Lecture 13 Vitamins Notes PDF

Enzymes and Vitamins Vitamins and Coenzymes  Function of Co-enzymes n A co-enzyme prepares the active site for catalytic activity.  Water-Soluble Vitamins Water-soluble vitamins are: n Soluble in aqueous solutions. n Used as cofactors by many enzymes. n Not stored in the body. ...

Enzymes and Vitamins Vitamins and Coenzymes  Function of Co-enzymes n A co-enzyme prepares the active site for catalytic activity.  Water-Soluble Vitamins Water-soluble vitamins are: n Soluble in aqueous solutions. n Used as cofactors by many enzymes. n Not stored in the body.  Thiamin (Vitamin B1) Thiamin: n Was the first B vitamin identified. n Is part of the coenzyme thiamin pyrophosphate. n TPP coenzyme is required by enzymes in the decarboxylation of a-keto carboxylic acids. n Deficiency results in beriberi (fatigue, weight loss, and nerve degeneration).  Riboflavin (Vitamin B2) Riboflavin is: n Made of the sugar alcohol ribitol and flavin. n Part of the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). n Needed for good vision and healthy skin. O H3C N H N H3C N N O D-Ribitol CH2 CH CH CH CH2 OH OH OH OH  Niacin (Vitamin B3) Niacin: n Is part of the coenzyme O nicotinamide adenine C dinucleotide (NAD+) OH involved in oxidation- reduction reactions. N n Deficiency can result in dermatitis, muscle fatigue, and loss of appetite. n Is found in meats, rice, and whole grains.  Pantothenic Acid (Vitamin B5) Pantothenic acid: n Is part of coenzyme A needed for energy production as well as glucose and cholesterol synthesis. n Deficiency can result in fatigue, retarded growth, cramps, and anemia. n Is found in salmon, meat, eggs, whole grains, and vegetables. CH3 OH O O HO CH2 C CH C N CH2 CH2 C OH CH3 H  Pyridoxine (Vitamin B6) n Pyridoxine and pyridoxal are two forms of vitamin B6, which are converted to the coenzyme pyridoxal phosphate (PLP). n PLP is required in the transamination of amino acids and decarboxylation of carboxylic acids. n Deficiency of pyridoxine may lead to dermatitis, fatigue, and anemia.  Cobalamin (Vitamin B12) Cobalamin: n Consists of four pyrrole rings with a Co2+. n Is a coenzyme for enzymes that transfer methyl groups and produce red blood cells. n Deficiency can lead to pernicious anemia and nerve damage. n Pernicious anemia (PA) is an auto-immune disorder in which the body fails to make enough healthy red blood cells (RBCs). n The most common cause of pernicious anemia is the loss of stomach cells that make intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. The loss of parietal cells may be due to destruction by the body's own immune system.  Ascorbic Acid (Vitamin C) Vitamin C: n Is required in collagen synthesis. n Deficiency can lead to weakened connective tissue, slow-healing wounds, and anemia (scurvy). CH2OH O n Is found in blueberries, O CHOH citrus fruits, tomatoes, broccoli, red and green HO OH vegetables.  Folic Acid (Folate) Folic acid (folate): n Consists of pyrimidine, p-aminobenzoic acid, and glutamate. n Forms the co-enzyme THF (tetrahydrofolate) used in the transfer of carbon groups and the synthesis of nucleic acids. n Deficiency can lead to abnormal red blood cells, anemia, and poor growth.  