Biochemistry Unit 9 Vitamins.pdf

BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Define a vitamin and classify vitamins as water soluble or fat soluble List the vitamin B complex and identify the major functions of each vitamin in t...

BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Define a vitamin and classify vitamins as water soluble or fat soluble List the vitamin B complex and identify the major functions of each vitamin in the body Identify the major deficiency disease associated with each vitamins  VITAMINS Organic molecules that are essential for normal health and growth Required in trace amounts and must be obtained from the diet because they are not synthesized in the body The vitamins are mainly classified into two: Fat soluble vitamins Water soluble vitamins Fat soluble vitamins  Vitamin A Vitamin A occurs in two forms: 1. Preformed (active form) Retinoids (retinol, retinal & retinoic acid) Found in animal tissues 2. Provitamin A Carotenoids (β-carotene) Found in plant tissues Converted to retinoids form (retinal) β-ionone ring  All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached  In the intestinal mucosa, two molecules of retinal are formed from one molecule of β-carotene  Intestine is the major site of absorption Within the mucosal cell, the retinol is re-esterified with FAs, incorporated into chylomicrons (retinyl esters), transported to liver and stored as retinyl palmitate Vitamin A from liver is transported to peripheral tissues as trans-retinol by the retinol binding protein (RBP) Rhodopsin - membrane protein found in photoreceptor cell of retina  Function of Vitamin A Vision The 11-cis-retinal bound to the protein opsin forms rhodopsin, which when bleached by light, triggers a nerve impulse from the optic nerve to the brain Reproduction Antioxidant The anticancer activity has been attributed to the natural antioxidant property of carotenoids Growth (skeletal growth) Normal functioning of osteoblast and osteoclast Maintain integrity of epithelial cells  Vitamin A Deficiency Night blindness Bitot's spots Xerophthalmia The conjunctiva becomes dry, thick and wrinkled. The conjunctiva gets keratinized and loses its normal transparency. Dryness spreads to cornea Keratomalacia (softening of the cornea) When xerophthalmia persists for a long time, it progresses to keratomalacia. There is degeneration of corneal epithelium which may get vascularized and corneal opacities develop  Vitamin D Is called the “sun-shine vitamin” Vitamin D is derived either from 7-dehydrocholesterol or ergosterol by the action of UV radiations Active form of vitamin D: 1,25-dihydroxycholecalciferol (calcitriol) Deficiency diseases Rickets (children) & osteomalacia (adults) Bowed legs (knee bent out) Rickets Vitamin D Metabolism  Function of Vitamin D Action of calcitriol on the: 1. Intestine Increases the intestinal absorption of calcium & phosphate By increased synthesis of calcium binding protein 2. Bone Causes mobilization of calcium and phosphate from the bone and promotes bone demineralization 3. Kidney Promotes reabsorption of calcium and phosphorus → decreases excretion of calcium and phosphorus  Vitamin E Exists in eight chemical forms Tocopherol (α-, β-, γ-, δ-) Tocotrienol (α-, β-, γ-, δ-) Active form: α-tocopherol Most potent biological antioxidant Prevents free radical damage to polyunsaturated fatty acids, particularly those in the cell membrane of RBCs Reduces oxidative damage to LDLs Deficiency: Hemolytic anemia, peripheral neuropathy, increased risk of cardiovascular diseases  Vitamin K Exists in two natural forms: Vitamin K1 (phylloquinone) & vitamin K2 (menaquinone) Vitamin K3 (menadione) is a synthetic analogue Vitamin K is necessary for coagulation of blood Vitamin K → cofactor for synthesis of γ-carboxyglutamic acid (Gla) Formation of Gla is a post-translational modification required for activation of clotting factors II, VI, IX and X Vitamin K plays a role in bone growth & development Deficiency: Hemorrhagic disease, osteoporosis Water soluble