Water Soluble Vitamins - Biochemistry PDF

Biochemistry Preparatory Year Semester 3 2024 Vitamins (water soluble) Dr. Ohoud Alshehri, PhD Assistant professor in Biochemistry [email protected] Biochemistry Department CLASSIFICATION of VITAMINS (Vitamin B9)...

Biochemistry Preparatory Year Semester 3 2024 Vitamins (water soluble) Dr. Ohoud Alshehri, PhD Assistant professor in Biochemistry [email protected] Biochemistry Department CLASSIFICATION of VITAMINS (Vitamin B9) - Cobalamin (Vitamin B7) (Vitamin B5) Beauty vitamin  Water-Soluble Vitamins Vitamin C Vitamin C = The biologically active form = Ascorbic acid. A. Sources: 1. Fruits especially citrus fruits (lemon, orange), melon, and strawberry. 2. Vegetables especially leafy green vegetables such as lettuce, tomatoes, potatoes, cabbage, and green raw peppers. 3. Guava is very rich in vitamin C. B. Structure: Animal tissues contain 90% L-ascorbic acid and 10% dehydro L- ascorbic acid. Both forms are active.  Water-Soluble Vitamins Vitamin C D. Functions 1- Antioxidant action 2. Formation of collagen protein 3. Absorption and mobilization of iron 4. Coenzyme for many (hydroxylation reaction) hydroxylase enzymes  Functions of Vitamin C 1. Formation of collagen protein: a) Ascorbic acid is essential for the conversion of the procollagen (immature collagen) into collagen. - Procollagen is protein-containing proline and lysine. - Hydroxylation of both amino acids is catalyzed by hydroxylase enzymes and by vitamin C as a coenzyme. - This converts procollagen into collagen. b) Collagen is essential for the synthesis of connective tissue, blood vessels, bone, cartilage, and teeth.  Functions of Vitamin C 2. Absorption and mobilization of iron: Ascorbic acid is a potent reducing agent, keeping iron in the ferrous state Fe+2 3. Ascorbic acid acts as a coenzyme for many hydroxylases enzymes. 4. Antioxidant action: Vitamin C acts as an antioxidant and protects tissues from the toxic effects of some oxidants that may cause cancer. Why human body can't make vitamin C? Most animals require no exogenous vitamin C. For humans, however, vitamin C is an essential vitamin. Humans lack the enzyme L-gulonolactone oxidase, and people must ingest it. Therefore, vitamin C deficiency and its manifestations have largely been a product of inadequate dietary intake.  Risk factors for Vitamin C deficiency 1. Alcoholism 2. Babies only fed cow's milk 3. Seniors only consuming tea and toast diet 4. Poor people who are not able to afford fruits and vegetables 5. Smokers 6. Individuals with eating disorders 7. Type 1 diabetes who have high vitamin C requirements 8. Individuals with disorders of the GI tract like inflammatory bowel disease. 9. Individuals with iron overload, which leads to wasting of vitamin C by the kidneys 10. Individuals with restrictive diets, food allergies https://www.ncbi.nlm.nih.gov/books/NBK493187/  Deficiency of Vitamin C E. Deficiency: → (scurvy) It is characterized by: 1. Manifestations due to decreased collagen formation: a) Bleeding into to gum, muscles, joints, kidneys, gastrointestinal tract, and pericardium. b) Defective formation of bone and teeth. c) Defective healing of wounds. 2. Anemia: due to decreased absorption of iron and bleeding. 3. Manifesations due to decreased neurotransmitters (epinephrine and norepinephrine ) a) Behavioral changes. b) Severe emotional disturbances. c) General weakness. Scurvy  Water-Soluble Vitamins Vitamin C Requirements: 90 mg/d for men and 75 mg/d for women. https://www.ncbi.nlm.nih.gov/books/NBK225480/ B complex B Vitamins  B Complex vitamins A. Introduction: The B complex are a group of vitamins of different chemical molecules. They are put together in one group because: 1. All are soluble in water. 