Water-Soluble Vitamins - Nutritional Biochemistry PDF

Nutritional Biochemistry and Nutraceutics AA 2024/2025 Water-soluble vitamins Prof. Cristina Angeloni Single cycle degree in...

Nutritional Biochemistry and Nutraceutics AA 2024/2025 Water-soluble vitamins Prof. Cristina Angeloni Single cycle degree in Pharmacy Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Copyright notice The contents of this lesson are subject to copyright and intended only for personal use by students enrolled in courses offered by the University of Bologna. For this reason, any partial or total reproduction, adaptation, modification and/or transformation of the contents of this lesson, by any means, without the prior written authorization of the copyright owner, is strictly prohibited. Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamins From the Latin amine of life Organic substances of different chemical nature required in small quantities (mg or μg ) for cellular metabolism They are essential In the organism they have the important function of bioregulators Their deficiency leads to the appearance of pathological symptoms that gradually progress with malnutrition and rapidly regress following the intake of the missing vitamin Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamins... do all species need them? Not all vitamins are required for each animal species: a substance that is a vitamin for one species may not be a vitamin for another. For example, we and a few other species need Vitamin C because we are unable to synthesize it due to the mutation of an enzyme of the biosynthetic pathway (gulonolactone oxidase). 4 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Possible causes of deficiency LACK OF SUPPLY Exclusion of foods from the diet Insufficient food ration Wrong eating habits Unbalanced low calorie diets Anorexia Incorrect cooking of food Food taboos ABSORPTION DISORDERS Alcoholism Digestive disorders Prolonged drug therapies INCREASE IN NEEDS Growth period Pregnancy Feeding time Intense physical activity Use of drugs INCREASE OF ELIMINATION Feeding time Excessive sweating Increased diuresis  HYPERVITAMINOSIS Hypervitaminosis problems do not exist with normal nutrition. The risk of hypervitaminosis is higher by using supplements. It should be kept in mind that, like drugs, supplements must also be taken correctly, and their use should be limited to specific periods of life when nutrition is deemed insufficient to meet the body’s needs. 6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Synthetic vs natural vitamins Synthetic and natural vitamins have an identical structure; however, there are major differences in the results obtained from supplementation with one or the other. In fact, vitamins interact with many other components in food. The interaction between these different elements creates a synergy that manages to obtain results that the synthetic vitamin alone cannot achieve. 7 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin classification Cristina Angeloni https://www.jaypeedigital.com/book/9789351522096/chapter/ch10 Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Water-soluble Fat-soluble Absorption Directly into the bloodstream First in the lymph, then in the blood Transport Free Many require protein transporters Storage area They circulate freely in body Trapped in fat cells fluids Excretion The excess is readily Slow excretion, they tend to eliminated by the kidneys remain in fat cells Toxicity Possibility of reaching toxic High possibility of reaching levels if taken as supplements toxic levels when taken as supplements Needs Required in frequent doses (1 Required in periodic doses to 3 per day) (even weeks or months) Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Role of B vitamins in energy metabolism The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B1 Thiamine Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Thiamine - Structure Exists in 4 forms: non-phosphorylated thiamine, thiamine monophosphate , diphosphate and triphosphate Thiazole ring Pyrimidine ring Thiamine diphosphate or thiamine pyrophosphate Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  https://lpi.oregonstate.edu/mic/vitamins/thiamin B 1 13  Content of thiamine in some foods RDA 1.1 mg / day for women, 1.2 for man The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B deficiencies 1 As the B-vitamins are involved in most energy-generating processes, the deficiency symptoms include fatigue, apathy, muscle weakness, and reduced cognitive function. Thiamin-deficiency disease is called beriberi. In this disease, the body’s inability to metabolize energy leads to muscle wasting and nerve damage; The heart muscle may also be affected, and the patient may die of heart failure. Thiamin deficiency is also seen in industrialized countries in people with chronic heavy alcohol consumption – it is generally accompanied by low thiamin intake – it reduces thiamin absorption. B 1 15 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B toxicity 1 Toxic effects over 500 mg per day for one month. Two enzymes break down thiamine – Thiaminase I, present in the intestines of some fish – Thiaminase II, produced