Section 10: Nutrients and their functions

1. Section 10: Nutrients and their functions • B vitamins 02/03/06

2. The water soluble B-complex vitamins and several related non-vitamins are carriers in group transfer reactions. Entity Transferred Coenzyme Vitamin electron (H’) NAD, NADP niacin (nicotinamide) electron (H’) FMN, FAD riboflavin (B2) electron (H’) coenzyme Q - electron heme derivatives - aldehyde thiamine pyrophosphate thiamine (B1) acyl group coenzyme A pantothenic acid acyl group, electron lipoyl (-enzyme) - alkyl group coenzyme B12 B12 (cobalamine) carbon dioxide biotin (-enzyme) biotin amino group pyridoxal phophate pyridoxine (B6) methyl, methylene, tetrahydrofolate folic acid (folate) or formyl group B Vitamins 1

3. Overview of B Vitamin Deficiency • Early studies of beriberi and pellagra focused on something present in starch that caused the diseases. Later it was learned that the symptoms were due to something missing. • The B-complex vitamins are missing in refined foods (white bread, white rice), which have had the metabolically active portions of the whole grain removed. • These vitamins are cofactors for a large number of reaction schemes that derive energy from food and produce essential biosynthetic intermediates and products. • The symptoms of deficiencies are not unique, and it is difficult to assign a given symptom to a particular missing vitamin. • Currently, refined foods typically have the B-complex vitamins added back, and deficiencies are seen only among those with the most impoverished diets. 2

4. Niacin • RDA = 15 & 19 mg (F&M). • The vitamin niacin is converted to nicotinamide and incorporated into electron carriers for catabolic and anabolic metabolism. • Deficiency, when its precursor tryptophan is also low, leads to pellagra (dermatitis, stomatitis, glossitis). 3

5. Riboflavin • RDA = 1.3 & 1.7 mg (F&M). • Incorporated into electron carriers (free and protein-bound). • Deficiency leads to cheilosis. 4

6. Coenzyme Q • Not a vitamin. • An electron carrier in the mitochondrial inner membrane. 5

7. Heme Derivatives • Hemes are not vitamins. • They have roles as electron carriers and oxygen carriers. 6

8. Thiamine • RDA = 1.1 & 1.5 mg (F&M). • The vitamin thiamine is pyrophosphorylated to make a coenzyme for several aldehyde transfer reactions in carbohydrate metabolism. • Deficiency causes beriberi (light-sensitive weak eyes, purple tongue). 7

9. Pantothenic Acid • Safe and adequate daily dietary intake = 4 - 7 mg. • The vitamin is incorporated into coenzyme A and acyl carrier protein of the fatty acid synthase complex. • No deficiencies known. 8

10. Lipoic Acid • Not a vitamin. • Lipoic acid is covalently attached to active sites by a peptide linkage to a lysine. • An acyl and e- carrier. 9

11. Cobalamin • RDA = 2 mg (F&M). • Absent in plants. • Required for methyl transfers, DNA synthesis, succinyl CoA synthesis. • Deficiency, almost always due to inadequate production of a glycoprotein (intrinsic factor) in the stomach lining, causes pernicious anemia. 10

12. Biotin • Safe and adequate daily dietary intake = 30 - 100 mg (F&M). • Required for CO2transfers, malonyl CoA synthesis, oxaloacetate synthesis. • Deficiency rare, although it can be induced by high levels of avidin in the diet, because avidin binds biotin very tightly. 11

13. Pyridoxine • RDA = 1.6 & 2.0 mg (F&M). • The vitamin, pyridoxine, is oxidized and phosphorylated. • Required for various reactions involving amino groups. 12

14. Folic Acid • RDA = 180 & 200 mg (F&M). • Required for single carbon transfers, purine biosynthesis. • Deficiency leads to anemia. 13

15. Choline • Choline is not a vitamin or a carrier. • It is a source methyl groups and is recommended in the diet. • It has lipotropic effects due to its role in phospholipid metabolism. 14

16. Conversion of Pyruvate to Acetyl CoA • Pyruvate dehydrogenase complex catalyzes these reactions, which require several vitamin-derived coenzymes. (section 6 lecture 4) • Thiamine pyrophosphate is bound to the active site by NCI’s. • Covalently bound lipoamide is reduced when acetyl group forms. • Coenzyme A is a substrate. • NAD+ is required to oxidize lipoamide back to the disulfide state. 15

17. Oral Manifestations of Avitaminosis DISEASE CLINICAL SYMPTOMS BIOCHEMICAL LESION NUTRIENT Rickets enamel hypoplasia* inadequate synthesis vitamin D of calcium binding protein by intestinal cells Beriberi magenta tongue**, impaired carbohydrate thiamine (B1) angular cheilosis metabolism; many oxidative decarboxylations cannot occur Scurvy loose teeth, proper collagen ascorbate (C) bluish-red not made; other gingivitis, hydroxylations bleeding at do not occur gums Pellagra stomatitis, impaired carbohydrate niacin glossitis**, metabolism and electron cheilosis transport due to reduced NAD+ 16

18. Oral Manifestations, con’t. DISEASE CLINICAL SYMPTOMS BIOCHEMICAL LESION NUTRIENT none named stomatitis, Impaired carbohydrate riboflavin (B2) glossitis**, metabolism and electron cheilosis transport due to reduced FAD none named stomatitis impaired amino pyridoxine (B6) acid metabolism Megaloblastic stomatitis, impaired DNA synthesis folate anemia glossitis**, due to reduced thymine (Sprue) cheilosis production Pernicious glossitis Impaired methyl group vitamin B12 anemia transfers *Enamel hypoplasia is caused also by vitamin A deficiency during tooth development, or by chronic renal failure-induced decrease in 1,25-dihydroxycholecalciferol production. **It is often difficult to distinguish glossitis, magenta tongue (an archaic term) or red beefy tongue as symptoms. Any one can indicate systemic problems due to iron deficiency or multiavitaminosis. 17

19. Food Pyramid (USDA 1996) • Heavy reliance on carbo-hydrates. • Less than 30% calories from fats & oils. • Aims for cardio-vascular health. • Too many servings? Revised 1996 18

20. Revised Food Pyramid (USDA 2005) Revised 1996 Revised 2005 For 2000 cal/day Exercise ~30 min/day More fruits, vegetables, nuts, seeds, and legumes. Less fat, oil, sugar, and meats. Whole grains. Exercise. Fats, oils, 2-3/wk ! Sweets, 5/week Low-fat or fat-free, 2-3 Meat, poultry, fish, 2 or less Nuts, seeds, legumes, 4-5 4-5 4-5 Whole grain 7-8 19

21. Study indicates reduced risks of major chronic diseases. • Healthy eating index (HEI) evaluates carbohydrates, fats and oils. • Very low in animal fats and refined starch. • High in fish and vegetable oils. • Notice exercise at base. • From McCullogh etal (2002) American Journal of Clinical Nutrition 76:1261. Healthy Eating Pyramid (alternative to USDA pyramid) 20

22. Fat and Heart Disease Locale Fat Calories Rate of HeartPercent of Total Disease* Japan 10 500 Eastern Finland 38 3,000 Crete 40 200 *Incidence of coronary heart disease per 10,000 men over ten year period. What kind of fat is more important than percent calories from fat. Willett & Stampter (2002) Scientific American 288:64-71. 21

23. Fast Food Analysis From http://nat.crgq.com/mainnat.html No snacks! 22

24. Next topic Extracellular Macromolecules: Glycosaminoglycans; proteoglycans; mucins