2. All are present in the same sources. B vitamins are particularly abundant in whole grain cereals, liver, and yeast. 3. Deficiencies of B vitamins are often multiple rather than singular. Due to their presence in the same foods. B. Functions of vitamin B complex: 1. All vitamins as coenzymes enzymatic reactions. 2. Folic acid and B12 act as coenzymes in hematopoiesis (formation of red blood cells)  B Complex vitamins C. Absorption and storage of vitamin B complex: 1. Absorption: The B vitamins are absorbed in the intestine and transported in the portal circulation. 2. The tissue stores of most B vitamins are minimal. The depletion occurs over several weeks in response to dietary restriction or increased requirements as in pregnancy. Body stores of folic acid and vitamin B12 are more extensive than other B vitamins. D. Toxicity of vitamin B complex: Toxic effects are relatively uncommon since excessive ingestion of water-soluble vitamins is followed by saturation of body stores and rapid loss of excess vitamins in the urine.  Thiamine (Vitamin B1) Antiberiberi factor,antineuritic (preventing or relieving inflammation of a nerve) vitamin A. Sources: 1. Whole grain cereals, legumes, and yeast. 2. Unpolished rice and whole wheat bread. B. Structure: 1. Thiamine consists of a substituted pyrimidine ring connected to a substituted thiazole ring through a methylene bridge. 2. Active form of B1 = Thiamine diphosphate (TPP): a) It is also called thiamine pyrophosphate. b) Formation of TPP needs thiamin kinase enzyme, which is present in the liver, red cells, and nervous tissue. 3. TPP Formed by the transfer of a pyrophosphate group from adenosine triphosphate (ATP) to thiamine. Functions of B1 (TPP) C. Functions 1. TPP acts as a coenzyme in two separate reactions in carbohydrate metabolism. These are A. Oxidative decarboxylation of a-ketoacids: 1) Pyruvate by Pyruvate dehydrogenase enzyme. 2) a-ketoglutarate by a-ketoglutarate dehydrogenase. 3) Ketoacids of branched-chain amino acids; Valine, leucine, and isoleucine) B. Transketolation reactions: by transketolase, in pentose phosphate pathway (HMP hexose monophosphate shunt pathway). 2. Nerve conduction: Thiamin is also essential for the process of nerve conduction and the structure of the nerve membrane. https://www.sciencedirect.com/topics/agricultural-and-biological- sciences/thiamine-pyrophosphate  Thiamine (Vitamin B1) D. Storage: - The capacity to store is limited. - It is present in both free and combined forms in the heart (highest concentration), Liver, and kidneys. - In lower concentration in skeletal muscle and brain. - Total amount of Thiamine in the body is approximately 25 mg. E. Excretion: If a normal amount of thiamine is taken in the diet: About 10 percent is excreted in the urine The remainder is : - Partly phosphorylated and used as coenzyme. - Partly degraded to neutral Sulphur compounds and inorganic SO4 which are excreted in urine.  Thiamine (Vitamin B1) F. Recommended Dietary Allowance Thiamine Recommendations RDA Men: 1.2 mg/day RDA Women: 1.1 mg/day  Beriberi G. Deficiency: → Beriberi Clinical indications for thiamine: Thiamine deficiency is diagnosed by an increase in erythrocyte transketolase activity observed on addition of thiamine pyrophosphate. TPP Impaired carbohydrate metabolism. This lead to → ↓ Energy production → Impaired cellular functions especially of the nervous system → Beriberi This is a severe thiamine-deficiency syndrome found in areas where polished rice is the major component of the diet. Signs of infantile beriberi include tachycardia, vomiting, convulsions, and, if not treated, death. The deficiency syndrome can have a rapid onset in nursing infants whose mothers are deficient in thiamine. Adult beriberi is characterized by dry skin, irritability, disordered thinking, and progressive paralysis.  