Biochemistry Overview PDF 2024/2025
Document Details
Uploaded by EasierMiracle
University of Tanta
2024
محمود سيف النصر عبد الهادي السيد
Tags
Summary
This document is a biochemistry overview for first-year nursing students. It covers topics such as oxidative stress, antioxidants, and the effects of free radicals. The content includes an explanation of the different types of reactive oxygen species.
Full Transcript
ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2024/2025 1 2024/2025 2024/2025 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ For 1st year Nursing Students...
ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2024/2025 1 2024/2025 2024/2025 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ For 1st year Nursing Students Table of Contents Chapter Page Biochemistry Overview. 3 Chapter 1: - Oxidative Stress 6 Chapter 2: - Minerals 14 2024/2025 2024/2025 2024/2025 Chapter 3: - Vitamins 25 Chapter 4: Carbohydrate chemistry 43 Chapter 5: Lipid chemistry 53 Chapter 6: Amino acids chemistry 64 Chapter 7: Enzymes 68 Portfolio Project 2 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Biochemistry Overview 2024/2025 2024/2025 2024/2025 3 Biochemistry Overview Origin of Chemistry: The term "chemistry" is derived from the Greek word chemi, meaning "the black land," a reference to ancient Egypt. Even in ancient Indian medical science, the metabolic and genetic foundations of diseases were understood. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Aim of Biochemistry: Biochemistry serves as the language of biology and a vital tool for research across all branches of medicine. Understanding biochemistry is essential to grasp the basic functions of the human body, such as: Cellular Functions: Exploring how food is digested, absorbed, and utilized at the molecular level to maintain bodily processes. Energy Production: Examining how the body generates energy for daily activities. Metabolic Interconnections: Understanding how different metabolic pathways are linked. Genetic Functions: Investigating the role of genes in controlling biological processes. Immune Resistance: Uncovering the molecular basis for the body's defense against pathogens. Biomolecules: 2024/2025 2024/2025 2024/2025 More than 99% of the human body consists of six key elements: oxygen, carbon, hydrogen, nitrogen, calcium, and phosphorus. The body is composed of: 60% Water 15% Proteins 15% Lipids 2% Carbohydrates 8% Minerals These biomolecules originate from 30 essential precursors, often called the "alphabet of biochemistry," which include: 20 Amino Acids 2 Purines and 3 Pyrimidines Sugars like glucose and ribose Lipids such as palmitate and glycerol Choline 4 Molecular Complexity in Organisms: Biomolecules are organized in a hierarchy, progressing from small molecules to larger macromolecules: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 1. Monomers to Macromolecules: For example, glucose forms glycogen, and amino acids form proteins. 2. Macromolecular Complexes: Larger molecules like proteins, polysaccharides, lipids, and nucleic acids form complex structures within cells. 3. Supramolecular Systems: These macromolecules associate through non-covalent bonds to create functional units such as ribosomes and lipoproteins. This hierarchy of complexity is critical for understanding the structure and function of living organisms at the molecular level. 2024/2025 2024/2025 2024/2025 5 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Chapter 1 Oxidative Stress 2024/2025 2024/2025 2024/2025 Understand the concept of Oxidative stress Describe the meaning of Antioxidants Identify the different types Reactive oxygen species Demonstrate the dangerous effects free radicals Classify antioxidants 6 Chapter 1 Oxidative stress ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ *Free radical: - It is an atom or a molecule that has one or more (unpaired) electron. - It is unstable & highly reactive because it tends to acquire an electron from other substances *Pro-oxidant: - They are substances that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidants system. *Antioxidant: - It is a molecule stable enough to denote an electron to a free radical to neutralize it, thus reducing its capacity to damage 2024/2025 2024/2025 2024/2025 7 * Oxidative stress: Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2024/2025 2024/2025 2024/2025 I-Reactive oxygen species (ROS) & Reactive nitrogen species (RNS): - Reactive oxygen species (ROS) Are reactive chemical species containing oxygen. They include superoxide (O2 ), hydroxyl (OH ) , peroxyl (RO2 ), alkoxyl (RO ) radicals, hydrogen peroxide H2O2 and singlet oxygen (O2). - Reactive nitrogen species (RNS) Is a collective term that includes Nitric oxide radical (NO ), nitrogen dioxide radical (NO2 ), peroxynitrite (ONOO −) and other oxides of nitrogen and products arising when NO reacts with O2 and other free radicals. 8 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ II- Sources of free radicals: a- Internally generated sources: 1-2024/2025 Mitochondria. 2024/2025 2024/2025 2- Peroxisomes 3- Phagocytes. 4- Xanthine oxidase. 5- Arachidonate pathways (cyclo- and lipoxygenase). 6- Reactions involoving iron and other transitions metals. 7- Inflammation. 8- Ischemia/reperfusion injury. b- Externally generated sources: 1- Ultraviolet rays & radiation. 2- Environmental pollution. 3- Cigarette smoking. 4- Drugs & industrial solvents 9 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ III- Dangerous effects of free radicals: a- Proteins: 1- Oxidation of proteins by ROS/RNS can generate a range of reactive products such as protein hydroperoxides that can generate additional radicals particularly upon interaction with transition metal ions. 2024/2025 2024/2025 2024/2025 b- Carbohydrates: 1- Free radicals such as OH react with carbohydrates by randomly abstracting a hydrogen atom from one of the carbon atoms, producing a carbon-centered radical. c- Lipids: 1- Membrane lipids are highly susceptible to free radical damage. 2- During lipid peroxidation a large number of toxic products are also formed that can have effects at sites away from the area of generation, behaving as „second messengers‟. d- DNA: 1- Oxidative damage to DNA is a result of interaction of DNA with ROS or RNS. 2- Free radicals such as OH react with DNA by addition to bases or abstractions of hydrogen atoms from the sugar moiety >>>> mutations & carcinogenesis 10 *Classifications of antioxidant: The antioxidant defense system consists of I- Enzymatic antioxidants: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ a- Superoxide dismutase: 1- Superoxide dismutase (SOD) is an enzyme that dismutates superoxide radicals to form hydrogen peroxide (H2O2) and oxygen (O2). 2- It is considered to be the first line of defense against free radical formation. 