by intestinal bacteria Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B2 Riboflavin Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  ACTIVE COENZYME FORMS of VIT B 2 : FMN FAD B 2 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Reactions in which vitamin B2 intervenes Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  https://lpi.oregonstate.edu/mic/vitamins/thiamin B 2  Functions Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  CONTENT OF RIBOFLAVIN IN CERTAIN FOODS RDA is 1.3 mg/day for men and 1.1 mg/day for women The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 B 2 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Deficincy Called ariboflavinosis is often accompanied by other nutrient deficits Clinical signs of deficiency appear after about 3–4 months of inadequate Advanced Nutrition and Human Metabolism (Sareen S. intake) Gropper, Jack L. Smith etc.) B 2 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B3 Niacin B 3 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  NIACIN - VITAMIN B3 or PP The term niacin refers to both nicotinic acid and its amide, nicotinamide, both derivatives of pyridine Coenzyme forms : NADH nicotinamide adenin dinucleotide NADPH nicotinamide adenin dinucleotide phosphate nicotinamide nicotinic acid B 3 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25 NAD+ and NADP+ synthesis from the amino acid tryptophan. Niño-Narvión et al. NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota. Nutrients. 2023 Jun 30;15(13):2992  ENDOGENOUS SYNTHESIS OF NIACINE (Vit.B 3 or PP) 60 mg tryptophan ® 1 mg of vitamin B 3. The presence of tryptophan therefore decreases the need for B 3 Since tryptophan also gives rise to serotonin, it can happen that if niacin is lacking more tryptophan is used as a precursor of the vitamin, dropping serotonin level. This explains the reason why dementia is observed in a strong deficiency of B 3 ( pellagra ) B 3 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  REDOX REACTIONS Carbohydrates Lipids Tryptophan Respiratory chain Le vitamines - données biochimiques, nutritionelles et cliniques II edition, Ed. CEIV, 1995 B 3 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  DEFICIENCY OF NIACINE B 3 Vit PP deficiency causes pellagra, or three D disease : dermatitis, diarrhea, dementia Dermatitis resembles sunburn; typical is the swollen and scarlet tongue Individuals who feed mainly on polenta (corn flour), in which the vitamin is not bioavailable, can develop pellagra Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Corn and niacin In corn, niacin is poorly bioavailable because it is covalently linked to complex carbohydrates (niacitin) There are low levels of tryptophan in corn The niacin in corn can be released by treatment with calcium hydroxide B 3 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  CONTENT OF NIACIN IN CERTAIN FOODS Niacin in foods is fairly stable; minimal losses of the vitamin result from cooking or storage. RDA is 16 mg NE/day for men and 14 mg NE/day for women The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 B 3  Vitamin B5 Pantothenic acid B 5 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  COENZYME ACTIVE FORMS OF PANTOTHENIC ACID - VITAMIN B5 Coenzyme A 4'-phospho-pantethine B Prosthetic group of the transporter protein of 5 the acyl groups (ACP), of the fatty acid synthase Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Pantothenic acid content in some foods B 5 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B6 Pyridoxine B 6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  PYRIDOXIN - VITAMIN B6 Vitamin B 6 exists in three forms: pyridoxine, pyridoxal , pyridoxamine coenzymatic forms are: pyridoxal phosphate (PLP) and pyridoxamine phosphate More than 60 pyridoxal phosphate-dependent enzymes are known, almost all of which are involved in the metabolism of amino acids B 6 The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Transamination of amino acids B 6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  VITAMIN B6 - IN THE MUSCLE Co-factor of glycogen phosphorylase Glucose-6-P B POWER 6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Methionine metabolism Vitamin B6, folate, and vitamin B12 are closely interrelated in the metabolism of methionine If these nutrients are not available, these conversion reactions cannot occur and homocysteine will accumulate in the blood. High levels of homocysteine have been associated with an increased risk for cardiovascular disease and as a measure of poor dietary intakes of vitamin B6, folate, and vitamin B12. The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FOOD SOURCES and NEEDS RDA is 1.3 mg /day for men and women The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 B 6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B7 Biotin B7 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  BIOTIN-VITAMIN B7 or H Biotin is the prosthetic group of ATP-dependent enzymes that catalyze carboxylation reactions ; it is bound to them via a lysine residue which forms an amide bond with the biotin arm B7 lysine Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B7 Present in food Biocytin Protein Lysine