Beriberi Types of beriberi: a) Dry beriberi: (Wernicke- Korsakoff syndrome) characterized by: 1) Peripheral neuritis. 2) Muscle wasting and hyperesthesia (sensitivity to different sensations, such as pain, heat, etc.). 3) loss of nerve transmission (Polyneuritis) due to degeneration of the myelin in the muscular sheaths b) Wet beriberi: characterized by: 1)Heart failure. 2) Edema 3) Oral manifestations: Satin like appearance of tongue and gingiva (atrophy of filliform papillae), angular cheilosis https://www.ncbi.nlm.nih.gov/books/NBK114331/ B Vitamins  Riboflavin (Vitamin B2) A. Sources: 1. Milk and milk products. 2. Eggs, liver, and green leafy vegetables. B. Structure: It is formed of flavin ring attached to ribitol (alcohol of ribose sugar).  Riboflavin (Vitamin B2) C. Active forms of riboflavin (B2): 1. FMN: Riboflavin enters in the structure of flavin mononucleotide and flavin adenine dinucleotide (FAD). 2. FAD: is formed by phosphorylation of riboflavin by ATP (by intestinal flavi okinase enzyme). FAD is formed by the transfer of an AMP moiety from ATP to FMN.  Riboflavin (Vitamin B2) D. Functions of B2: 1. Formation of FMN & FAD a) Both FMN and FAD are coenzyme for flavo enzymes. b) They act as hydrogen (or electron) carriers in oxidation- reduction reactions → FMNH2 and FADH2. (Examples) 2. Oxidation-reduction reactions 3. Electron transport chain 4. Citric Acid/TCA Cycle 5. Catabolism of fatty acids  FAD and FMN Flavin adenine dinucleotide (FAD) is a coenzyme for: Cytochrome-b5 reductase, the enzyme that maintains hemoglobin in its functional reduced state Glutathione reductase, an enzyme that also protects erythrocytes from oxidative damage. Flavin mononucleotide (FMN) A coenzyme for a number of oxidative enzymes including NADH DEHYDROGENASE. It is the principal form in which RIBOFLAVIN is found in cells and tissues. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/flavin-adenine-dinucleotide https://pubchem.ncbi.nlm.nih.gov/compound/Flavin-mononucleotide Riboflavin Recommendations RDA Men: 1.3 mg/day RDA Women: 1.1 mg/day  Deficiency of Riboflavin E. Deficiency: B2 deficiency is not fatal. Deficiency causes by Low milk/dairy intake Alcoholics Long term phenobarbital ( drug) use It is characterized by: 1. Ocular disturbances: a) Photophobia i.e. abnormal sensitiveness of the eye to the light. b) Vascularization of the cornea. 2. Cheilosis (fissuring at the corners of the mouth). 3. Ariboflavinosis, Glossitis i.e. inflammation of the tongue, which appears smooth and purplish. 4. Dermatitis i.e. inflammation of the skin. Ariboflavinosis B Vitamins  Niacin (nicotinic acid, B3) A. Sources: 1. Whole grain cereals. 2. Milk, meat, liver, egg, and yeast. a) Niacin can be synthesized endogenously from the tryptophan amino acid. b) Meat is rich in tryptophan, so it is an important source of niacin. B. Structure: 1Niacin (= nicotinic acid) is a pyridine derivative. C. Active forms: 1. NAD+ and NADP+ : Niacin is converted to the active form nicotinamide that enters the structure of nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). 2. Nicotiamide, a derivative of nicotinic acid contains amide group.  Niacin (nicotinic acid, B3) Synthesis of NAD+ and NADP + The formation of NAD+ and NADP+ occurs in the cytosol of liver cells.  Functions of niacin E. Functions of niacin: 1. Formation of (NAD+) and (NADP+): Niacin is essential for the formation of the coenzymes nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). a) They function as hydrogen carrier coenzymes in oxidation-reduction reactions. b) These reactions are important in carbohydrate, protein, and lipid metabolism. 