3- Three isoforms of Super oxide dismutase (SOD1, SOD2, SOD3) are present in the mammalian cells. b- 2024/2025 Catalase: 2024/2025 2024/2025 1- Catalase is a common enzyme found in nearly all living organisms. It catalyzes the decomposition of hydrogen peroxide to water and oxygen. 2- It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS). 3- It has one of the highest turnover numbers of all enzymes; one catalase molecule can convert approximately 5 million molecules of hydrogen peroxide to water and oxygen each minutes 11 c- Glutathione peroxidase & Glutathione reductase: Glutathione peroxidase is an enzyme that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Glutathione reductase is a crucial enzyme that reduces glutathione disulfide (GSSG) to the sulfhydryl form (GSH) by the NADPH-dependent mechanism, an important cellular antioxidant system. 2024/2025 2024/2025 2024/2025 The order which the antioxidant system work is done through three steps as follows: First SOD, then Catalse and glutathione system works. 12 II- Non enzymatic antioxidants: A-Vitamins: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ The principal antioxidants vitamins include: vitamins E, Vitamin C and β-carotene B- Hormones: 1- Melatonin is involved in the synchronization of the circadian rhythms of physiological functions including sleep timing, blood pressure regulation, reproduction, and many others 2- It is also known to protect against radiation-induced cellular damage, as melatonin & its metabolites protect from oxidative stress by scavenging reactive oxygen species C- Minerals: - Selenium - Manganese. 2024/2025 2024/2025 2024/2025 - Copper - Zinc. D- Plant antioxidants: - Green tea/black tea. - Soya beans - Nigella sativa - Olives. 13 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Chapter 2 Minerals 2024/2025 2024/2025 2024/2025 By the end of the chapter student will be able - Identify minerals importance - Classify macro and micro minerals - Demonstrate causes and manifestations of mineral deficiency 14 Minerals *Definition: - They are inorganic compounds that are needed as structural components and regulators of body processes. *Classification: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ A-Macrominerals (Bulk elements): 1.They are required in amounts greater than 100 mg/day. 2. They include 7 elements: Calcium, phosphorus, sodium, potassium, chloride, sulfur, and magnesium. B-Microminerals (Trace elements): 1. They are required in amounts less than 100mg/day. 2. They include 11 elements: Iron, iodine, copper, zinc, fluoride, manganese, molybdenum, selenium, chromium, cobalt and silicon. 2024/2025 2024/2025 2024/2025 A-Macrominerals 1-Calcium I- Sources: 1- Milk and milk products are considered as the richest sources. 2- Leafy vegetables and egg yolk. II- Daily requirements: Child: 1000 mg/d Adults: 800 mg/d Pregnant women: 1500 mg/d III- Absorption: 1- Site: upper part of small intestine. 2- Absorption of calcium is active process and requires calcium binding protein present in the intestinal mucosal cells. 15 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ IV- Distribution of body calcium: Calcium is the most abundant mineral in the body (about 1200 grams). -99% of calcium: is present in bones and teeth. - 1 % of calcium: is present in body fluids and other tissues. 2024/2025 2024/2025 2024/2025 V- Plasma calcium: 1- Plasma calcium level ranges from: 9 - 11 mg / dl. 2- Forms: Plasma calcium is present in 2 forms: a- Diffusible Calcium: It forms 50% of total serum calcium & is present in ionized form (essential for blood clotting). b- Nondiffusible Calcium: Is present in combination with albumin & Can`t cross the cell membrane. VI- Factors affecting calcium level in the blood: A-Hormonal regulation: Three hormones are concerned with regulation of blood calcium, they are parathyroid hormone, active vitamin D (calcitriol) and calcitonin as they regulate calcium homeostasis: l- Parathyroid hormone (PTH): It increases plasma calcium level through: 16 1- Bone: Mobilization of calcium from bones (bone resorption). 2- Intestine: increases absorption of calcium from intestine (through conversion of vitamin D into calcitriol “active vitamin D” in the kidney). 3- Kidney: increases reabsorption of calcium by renal tubules (decreases calcium excretion) ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- Active vitamin D (Calcitriol or 1,25 dihydroxycholecalciferol): It increases blood calcium level through: 1- Bone: Mobilization of calcium from bones (bone resorption). 2- Intestine: increases absorption of calcium from intestine. 3- Kidney: increases reabsorption of calcium by renal tubules. 3- Calcitonin ( calcium lowering hormone) 1- It is a hormone that is secreted by the parafollicular or “C” cells of the thyroid gland & is released in response to hypercalcaemia and causes decrease of blood calcium level through - Bone: a- Inhibition of calcium mobilization from bones, b- Increasing calcium deposition in bones. - Kidney: 2024/2025 2024/2025 2024/2025 -Inhibits renal tubular cell reabsorption of Ca2+ allowing it to be excreted in the urine. B-Non hormonal regulation: 1- Solubility product: - Normally Ca/P ratio must be constant. - Ca x P in children is 50 and in adults are 40. If plasma phosphate increases (as in renal failure) the plasma, calcium decreases to keep the ratio constant. 2- Blood pH: -Ionization of calcium occurs at normal blood pH, 7.4.The more the acidosis of the blood pH, the more formation of ionized calcium. VII- Functions of calcium: 1 - Calcification of bones and teeth. 2- Regulation of transmission of nerve impulses 3-Regulation of contraction of muscles 4- Blood clotting mechanism. 17 5- Cardiac conduction. 6- Calcium acts as a second messenger for hormonal action. VIII- Hypercalcemia & Hypocalcemia: A-Hypercalcemia caused by: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 1- Primary hyperparathyroidism: usually due to adenoma (benign tumor). 2- Ectopic cells as in some malignancy increasing PTH 3- Excess intake of vitamin D: or calcium or both. 4- Bone diseases: (bone resorption) As in malignancy, leukemia, multiple myeloma 5- Effects: Stone formation: e.g renal stones & Calcification in different tissues. B- Hypocalcemia caused by: l- Hypoparathyroidism. 2- Alkalosis. 2024/2025 2024/2025 2024/2025 3- Kidney diseases where activation of vitamin D is inhibited. 4- Effects: a- Acute deficiency: tetany results with carpopedal spasm. b- Chronic deficiency: In children, Rickets and in adults, Osteomalcia. IX- Excretion of calcium: 1- Most of calcium excretion is eliminated with feces. 2- Small amount of calcium is excreted in urine (about 200 mg/day). 2- Phosphorous I- Source: 1- Milk and milk products. 