Biotin Essential hydrolysis B7 Peptidase Biotinidase because biocytin is not absorbable Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Biological role of biotin It is the coenzyme of 4 important carboxylases involved in gluconeogenesis , in the metabolism of propionate and branched chain amino acids, e in the synthesis of fatty acids It works by initially fixing the CO 2 molecule and subsequently transferring it to the molecule to be carboxylated ("biotin arm") B7 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Biotin in food Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Conditions predisposing to deficiency states Avidin binds biotin Pregnancy Biotinidase deficiency Holocarboxylase synthase deficiency (allows the binding of biotin to the different apocarboxylases ) Protein Lysine Biotin Peptidase Biotinidase B7 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B9 Folic acid B9 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FOLIC ACID-VITAMIN B9 The term folic acid (derived from the leaves) corresponds to pteroylglutamic acid ; pteroylglutamic acid B 9 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  ACTIVE COENZYME FORM: TETRAHYDROPHOLATE (THF) tetrahydrofolic acid (THF): the pteridine ring is reduced in positions 5,6,7,8 and the glutamic acid residues are 5 or 6 B Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  ACTIVE COENZYMATIC FORM: TETRAHYDROFOLATE ü The reaction that leads to the reduction of pteroylglutamic acid to tetrahydrofolate (THF) requires the enzyme dihydrofolate reductase , which uses NADPH as an electron donor ü vitamin C is also essential for this reaction ü There are therefore conditions in which primary vitamin C deficiencies can be accompanied by secondary THF deficiencies B 9 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Biological role of folic acid It gives rise to coenzymes with the function of transporting monocarbon groups derived from various metabolisms. Involved in the metabolism of amino acids and in the synthesis of nucleic acids: biosynthesis of DNA and RNA , methylation of homocysteine to methionine metabolism of some amino acids. B Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Interaction between nutrients: homocysteine levels are regulated by folate , B12 and B6 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Folate Folate plays a fundamental role in the synthesis of nucleic acids, therefore its deficiency causes alterations in all tissues characterized by high cell turnover Deficiency of folate and B 12 causes a form of megaloblastic anemia characterized by macrocytosis. In the bone marrow the erythroblasts, precursors of mature erythrocytes, undergo a megaloblastic transformation , that is, they cannot complete synchronously the maturation of the nucleus (which does not occur due to the lack of DNA synthesis) and that of the cytoplasm. They therefore become larger than normal. B 9 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Folate Folic acid deficiency is the most common form of avitaminosis in the world, especially in underdeveloped countries In the Western world, the most common causes of deficiency are: v diets low in folate v low absorption, due to diseases such as celiac disease , which leads to atrophy of intestinal cells, enteropathies or alcoholism v taking medications such as methotrexate and minopterin, inhibitors of the dihydrofolate enzyme used in chemotherapy Cristina Angeloni B Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FOLATE PREVENTS NEURAL TUBE DEFECTS During the period around conception, folate deficiency can cause developmental defects in the neural tube: - Anencephaly - Spina Bifida B Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Folic acid from supplements and fortified foods is more readily absorbed than folate naturally occurring in foods. This is because glutamate units typically must be removed from food folate prior to its absorption, a process that is only 50% efficient, whereas folic acid is already in the mono-glutamate form that is absorbed. In addition, some foods (such as cabbage) contain compounds that inhibit this process, thus decreasing folate bioavailability. Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B12 Cobalamine B 12 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  COBALAMIN-VIT B 12 It is the largest and most complex vitamin molecule Formed by a corrinic ring consisting of 4 pyrroles (similar to porphyrins) Dimethyl benzimidazole forms a nucleotide, the phosphate group of which binds to a substituent of the pyrrole ring In the center is a cobalt atom, which forms 4 coordination bonds with the N of the pyrroles, one bond with dimethyl benzimidazole and the other with a -CN, -CH3, -OH or 5- deoxyadenosine group B12 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Biological role of vitamin B12 It participates in the metabolism of propionic acid, which derives from the catabolism of fatty acids with odd numbers of carbon atoms or of certain amino acids. In the metabolism of methyl, and therefore intervenes in the synthesis of methionine from homocysteine and other methylated compounds. It is part of coenzymes that assist with DNA synthesis, which