BIOTIN Biological function: Biotin functions as a co-enzyme in those tissue reactions involving the transfer of CO2 from one compound to another (ie. carboxylation reactions). For example, as a component of the enzymes pyruvate carboxylase and acetyl CoA carboxylase, biotin is responsible for the conversion of pyruvic acid to oxaloacetic acid (an intermediate in gluconeogenesis and the krebs cycle), and for the conversion of acetyl CoA to malonyl CoA (the latter required for the synthesis of long chain fatty acids). Biotin therefore plays a key role in carbohydrate and fat metabolism Biotin is also reported to be involved in purine and protein synthesis, certain deamination reactions, and in the urea cycle; however, the precise role of biotin in most of these actions is still unclear. Dietary sources: Rich dietary sources of biotin include: dried brewers yeast, dried torula yeast, dried distillers solubles, rapeseed meal, safflower seed meal, sunflower seed meal (2-1 mg/kg); whole hens egg, rice polishings, dried brewers grains, liver and lung meal, rice bran, dried delactose whey, cottonseed meal (1–0.5 mg/kg); groundnut meal, soybean meal, dried skim milk, alfalfa meal, oats, sorghum, dried blood meal, dried fish solubles, fish meal, wheat bran, wheat mill run (0.5-0.2 mg/kg). Other rich sources of biotin include the legumes and green vegetables.  Fat-Soluble Vitamins Fat-soluble vitamins: n Are A, D, E, and K. n Soluble in lipids, but not in aqueous solutions. n Important in vision, bone formation, antioxidants, and blood clotting. n Stored in the body.  Vitamin A n Vitamin A is obtained from meats and beta- carotenes in plants. n Beta-carotenes are converted by liver enzymes to vitamin A (retinol). Beta-carotene H3C CH3 CH3 H3C CH3 H3C CH3 CH3 CH3 CH3 CH3 CH3 H3C CH3 CH2OH Retinol (vitam in A) CH3  Vitamin D Vitamin D (D3): n Is synthesized in skin exposed to sunlight. n Regulates the absorption of phosphorus and calcium during bone growth. n Deficiency can result in weakened bones. n Sources include cod liver oil, egg yolk, and enriched milk.  Vitamin E Vitamin E: n Is an antioxidant in cells. n May prevent the oxidation of unsaturated fatty acids. n Is found in vegetable oils, whole grains, and vegetables. CH3 HO CH3 CH3 CH3 CH3 H3C O CH3 CH3  Vitamin K n Vitamin K1 in plants has a saturated side chain. n Vitamin K2 in animals has a long unsaturated side chain. n Vitamin K2 is needed for the synthesis of zymogens for blood clotting. O O CH3 CH3 CH3 CH3 3 n O CH3 CH3 O CH3 CH3 Vitamin K 1 (phylloquinone) Vitamin K 2 (menaquinone)  Clinical Example Case Study: Hepatitis n A 36-year old man was admitted to a hospital following episodes of nausea, vomiting, and general malaise. n His urine was darker than usual. n Upon examination it was discovered that his liver was enlarged and tender to palpation. n Liver function tests were abnormal; plasma ALT was 1500 IU/L (Alanine aminotransferase 6.0 – 21 U/L); AST was 400 IU/L (Aspartate aminotransferase 7.0 – 20 U/L). n During the next 24 hours the man developed jaundice, and his plasma total bilirubin was 9.0 mg/dL (0.2 – 1 mg/dL). n A diagnosis of hepatitis was made.  Bilirubin n Biliribin is derived from the breaking down of the hemoglobin of aging red blood cells n Bilirubin is insoluble in water; to be excreted it is converted to a water-soluble bilirubin diglucuronide in the liver n The first formed “indirect” bilirubin is bound to albumin and rapidly transported in plasma to the liver; albumin is not taken into the liver cells n “Direct” bilirubin (water soluble) is secreted into the bile canaliculus, together with other bile constituents and is collected in the gallbladder n Some of the bile pigments are excreted in the feces and some water soluble bilirubin (not free bilirubin) is excreted by the kidney into the urine  Bilirubin continued: n In hepatitis, the formation of water soluble bilirubin is less efficient n The secretion of “direct” bilirubin (water soluble bilirubin) into the bile canaliculi is impaired n The result is a backing-up of the bilirubin excretion with a build-up of total bilirubin in the blood. n The initial increase is expressed as a darkened urine, followed by jaundice