2- Fish, meat, liver and kidney and Leafy vegetables and egg yolk. Phosphoprotein of diet such as casein of milk and vetillin of eggs. 18 II- Daily requirements: - Adults: 800-1000mg/d - Pregnant women: 1500- 2000mg/d III- Absorption: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 1- Phosphorus (in the form of phosphate) is absorbed by an active transport mechanism 2- Factors affecting absorption of calcium will affect the absorption of phosphorus as well. IV- Distribution in the body: -Total body phosphorus is about 700 gm, most of them (600 gm) is present in the skeleton (bones and teeth). V- Plasma phosphorous: 1- Normal plasma inorganic phosphorus: 3-5 mg/dl. 2- Other forms are present (organic phosphate): a- Nucleoproteins of all cells. b- Nucleotides. 2024/2025 2024/2025 2024/2025 c- Phosphoproteins & phospholipids. VI- Factors affecting phosphorous level in the blood: 1- Parathyroid hormone (PHT): - PTH decreases blood phosphorus by stimulating its excretion (through inhibiting its renal tubular reabsorption). 2- Active vitamin D ―Calcitriol‖: 1- Hypophosphatemia stimulates directly the renal hydroxylation of 25 into 1,25 dihydroxycholicalciferol (calcitriol). 2- Calcitriol increases blood phosphorus through stimulation of: a- Bone resorption i.e. mobilization of phosphorus from bones. b- Intestine: Absorption of phosphorus from the intestine. c -Kidney: Renal reabsorption by renal tubules VII- Function of phosphorous: It enters, in the structure of the following compounds: 1- Formation of bones: 19 Bone consists of protein which has been strengthened by deposition of calcium hydroxyapatite which is a calcium salt composed of calcium hydroxide and calcium phosphate 2- Plasma buffers (phosphate buffers). 3- Cellular components: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ a -Nucleic acids: DNA, RNAs. b- Phospholipids: e.g. lecithin, cephalin. c- Phosphoproteins: e.g.: casein of milk. d- Coenzymes: e.g. NAD, NADP. e- Second messengers: Cyclic AMP and cyclic GMP. f- High energy phosphate compounds e.g. ATP, GTP, creatine and phosphate. VIII- Excretion: Mostly (90%) is excreted in urine. 3- Sodium 2024/2025 2024/2025 2024/2025 I- Sources: -The main source of sodium is sodium chloride (Na Cl) which is added to food as common salt, it is also it is present in milk, cheese, eggs and vegetables. II- Daily requirements: - 5 gm/d of common salt are recommended for adults (this dose should be restricted in patients with hypertension). III- Absorption: -It occurs in small intestine (ileum). It is nearly completely absorbed. IV- Distribution: 1-2/3 of sodium is present in tissues & body fluids (the main extracellular cation) 2-About 1/3 of sodium is present in skeleton. V- Factors affecting plasma sodium: 1- Aldosterone and the rennin angiotensin system (increase Plasma sodium). 2-Changes in glomerular filtrate and renal blood flow. 20 3-Atrial natriuretic peptide: It is involved in control of body water, sodium, potassium and fat. VI- Functions: 1- Maintenance of osmotic pressure and volume of plasma and extracellular fluid. 2- Regulation of acid base balance. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 3- Transmission of nerve impulses & contraction of muscles. 4- Sodium acts as substrate for Na+/K+ ATPase enzyme (sodium potassium pump). VII- Excretion: - Sodium is excreted as sodium chloride in urine. - About 15 grams are excreted daily. Also it is present in body secretions (Saliva – Sweat) 4- Potassium I- Sources: - Meat, liver, orange, banana and other fruits and vegetables are rich sources of potassium. II- Requirements: 2024/2025 2024/2025 - Children: 1-3 gm/d - Adults: 2-4 gm/d2024/2025 III- Absorption: - Rapidly occurs in the small intestine. IV- Distribution: 1- 2/3 of potassium is present in tissues and body fluids (K + is the main intracellular cation). 2- About 1/3 is present in skeleton. V- Plasma potassium:Plasma potassium: 3.5-5 mrnol/L. VI- Functions: 1- Maintenance of osmotic pressure and volume of plasma and intracellular fluid. 2- Regulation of acid base balance. 3- Transmission of nerve impulses & contraction of muscles. 4- Sodium acts as substrate for Na+/K+ ATPase enzyme (sodium potassium pump) VII- Excretion: - Mainly through urine. 21 Trace Elements 1-Iron I- Sources: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ - Meat, liver, kidney, some plant sources ( nuts, beans, dates) are good sources of iron. II- Requirements: - Adults: 10 mg/day. - Pregnant and lactating women: 30 mg/day. III- Absorption & Transport: 1- Absorption of iron occurs in the duodenum and the proximal part of the jejunum. 2- Iron is absorbed in ferrous status 3- Inside the intestinal cells, it is oxidized to ferric state (Fe+3) and combines with apoferritin in order to form ferritin (the main storage form of iron in cells). 2024/2025 2024/2025 2024/2025 4. Later, ferritin releases ferrous iron into the capillaries according to the body needs. * Factors affecting absorption: 22 IV- Distribution of iron: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ V- Plasma iron: -The total body iron of an adult male is 3-5 grams. VI- Functions: 1- Hemoglobin: which carries oxygen. 2- Myoglobin: which stores oxygen. 2024/2025 2024/2025 2024/2025 3- Respiratory enzymes: which use oxygen. 4- Cytochrome P450: which detoxicates drugs and oxygen. 5- Other enzymes: catalase, peroxidase and tryptophan oxygenase. VII- Clinical abnormalities: A-Iron deficiency anemia:Causes: Decreased intake e.g. malnutrition. Decreased absorption e.g. achlorhydra (absence of HCl). Increased loss as in hemorrhage, delivery and in heavy menstruation. Increased requirements as in pregnancy & lactation. Heavy infestation by parasitic worms (helminths) such as tapeworms, flukes, and roundworms. 23 VIII- Excretion: -Urine contains only trace amounts of iron -The iron of the broken blood cells is stored or used again in the formation of hemoglobin of new red blood cells. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2-Iodine I- Sources: 1- lodinized table salt will provide daily body needs. 2- Fish, seafood and vegetables. II- Requirements: For adult: 100 - 150 ug/day. III- Absorption: Small intestine is the main site of absorption. IV- Blood iodine: 2024/2025 2024/2025 2024/2025 The level of protein bound iodine 4-8 mg/100 ml of blood,it is the circulating thyroid hormone. IV-Functions: -Iodine is needed for the formation of thyroid hormones (T3 - T4). VII- Excretion: -Mainly (70%) in urine. 24 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ CHAPTER 3 Vitamins 2024/2025 2024/2025 2024/2025 25 VITAMINS They are organic compounds that are needed in small amounts in the diet. - They differ from other organic compounds in that: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ a-Theydo not enter into tissue structure. b-Theyare not used in the body for energy production as carbohydrates, fats & proteins. * Pro-vitamins: Are substances that are converted in the bodyinto vitamins e.g.: β carotenes are provitamin A. * Vitamers: Are structural analogs of the vitamins. Typically not all vitamers have exactly the same vitamin potency. II- Classification: According to their solubility, vitamins can be classified into two major groups: 2024/2025 2024/2025 2024/2025 26 Fat Soluble Vitamins Vitamin A Anti-night blindness vitamin ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ I- Structure& Forms: 1- Vitamin A is derived from carotenes i.e. carotenes are provitamin A. 2- Carotenes are pigments made byplants and cannot be made by animals. Carotenes are responsible for the orange colour of carrots and manyother fruits & vegetables. 