2. Lowering plasma cholesterol: by inhibiting the flow of free fatty acids (FFA) from adipose tissue which provides acetyl COA molecules essential for cholesterol and triacylglycerol synthesis. Niacin raises HDL levels  Niacin Recommendations The body can obtain niacin from dietary niacin and dietary tryptophan (60 mg of dietary tryptophan = 1 mg niacin); therefore niacin intake is measured in niacin equivalents (NE). – RDA Men: 16 NE/day – RDA Women: 14 NE/day  Deficiency of Niacin Deficiency: → Pellagra 1. Pellagra, the disease affects the skin, gastrointestinal tract, and central nervous system CNS. 2. Manifestations of pellagra: a) Pellagra is called a disease of (4 D): diarrhea, dermatitis, dementia, and if not treated death. 3. Causes of pellagra: a) Deficiency of niacin, tryptophan, or vitamin B6. b) Corn is deficient in both niacin and tryptophan. Thus people who depend on corn as a major source of protein as some farmers develop pellagra. c) Hartnup's disease: It is a hereditary disease in which there is a defect in tryptophan absorption from the intestine and tryptophan re-absorption by renal tubules → pellagra. d) Argentaffinoma (malignant carcinoid syndrome): In which large quantities of tryptophan are converted to serotonin. B Vitamins  Pyridoxine “vitamin B6" A. Sources: Wheat, corn, egg yolk, liver, and meat. B. Structure Vitamin 6 includes a group of vitamers from the pyridine ring (pyridoxine, pyridoxal, and pyridoxamine). Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are found in foods obtained from animals. The coenzyme forms of vitamin B6: (pyridoxal phosphate [PLP] and pyridoxamine phosphate [PMP]) are involved in: amino acid and fatty acid metabolism, the conversion of tryptophan to niacin or serotonin, and the production of red blood cells. C. Vitamin B6 Recommendations RDA Adults 19-50 years: 1.3 mg/day  Functions of Pyridoxine D. Functions: In the body, pyridoxine is converted to pyridoxal phosphate, which acts as a coenzyme for a large number of enzymes: 1. In protein metabolism: It acts as a coenzyme for amino acids metabolism in the following reactions: a) Transamination b) Trans-sulfuation c) Deamination d) Decarboxylation e) SYNTHESIS OF: Heme synthesis, Vitamin B3 (niacin) synthesis, and Sphingosine synthesis. f) It takes a role in amino acids absorption from the intestine. 2. In carbohydrate metabolism: Pyridoxal phosphate acts as a coenzyme of glycogen phosphorylase Glycogen breakdown Into glucose (glycogenolysis). 3. In lipid metabolism: Pyridoxal phosphate is Important in steroid hormone action.  Deficiency of “vitamin B6" E. Deficiency: 1. Isoniazid: It is a drug that is used in (treatment of tuberculosis. Isoniazid binds with B6 - Excretion by kidney - pellagra. 2. Convulsions in young infants due to deficient formation of GABA (inhibitory transmitter in the brain). 3. Anemia (microcytic and hypochromic) due to deficient formation of heme and hemoglobin. 4. Disturbance in amino acids metabolism. This leads to growth retardation and maybe mental retardation. 5. Breast, uterus, and prostate cancer: due to defective action of B6 on steroid – DNA binding.  Toxicity of pyridoxine Pyridoxine is the only water-soluble vitamin with significant toxicity. Neurologic symptoms (sensory neuropathy) occur at intakes above 200 mg/day, an amount more than 100 times the RDA. Substantial improvement, but not complete recovery, occurs when the vitamin is discontinued.  Video https://www.youtube.com/watch?v=ISZLTJH5lYg Reference Lippincott 8th edition Chapter 28