vitamins  Vitamin C (Ascorbic acid) Most animals can synthesize ascorbic acid from glucose via uronic acid pathway but human cannot synthesize vitamin C due to deficiency of L-gulonolactone oxidase Functions: Hydroxylation of proline & lysine which is needed for cross-linking in structure of collagen (major component of connective tissue) Antioxidants Enhance iron absorption from intestine Role in tryptophan & tyrosine metabolism Synthesis of bile acid from cholesterol  Deficiency: Impaired synthesis of collagen leads to scurvy characterized by bleeding gums, bruising and poor wound healing Anemia Hemorrhagic tendency  Vitamin B1 (Thiamine) Active form: Thiamine pyrophosphate Biochemical functions: Cofactor for pyruvate dehydrogenase in the link reaction between glycolysis & Krebs cycle. Involved in energy metabolism from TPP transferase glucose & other carbohydrates Cofactor for α-ketoglutarate dehydrogenase Cofactor for α-ketoacids dehydrogenase Cofactor for transketolase in the pentose phosphate pathway  Thiamine Deficiency Beriberi (weakness) 1. Wet beriberi Symptoms: edema, difficulty in breathing & ultimately congestive heart failure 2. Dry beriberi Symptoms: peripheral neuropathy (diminished sensation & weakness in the legs & arms), muscle pain & tenderness  Wernicke-Korsakoff syndrome (associated with alcohol abuse) Nystagmus (abnormal movement of eye) Psychosis Dementia Abnormal gait  Vitamin B2 (Riboflavin) Active forms: Flavin mononucleotide (FMN) & Flavin adenine dinucleotide (FAD) Flavin coenzymes are involved in mitochondrial respiratory chain, fatty acid and amino acid oxidation and citric acid cycle Deficiency: glossitis, cheilosis, angular stomatitis, corneal vascularization  Vitamin B3 (Niacin) Active forms: Nicotinamide adenine dinucleotide (NAD+) & nicotinamide adenine dinucleotide phosphate (NADP+) NAD+ is important as a “hydrogen carrier” for ATP production by the respiratory chain, whereas NADP+ is very important for biosynthetic reactions (e.g. lipid synthesis) The precursors of NAD+ are vitamin B3, nicotinamide and tryptophan  Deficiency: Pellagra (rough skin) Demetia (loss of memory, inability to concentrate) Diarrhea (with blood & mucus in stools) Dermatitis (scaly, dark pigmented rash) Death (if untreated)  Vitamin B7 (Biotin) Acts as coenzyme for carboxylation reactions (fatty acid synthesis & gluconeogenesis) Consumption of raw egg white for a prolonged period may cause biotin deficiency as it contains a protein avidin, which strongly binds biotin and prevents its absorption from the intestine Deficiency: dermatitis, atrophic glossitis, hair loss, muscle pain, anorexia and hallucinations  Vitamin B5 (Pantothenic Acid) As a component of coenzyme A (CoA) which has numerous functions in carbohydrate, lipid and amino acid metabolism Tricarboxylic acid (TCA) cycle and gluconeogenesis Synthesis of fatty acid, cholesterol and steroid hormones Acetylcholine, melatonin synthesis Heme synthesis Ketone body synthesis and utilization Deficiency: burning foot syndrome is manifested as paresthesia (burning, lightning pain) in lower extremities, staggering gait due to impaired coordination and sleep disturbances  Vitamin B6 (Pyridoxine) Exists naturally in three forms: pyridoxine, pyridoxal & pyridoxamine Active form: pyridoxal phosphate (PLP) PLP acts as a coenzyme for: Transamination: aspartate + α-ketoglutarate → glutamate + oxaloacetate Deamination: serine → pyruvate Formation of cysteine from methionine Heme synthesis: aminolevulinic acid (ALA) synthase Decarboxylation reactions of amino acids Deficiency: Neurological manifestation: seizures, depression, confusion, peripheral neuropathy E.g. In infants, pyridoxine deficiency can predispose to seizures: This may be due to decreased formation of γ- aminobutyric acid (GABA) from glutamic acid (decarboxylation reaction). GABA is an inhibitory neurotransmitter, so its decreased concentration can lead to seizures Dermatological manifestation: pellagra Haematological manifestation: hypochromic microcytic anemia