3- There are three forms of vitamin A: 1- Retinol. 2- Retinal. 3- Retinoic acid. II- Sources: 1- Plants source: All pigmented vegetables and fruits as potatoes, carrots, tomatoes and leafy green vegetables. 2- Animals source: Liver, milk, fish, butter, eggs and Cod liver. 2024/2025 2024/2025 2024/2025 III- Requirements: *Recommended daily allowance (RDA): - Children: 300 ug/d. - Adult: 600 ug/d - Pregnancy: 770 ug/d. IV- Functions of vitamin A: 1- Vitamin A & Vision: a- The retina of the eye has two types of cells: rods and cones. b- The rods are in the periphery & responsible for dim light vision while cones are at the center of retina & are responsible for day vision. c- Rhodopsin is a conjugated protein present in rods, it contains 11-cis-retinal & the protein opsin (2 forms of vitamin A). d- When light falls on retina, 11-cis-retinal is isomerized to all-trans-retinal. 2- Vitamin A is essential for healthy epithelial tissue. 3- Vitamin A is involved in cell growth & differentiation and proper immune system. 4- Important in bone & teeth formation. 5- Essential for reproduction. 6- Present in high concentration of adrenal cortex. 27 V- Deficiency: 1- Night blindness (The inability to see in dim light): a- First night vision is influenced and dayvision is less influenced. b- Regeneration of active rhodopsin requires opsin and 11-cis-retinal. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- Xerophthalmia (Dry eye): -Pathologic dryness of the conjunctiva and cornea. The conjunctiva becomes dry, thick and wrinkled. If untreated it leads to corneal ulceration and blindness as a result of corneal damage. 3- Keratomalacia: If xerophthalmia persists for a long time, it progress to keratomalacia i.e. softening of cornea & degeneration of corneal epithelium which gets vascularized. Later, corneal opacities develop bacterial infections leading to corneal ulceration, perforation of cornea &blindness. 4- Effect on skin and epithelial cells: -The skin becomes rough and dry. -Keratinization of epithelial cells of GIT, urinary tract and respiratory tract with increased incidence of secondary bacterial infection. - Degeneration 2024/2025 of germinal epithelium leads 2024/2025 to sterility in male 2024/2025 Vitamin D I- Structure & forms: 1- Vitamin D is a sterol, it contains steroid nucleus. 2- Vitamin D functions like a hormone. 3- It occurs in two forms: - Vitamin D2 (Ergocalciferol). - Vitamin D3 (Cholecalciferol). 4- They are derived from certain precursors (Pro-vitamins) on exposure to sunlight: - Ergosterol: is the precursor of vitamin D2 (Ergocalciferol) & of plant origin. - 7 Dehydrocholesterol: is the precursor of vitamin D3 (Cholecalciferol) & of animal origin. 5- The production of vitamin D in the skin is directly proportional to the exposure to sunlight. NB:-Vitamin D3 (Cholecalciferol) is not the active form of vitamin D, it is hydroxylated (at position 25) in the liver to form 25 hydroxycholecalcifrol by hydroxylase. 28 -This compound is further hydroxylated (at position 1) in the kidney to form the metabolically active form of the vitamin 1,25 dihydroxycholecalciferol (calcitriol) by 25- hydroxycholecalciferol 1- hydroxylase. II- Sources: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ -Vitamin D2: mushrooms are excellent source. -Vitamin D3: Fish liver oils such as cod liver oil, Fattyfish species such as: Salmon, Mackerel, Tuna, Sardines, canned in oil & Cooked egg yolk. III- Requirements: - children 400 IU/day - Adults up to 600 IU -Pregnant is 700 IU. IV-Functions & Effects: -The overall function of 1,25 dihydroxycholicalciferol is to maintain adequate plasma levels of calcium. Generallyit performs this function by acting on the following organs: 1-Effect of vitamin D on the intestine: - It increases the intestinal absorption of calcium and phosphorous. 2-Effect 2024/2025of vitamin D on bone: 2024/2025 2024/2025 - In osteoblasts of bone, calcitriol stimulates calcium uptake for deposition as calcium phosphate 3-Effect of vitamin D on kidney: - It is also involved in minimizing the excretion of calcium and phosphate through the kidney by decreasing their excretion and enhancing reabsorption. V- Deficiency: -Vitamin D deficiency causes rickets in children and osteomalacia in adults. A-Rickets Rickets in children is characterized bybone deformities due to incomplete bone mineralization. -Nutritional ―classical‖ rickets: a- It results from inadequate sunlight exposure or inadequate intake of dietary vitamin D, calcium, or phosphorus. Nutritional rickets presents in the first two years of life with b- Developmental delay: delayed dentations, sitting, and walking and teeth formation. c-Characteristic findings: Diminished mineralization of bone results in softening and deformities of bone: bow legs, knock knees, pigeon chest, Kyphosis, Lordosis, softening of skull. 29 d- Short stature, gait abnormality. Biochemical findings: 1- Decreased serum calcium (NV: 9-11mg/dl) ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- Decreased plasma phosphorous (NV: 3-4.5 mg/dl) 3- Increased plasma alkaline phosphatase (NV: 30-130 IU) B-Osteomalacia: 1- Osteomalacia is the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. 2- The most common cause of osteomalacia is a deficiency of vitamin D, which is normally derived from sunlight exposure and, to a lesser extent, from the diet. 3- Homebound elderly populations are at particular risk for vitamin D deficiency, as these populations receive little sun exposure. 4- In addition, both the efficiencyof vitamin D synthesis in the skin and the absorption of 2024/2025 2024/2025 2024/2025 vitamin D from the intestine decline with age. Vitamin E I- Structure & forms: 1-Vitamin E exists in eight isoforms which are α, β, γ and δ tocopherols and α, β, γ and δ tocotrienols (α –Tocopherol is most active and predominant form of vitamin E). II- Sources: 1- Plant source: Wheat germ oil, Sunflower oil, Almond oil, Palm oil & Olive oil. 2- Animal sources: "Poor sources" e.g. liver, egg yolk and meat III- Requirements: - Children 10 mg/day - Adult 15 mg/day - Pregnancy & lactation 20 mg/day 30 IV- Functions: 1- Antioxidant function: a- Most of the functions of the vitamin E are related to its antioxidant property. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ b- As an antioxidant, vitamin E acts as a peroxyl radical scavenger, disabling the production of damaging free radicals in tissues, by reacting with them to form a tocopheryl radical *It protects the polyunsaturated fatty acids (PUFA) from peroxidation reactions: a- It is essential for membrane structure and integrity, hence it is membrane antioxidant. b- It prevents the peroxidation of PUFA. c- It protects the RBC from hemolysis byoxidizing agents (H2O2). 2-Vitamin E also plays a role in neurological functions & inhibition of platelet coagulation. V- Vitamin E deficiency: 1- Anemia-due to oxidative damage to red blood cells. 2- 2024/2025 Neuromuscular problems-such as ataxia, peripheral 2024/2025 neuropathy and myopathies. 2024/2025 3- There is also some laboratory evidence that vitamin E deficiency can cause male infertility. Vitamin K I- Structure & forms: - Vitamin K members are naphthoquinone derivatives. They differ in the nature of the side chain. 1- Vitamin - K1: Phylloquinone. 2- Vitamin - K2: Menaquinone 3- Vitamin - K3: Menadione. II- Sources: 1- Vitamin K1: Present in plants as Spinach, broccoli and cabbage. 2- Vitamin K2: Produced by the intestinal bacteria. 3- Vitamin K3: It is a synthetic form of vitamin K. III-Requirements: Children: 60 mcg/day Adults: 75 mcg/day Pregnant female : 120 mcg/day 31 IV- Functions: 1-The functions of vitamin K are concerned with blood clotting process: 1-Vitamin K is required in the hepatic synthesis of prothrombin and blood clotting factors II, VII, IX, and X. These proteins are synthesized as inactive precursor molecules. Formation of the ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ clotting factors requires the vitamin K-dependent carboxylation of glutamic acid residues. NB: Vitamin K antagonists: -Dicumarol & Warfarin have structurally similarity to vitamin K & block the regeneration of active form of vitamin K V- Deficiency: 1- Inadequate absorption of the vitamin byintestine as in absence of adequate amount of bile salts as in obstructive jaundice and bile fistula. 2- Deficiency in newborn infants: -Sterile intestinal flora & little vitamin K crossing the placental barrier from maternal circulation 3- Another at-risk group for deficiency: Those subject to broad spectrum antibiotic use as taking broad-spectrum antibiotics can reduce 2024/2025 2024/2025 2024/2025 vitamin K production in the gut compared with those not taking these antibiotics. N.B.: Dietarydeficiency is extremely rare unless the small bowel was heavily damaged, resulting in malabsorption of the molecule. - Clinical features of deficiency: Includes tendency to bleed for long time (Prolonged bleeding time) after slight injury or operations, due to inadequate formation of blood clotting factors Water soluble VitaminsVitamin C I- Structure & Forms: 1- Ascorbic acid which is a hexose derivative & closely resembles monosaccharides in structure. 2- Vitamin C exists in two forms: a- L-ascorbic acid (reduced form) 90%. b- b- L-dehydro-ascorbic acid (oxidized form) 10%. 32 *Properties: 1. Ascorbic acid is acidic because it contains two enol groups. 2. Vitamin C is the most labile vitamin in food i.e. easy to be destroyed (by heat). 3. It is oxidized by ascorbic acid oxidase into dehydro L-ascorbic acid. Further oxidation ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ forms oxalic acid and thereonic acid. II- Sources: 1- Plant source: citrus fruits melon, tomatoes and Vegetables: potatoes, and green peppers. 2- Animal source: Vitamin C is mostlypresent in the liver and least present in the muscle. III- Requirements: - RDA for adult: 75-90 mg per day. Pregnancy: 85-120 mg per day. IV- Functions: 1- 2024/2025 Collagen formation: 2024/2025 2024/2025 a- Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendons, ligaments and skin. It is also abundant in corneas, cartilage, bones, blood vessels, the gut, and the dentin in teeth. b- Vitamin C is required in the hydroxylation of proline & lysine into hydroxyproline & hydroxylysine respectively by hydroxylase enzyme (L-ascorbic acid is necessary for keeping its iron atom in ferrous state) hydroxyproline & hydroxylysine are involved in collagen synthesis. 2- Formation of norepinephrine: -Vitamin C is required for the formation of norephnephrine from dopamine as it is required for the action of dopamine monooxygenase (Thus adrenal medulla is rich in vitamin C). 3- Antioxidant action: - Acts as antioxidant & protects tissues from toxic effect of some oxidants that may cause cancer. 4- Vitamin C is concentrated in the lens of eye. 5-Absorption and mobilization of iron: Ascorbic acid is a potent reducing agent, keeping iron in ferrous state. 6- It enters in a reaction involving the reduction of folic acid to tetrahydrofolic acid. 33 V- Deficiency: Scurvy Hemorrhagic tendency: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ a- In ascorbic acid deficiency, collagen is abnormal & the intracellular cement substance is brittle, so capillaries are fragile, leading to the tendency to bleed even under minor pressure. b- Petechial hemorrhages: Due to rupture of capillaries. c- Internal bleeding: In severe cases, hemorrhage may occur in the conjunctiva & retina. d- In severe cases of scurvy, the gums become painful, swollen, spongy and bleeding occurs. e- Wound healing may be delayed. 2-Anemia (microcytic, hypochromic), a. Loss of blood by hemorrhage b.2024/2025 Decreased iron absorption 2024/2025 2024/2025 c. Decreased tetrahydrofolic acid d. Accumulation of met-hemoglobin (iron is ferric) Vitamin B complex Vitamin B1 (Thiamine) I- Structure: 1- Thiamine is a sulphur containing water soluble vitamin. 2- Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin. II- Sources: - Yeast (yeast extract) is the most highly concentrated sources of thiamine. III- Requirements: - Children is 0.5 mg/day.- Adults 1-mg/day. Pregnancy & lactation : 1.4 mg/day. 34 IV- Deficiency: Beriberi Beriberi has been common in regions where polished or white rice forms a major part of the diet, ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ which has its husk removed to extend its shelf life and palatability but has the side effect of removing the primary source of thiamine. *There are two main types if the disease: 1- Dry beriberi: - characterized bywasting and partial paralysis resulting from damaged peripheral nerves. - It is also referred to as endemic neuritis. It is characterized by: 1- Peripheral neuritis with loss of sensation (numbness) in hands and feet. 2- Loss of muscle function or paralysis of the lower legs. 3- Muscle weakness & walking becomes difficult. 2024/2025 2024/2025 2024/2025 4- Mental confusion & poor memory 5- Ataxic gait. 2- Wet beriberi: - Affects the heart and circulatory system, It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. - Wet beriberi is characterized by: 1. Increased heart rate. 2. Dyspnea (shortness of breath) on exertion. 3. Peripheral edema. 