among these is iron, which can switch between two different ionic charges (Fe²⁺ and Fe³⁺). Iron is found in the structure of electron carrier proteins as an Fe-S group or bound to the heme group. The heme group is found in proteins known as cytochromes, which act as electron carriers. There are three classes of cytochromes (cytochrome a, b, c), and the Fe in the heme undergoes Fe²⁺ to Fe³⁺ transformations to facilitate electron transport. Copper (Cu) ions in these electron carrier proteins also undergo Cu²⁺ to Cu⁺ transformations to transport electrons. 65 One of the members of ETZ, co-enzyme Q; is a quinone derivative with a long isoprenoid tail, also called ubiquinone. It is the only member of the chain that is not protein-structured. 66 Control of oxidative phosphorylation The occurrence of oxidative phosphorylation depends on the availability of NADH, O2, ADP and Pi sources. The most important factor determining the rate is ADP levels. The regulation of the rate of oxidative phosphorylation by ADP concentration is called “respiratory control”. 67 Genetic Defects in Oxidative Phosphorylation Of the 100 polypeptides required for Oxidative Phosphorylation, 13 are encoded by mitochondrial DNA (mtDNA). Errors in oxidative phosphorylation usually result from changes in mtDNA. Organs that require more ATP, are more affected by errors in Oxidative Phosphorylation. Examples of diseases: ⚫ Leber’s hereditary optic neuropathy ⚫ Myoclonic epilepsy and red fiber disease ⚫ (MERRF)Hereditary paraganglioma 80