35 Vitamin B3 (Niacin-Nicotinic acid) I- Structure: 1- It is a derivative of pyridine ring ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- Nicotinamide is the amide form of nicotinic acid. 3- Active forms: Niacin is converted to the active form nicotinamide that enters in the structure of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). II- Requirements: -RDA in children: 12 mg/day. Adults: 14-16 mg/day. Pregnancy: 18 mg/day. III- Source: 1- Plant source: - Whole grain cereals richest source. 2- Animal source: - Liver, meat, kidney and chicken. 2024/2025 2024/2025 3- It is formed in the body as a metabolic product of amino acid tryptophan.2024/2025 (60 mg of tryptophan → 1 mg nicotinic acid) -Maize is deficient in both nicotinic acid and tryptophan and thus in farmers who depend on maize as the main diet pellagra is common. NB-Lowering plasma cholesterol: - Niacin strongly inhibits lipolysis in adipose tissue (which is the primary producer of circulating free fatty acids). - The liver normally uses these circulating fatty acids as a major precursor for triacylglycerol synthesis. - Thus, niacin causes a decrease in liver triacylglycerol synthesis, which is required for very-low- density lipoprotein production. 36 IV- Deficiency: Pellagra 1- Niacin deficiency, results in decreased NAD production leading to most of the pathology. 2- It tends to occur in areas where people eat maize (corn) as a staple food, since it is the only ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ grain low in digestible niacin. 3- Pellagra is a disease involving the skin, gastrointestinal tract and CNS. The symptoms of pellagra progress through the three Ds: dermatitis, diarrhea, dementia and, if untreated, death 4- Common psychiatric symptoms of niacin deficiency include irritability, poor concentration. 5- Other causes of Pellagre are: a- Hartnup's disease. b- Carcinoid syndrome. c- Vitamin B6 deficiency. d- Alcoholism e- Medications as anti-convulsant & Immunosuppressive drugs. 2024/2025 2024/2025 2024/2025 Vitamin B6 I- Structure: 1- Vitamin B6 refers to a group of very similar chemical compounds which can be interconverted in biological systems to each other they include: pyridoxine, pyridoxal and pyridoxamine. 2- The active form is pyridoxal 5′-phosphate (PLP) which serves as a coenzyme in many enzymatic reactions in amino acid, glucose and lipid metabolism. II- Requirements: - Children: 1.0 mg/day. Adults: 1.7 mg/day, - pregnancy: 2 mg/day. III- Sources: 1- Plant source: - Yeast, potatoes and germinal portion of various seeds. 2- Animal source: - Egg yolk, meet, turkey and liver. 37 IV- Deficiency causes: 1- The elderly and alcoholics have an increased risk of vitamin B6 deficiency, as well as other micronutrient deficiencies due to impaired absorption. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, and hydrocortisone negatively impact vitamin B6 status, hemodialysis reduces vitamin B6 levels. *Symptoms and signs: 1- Disturbance in amino acids absorption and metabolism leads to growth retardation and maylead to mental retardation as well. (Defect in protein synthesis and metabolism). 2- Neurological manifestations: a- PLP is involved in the synthesis of sphingolipids, so B6 deficiency leads to demyelination of nerves and consequent peripheral neuritis. b- Convulsions in young infants due to deficient formation of GABA which is an inhibitory 2024/2025 2024/2025 2024/2025 transmitter in brain. 3- Hematological manifestations: a- Sidroblastic anemia is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). Sideroblasts are atypical, abnormal nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in the mitochondria surrounding the nucleus. b- In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently, in vitamin B6 deficiency this occurs due to deficient heme formation which can`t bind to the globin part. 4- Pellagra: As vitamin B6 is required in the synthesis of niacin (the kynurinase enzyme step). 5- Homocysteinuria: It is due to inability to convert Methionine to cysteine. 38 Folic acid I- Structure: 1- Folic acid Consists of: a- Pteridine ring. b - Para-amino benzoic acid c- Glutamic acid. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2- The active from of the folic acid is tetrahydrofolic acid (THF). Folic acid must be reduced before it acts as a coenzyme. First to 7,8 dihydrofolic acid then to 5,6,7,8 tetrahydrofolic acid, catalyzed by reductase which use NADP as a hydrogen donor. II- Sources: 1- Plant source: Vegetables fruits, nuts, beans, peas, Avocado, beetroot, spinach and yeast. 2- Animal source: Dairyproducts, poultry, meat, eggs, liver, seafood and some grains. Requirements: III-2024/2025 2024/2025 2024/2025 children: 200 micrograms/day. adult: 400 micrograms/day. pregnant 600 micrograms/day. IV- Deficiency: *Dietary deficiency is the most common cause of folic acid. It is caused by: 1- Inadequate intake seen in alcoholics 2- Impaired absorption due to small intestinal diseases. *Signs & symptoms: 1- The manifestations are due to defective synthesis of DNA and RNA leads to defective cell formation & division including blood cells. 2- The manifestations of folate deficiencyinclude the following: a) Pancytopenia: i.e. all blood cells are affected. - Megaloblastic anemia: (macrocytic anemia). - Leucopenia: decreased W.B.Cs. - Thrombocytopenia: - decreased Platelets. 39 b) Impaired growth and in fetus: 1- Neural tube defect is one of the most common birth defects, Specific types include: spina bifida which affects the spine, anencephaly which results in little to no brain. 2- For the production and maintenance of new cells, for DNA synthesis and RNA synthesis. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Vitamin B12 I- Structure: 1- Corin ring 2- Cobalt atom at the center of the corin ring which is attached to a- Nucleotide side chain at one side b- Cyanide group at the other side. 3- Since vitamin B12 contains a cobalt atom and a cyanide group, it is called cyanocobalamine. 2024/2025 2024/2025 2024/2025 II- Sources: -Animals obtain the vitamin from their natural flora or by eating foods containing vitamin B12 e.g.: fish , meat (especially liver), poultry, eggs, milk, and milk products. III- Requirements: - Children 0.9 to 1.8 μg/day. Adults is 2.4 μg/day. Pregnancy is up to 2.8 μg/day. IV- Absorption: 1- Requires intrinsic factor which is a glycoprotein secreted byparietal cells of stomach. 2- Vitamin B12 combines with intrinsic factor forming vitamin B12 - intrinsic factor complex it then reaches the ileum where it is absorbed. 40 3- In the ileum, the complex attaches to a specific receptor and is taken up by the mucosal cell. 4- In the mucosal cell, vitamin B12 is released from its complex & reaches the portal circulation ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2024/2025 2024/2025 2024/2025 Vitamin B12 absorption Deficiency Pernicious anemia Arises when vitamin B12 deficiency impairs the metabolism of folic acid, leading to functional folate deficiency that disturbs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia) Causes: a) Decreased intake of vitamin B12 especially vegetarians. b) Failure of intrinsic factor secretion caused by autoimmune disease affecting parietal cells or c) From production of anti-intrinsic factor antibodies. 41 Drugs induced vitamin B12 deficiency: as neomycin and alcohol.Atrophy of gastric mucosa & defective absorption. *Symptoms & Signs: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 1- The triad of tingling or other skin sensations (paresthesia), tongue soreness (glossitis) and fatigue accompanied by general weakness. 2- Decreased hemopoiesis (macrocytic anemia, leucopenia & thrombocytopenia) 3- In severe cases, the anemia may cause evidence of congestive heart failure, severe chronicform is characterized by subacute combined degeneration of spinal cord, peripheral neuritis 2024/2025 2024/2025 2024/2025 42 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Chapter 4 Carbohydrates Biochemistry 2024/2025 2024/2025 2024/2025 43 Carbohydrates Definition: Carbohydrates are neutral compounds made up of carbon, hydrogen and oxygen. H and O being in the same proportion as in water, the general formula is Cn (H2O)n. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Also, chemically carbohydrates can be defined as: the aldehyde and ketone derivative of higher polyhydric alcohol - 2024/2025 2024/2025 2024/2025 Biomedical Importance of Carbohydrates: 1. Carbohydrates are the main sources of energy in the body. Brain cells and RBCs are almost wholly dependent on carbohydrates as the energy source. Energy production from carbohydrates will be 4 kcal/g. 2. Storage form of energy (starch and glycogen) and. Excess carbohydrate is converted to fat. 3. Glycoproteins and glycolipids are components of cell membranes and receptors. 4. Structural basis of many organisms: Cellulose of plants; exoskeleton of insects, cell wall of microorganisms, mucopolysaccharides as ground substance in higher organisms. 44 5. Deoxy-ribose is a constituent of nucleic acid (DNA), however, Ribose is in RNA. 6. Ribose, i.e. pentose sugar also constituents certain coenzyme, e.g. FAD, NAD, coenzyme A, etc. 7. Glucose is chief physiological sugar present in blood. Classification of Carbohydrates: ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ I. Monosaccharides: (Greek, mono = one; saccharide = sugar). Simplest class of carbohydrates which cannot be further hydrolysed. 2024/2025 2024/2025 2024/2025 1- These are further classified into two groups. On the basis of their functional group they are classified as aldoses and ketoses a. Aldoses: functional group is an aldehyde CH-O b. Ketoses—functional group is a keto group C=O. 2- Monosaccharides can be classified according to the number of carbon atoms into: a.Trioses: monosaccharides containing 3 carbons. b.Tetroses: monosaccharides containing 4 carbons. c.Pentoses: monosaccharides containing 5 carbons. d.Hexoses: monosaccharides containing 6 carbons. e.Heptoses: monosaccharides containing 7 carbons. 45 3- Also, they can be classified according to both presence of aldehyde or ketone groups and number of carbon atoms: a. Aldotrioses and ketotrioses. b. Aldotetroses and ketotetroses. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ c. Aldopentoses and ketopentoses. d. Aldohexoses and ketohexoses. 2024/2025 2024/2025 2024/2025 Formation of Glycosides: Glycosidic bond: It is the bond between a carbohydrate and another compound to form a complex carbohydrate. This bond is between the hydroxyl group of anomeric carbon of monosaccharide (carbon 1 in aldoses or carbon 2 in ketoses) and another compound which may be: 1. Another monosaccharide to form disaccharide glycosides as maltose, lactose and sucrose. 2. Aglycone i.e. non-carbohydrate to form glycoside. Examples: 1. Disacharides, Oligosaccharides, Polysaccharides. 2.Glycolipids & Glycoprotiens. 3.Tannic acid.( digallic acid with glucose). 46 Monosaccharide derivatives 1- Amino Sugars ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Are sugars in which the OH group at C-2 is replaced by an amino group. -Glucosamine, galactosamine and mannosamine which are present together with their N-acetyl derivatives in mucopolysacharides. -Are sugars in which OH group is replaced by H- atom. -The most important example is 2-deoxyribose which is found in DNA. 2024/2025 2024/2025 2024/2025 2- Sugar acids: a-Aldonic acids: Are aldoses in which the aldehyde group is oxidized to carboxyl group. Gluconic acid is the aldonic acid of glucose. b- Uronic acids: Are aldoses in which the primary alcoholic group is oxidized to a carboxyl group. Glucuronic acid is the uronic acid of glucose. c-Aldaric acids: Are aldoses in which both aldehyde and primary alcoholic groups are oxidized to carboxyl groups. Glucaric acid is the aldaric acid of Glucose. 3- Sugar alcohols: Are sugars in which the carbonyl group is reduced to alcohol group. 47 II. Oligosachharides: Definition: These type of carbohydrates are composed of 2-10 monosachharide molecules which can be obtained on hydrolysis. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ The important oligosaccharides are classified depending on number of monosaccharide units. Disaccharides Trisaccharides Tetrasaccharides Pentasaccharides. III. Disaccharides: I. Definition: These are formed by condensation of 2 molecules of monosaccharides bound together by glycosidic bond. Its general formula 2024/2025 is Cn{H2O)n-1. 2024/2025 2024/2025 II. Types: The most important disaccharides are: A-Sucrose 1. Structure: α- D-Glucose and B- D-Fructose connected together through α 1-2 Glucosidic linkage. 2. Sources: Sugar cane, beet cane, table sugar is sucrose, also present in pineapple and carrot 3. It is Hydrolyzed by 2 ways to (Glucose & Fructose): a- Enzymatic: Sucrase (invertase) b- Acid Hydrolysis. 48 B- Lactose 1- Structure: It is formed of one molecule of B-D-galactose with a molecule of D-Glucose. 2- Source: Lactose is the milk sugar. human milk has a concentration of 7g % lactose, also it is ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ the milk sugar of all mammals. 3- It is Hydrolyzed by 2 ways to (Galactose & Glucose): N.B : Lactose is considered a perfect sugar for babies because of : a. It is not fermented, so do not produce gases that cause disturbances to the baby. b. It is not so sweaty, so does not cause nausea and the baby can take its requirements. c. It the only natural source of galactose that enters in structure of galactolipids which are found in great amounts in brain and neves. d. Has a mild laxative effect. 2024/2025 2024/2025 2024/2025 C-Maltose 1- Structure: Maltose is formed by condensation of 2 molecules of α-D- glucose. 2- 2- Sources: a) Malt sugar b) Maltose is produced during digestion of starch by amylase enzyme. 3- Hydrolyzed to 2 molecules of Glucose):. D. Isomaltose: 1- Structure: 2 alpha D glucose 2- Sources: during digestion of starch by mylase enzyme. 3- Hydrolyzed by Isomaltase enzyme. 49 IV.Polysaccharides -Polysaccharides consist of repeated units of monosaccharides or their derivative connected together by glycosidic linkages. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ -They are primarily concerned with two important functions. Structural and storage of energy. -Polysaccharides are of two types: 2024/2025 2024/2025 2024/2025 1-Homopolysaccharides: I. Starch Sources: Main carbohydrate of food. -It exists in cereals (e.g. rice, barley, maize and wheat) and in roots and tubers like potatoes and sweat potatoes. Starch never present in animals. 50 Functions: starch is the main carbohydrate content in our diet. It constitutes about 60% of our daily ingested food. Properties: -Acid hydrolysis of starch: Starch is hydrolysed by heating with a dilute acids to give ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ glucose. -Enzymatic hydrolysis of starch: by salivary amylase (in mouth) the following products are produced. II. Glycogen: (also called animal starch): a.Structure: Glycogen is homopolysaccharide formed of branched α D glucose units -The main glycosidic bond is α1-4- linkage. Only at the branching point, the chain is 2024/2025 2024/2025 2024/2025 attached by α-6 linkage.(similar to amylopectin). b. Location: Glycogen Is present mainly in liver and muscles. c. Functions of glycogen: Liver glycogen: It maintains normal blood glucose concentration especially during the early stage of fast (between meals). After 12-18 hours fasting, liver glycogen is depleted. Muscle glycogen: It acts as a source of energy within the muscle itself especially during muscle contractions. 51 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ III. Cellulose: a.Structure: It is long straight non-branching chains of β-glucose units linked together by β-1-4 glycosidic bond. b.Sources: Cellulose is constitutes the walls of plant cells 2024/2025 2024/2025 2024/2025 c.Properties: Cellulose is insoluble in water. Many mammals including humans cannot digest cellulose of diet because of the absence of digestive hydrolase enzyme that attacks β-linkage. d. Importance: The presence of cellulose in diet is important because it increases the bulk of stool. This stimulates intestinal movement and prevents constipation. IV. Inulin: a. Structure: It is fructosan i.e. formed of repeated units of fructose linked together by β- 1-2 bonds. b. Medical importance: Inulin clearance is one of kidney function tests that measure the of glomerularfiltration rate. 52 ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ Chapter 5 Lipids Biochemistry 2024/2025 2024/2025 2024/2025 53 Definition: Lipids constitute a very important group of organic substances in plants and animals. Chemically they are various types of esters of fatty acids with different alcohols. Properties: Insoluble in water, readily soluble in ether, chloroform and benzene. They are good solvents for fats and fatty acids. ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ These are tasteless, odourless, colourless and neutral in reaction. N.B: The hydrophobic (water-hating) nature of lipids is due to the predominance of hydrocarbon chains (- CH2-CH2-CH2-) in their structure. Biomedical Importance: 1. In diet : Lipids are important constituent of diet due to: a) They are a source of high energyvalue. b) They contain fat soluble vitamins. c) They contain essential fatty acids. d) They make diet palatable. 2. In the body : a) Lipids in adipose tissue serve as storage form of energy. b) They serve as thermal Insulator in the subcutaneous tissues. c) Nonpolar lipids act as electrical insulator, allowing rapid propagation of waves along myelinated nerves. d)2024/2025 Lipoproteins allow fats to move through 2024/2025 2024/2025 the blood, extracellular and intracellular fluids. 54 Fatty Acids 1. Fatty acids are monocarboxylic acids (COOH is polar and charged in PH7). (COOH COO-) 2. They contain large hydrocarbon chain (not polar or not charged) so it is hydrophobic. 3. The most common fatty acids in nature are long chain (more than 12 C) straight even ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ number. 4. Short chain fatty acids (2C, 4C) are soluble while others are insoluble in water. 5. Melting point depends on the length of the chain of fatty acids and degree of saturations. (e.g. short chain fatty acids and unsaturated fatty acids are liquid at room temperature and vice versa). N.B: Numbering of carbon atoms: 2024/2025 2024/2025 2024/2025 N.B: Fatty acids are classified according to several as follows: A- Even and odd number fatty acids. B- Straight and branched chain fatty acids. C- Short (2C, 4C), medium (6C- 12C), long (more than 12C) and very long (more than 20C) chain. D- Saturated and unsaturated fatty acids. * Fatty acid are classified according to Saturation (presence or absence of double bonds) into: A-Saturated Fatty Acids: -They contain no double bonds. -They are solid at room temperature except if they are short chained 55 B-Unsaturated Fatty Acids: They contain double bond & classified to i- Monounsaturated: They contain one double bond. ii-Polyunsaturated (PUFA): ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ a) They contain more the one double bond. b) They are present in liquid state at room temperature. c) They present more in vegetable oils. d) They result in an increase the membrane fluidity. e) They are important for normal growth. f) They decrease the incidence of fatty liver. g) They increase solubility of cholesterol. * Fatty acid are classified according to their nutritional value into: 1) The essential fatty acids: These are polyunsaturated fatty acids (PUFA) which contain more than one double bond. Their essentiality is due to inability of the human body to synthesize them accordingly they must be taken in the diet. 2024/2025 2024/2025 2024/2025 2) Non essential Fatty acids: Synthesized in Body and include all saturated and Mono-unsaturated. ω 3 family — Linolenic acids ω 6 family — Linoleic &Arachidonic acids ω 9 family — Oleic acid ω 7 family — palmitoleic acid 56 Classification Of Lipid ﻣﺤﻤﻮﺩ ﺳﻴﻒ ﺍﻟﻨﺼﺮ ﻋﺒﺪ ﺍﻟﻬﺎﺩﻯ ﺍﻟﺴﻴﺪ 2024/2025 2024/2025 2024/2025 I. Simple Lipids A- Neutral Fats- (Triacylglycerol) These are esters of fatty acids with the tri-hydroxy alcohol, glycerol. They are called neutral because they are uncharged. They include two type: 1. Fats: Solid at ordinary temperature. (more long & saturated F.A). 2. Oils: Liquid at ordinary temperature. (more unsaturated F.A). 57 Occurance of neutral fats: In plants: Cotton seed, olive, Coconut, linseed. sesame & Soya bean oil. In animals: Butter, lard, and animal fats. Marin oils: Cod liver oil and shark liver oil. These oils are v