is necessary for the proper formation of red blood cells Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  ABSORPTION Advanced Nutrition and Human Metabolism (Sareen S. Gropper, Jack L. Smith etc.) B12 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FOOD SOURCES and NEEDS RDA is 2.4 ug /day for men and women The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 B12 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin B12 deficiency Deficit caused by decreased absorption due to decreased or lack of intrinsic factor secretion. It causes disorders of the nervous system (demyelination of the spinal cord) and megaloblastic anemia identical to that present in folate deficiency, hyperhomocysteinemia , cardio- and cerebrovascular and neurological disorders Strictly vegetarian diets can cause deficiency, in the elderly and pregnancy The deficiency occurs after long periods (even years) of non-intake because there are liver deposits Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  C vitamin Ascorbic acid C. Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin C or ascorbic acid O O HO O O O HO O HO C H HO C H CH2OH CH2OH ac. ascorbic ac. dehydroascorbic Vitamin C has a strong acidic character COOH and a strong reducing power due to the endiol group, formed by two hydroxyls linked to two carbons between which a double bond is interposed H C OH COOH Ascorbic acid is easily oxidizable HO inCtheHpresence of oxygenCandOmetals, with the formation of dehydroascorbic acid CH2OH C O H C OH Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FUNCTIONS OF VITAMIN C Cofactor in hydroxylation reactions , including: ü biosynthesis of collagen ( hydroxylation of proline and lysine) ü biosynthesis of carnitine, which involves two stages of hydroxylation ü biosynthesis of noradrenaline from dopamine, which is hydroxylated ü tyrosine catabolism ü reduction of folic acid to THF ü biosynthesis of steroid hormones ü biosynthesis of bile acids Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  Vitamin C “Recharges” Enzymes by Reducing Them Nutritional Sciences From Fundamentals to Food, 4th Edition (Michelle McGuire, Kathy A. Beerman) Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FUNCTIONS OF VITAMIN C COLLAGEN protein widely modified after synthesis One third of the proline is hydroxylated and the hydroxylisine forms stabilizing crosslinks. In the absence of vitamin C, collagen does not reach its mature form and this explains many of the symptoms of scurvy (gingival, subcutaneous or internal organ bleeding). 67 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FUNCTIONS OF VITAMIN C Neutralizes reactive oxygen species both directly and indirectly, causing the recycling of vitamin E at the lipid / water interface ( antioxidant action ) Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25... FUNCTIONS OF VITAMIN C... It favors the intestinal absorption of non-heme iron (= free iron) keeping it in the reduced Fe (II) state. For maximum effectiveness ascorbate should be ingested with iron-containing foods It inhibits the formation of nitrosamines These carcinogenic compounds are formed from nitrites and nitrates present as preservatives in food. Furthermore, the antioxidant action of vitamin C is also expressed against DNA, therefore it is believed that it has an antineoplastic action Lowers the concentration of histamine in the blood Increases the speed of healing of wounds and fractures 69 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  FOOD SOURCES and NEEDS RDA is 90 mg per day for men and 75 mg per day for women The science of nutrition, Thompson, Manore, Vaughan ed. Pears. 4 ed 2017 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  ABSORPTION Sodium-dependent vitamin C transporters SVCT1 Absorption decreases with increasing dose – Over a range of usual vitamin C intake (such as 30–150 mg/day), absorption is about 70–95%. – At intakes of about 1 g, less than 50% is absorbed and, – At intakes around 1.25 g, less than 35% is absorbed. Thus, given vitamin C absorption is saturable and dose dependent, more vitamin C is absorbed if several large (1 g) doses of the vitamin are ingested throughout the day than if the same amount is ingested as one single dose. Arienti G, The molecular basis of nutrition. IV edition. Ed. Piccin , 2016 71 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  VITAMIN C deficiency ü Scurvy is the deficiency manifestation observed after 1 or 2 months of total vitamin deprivation, which currently no longer occurs in Western populations. ü A limited intake of vitamins is much more common and can occur following hospitalization, chronic diseases, long-term drug therapies, alcohol abuse, smoking, acute illness, aging. ü In these cases the symptoms are nonspecific: loss of appetite, fatigue or weakness, delayed wound healing, decreased iron absorption Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25  SCURVY The signs and symptoms of scurvy are many: ü linked to the inability to synthesize mature collagen: petechiae, joint pain, internal bleeding ü linked to the production of catecholamines: hysteria, depression and hypochondria 73 Cristina Angeloni Nutritional Biochemistry and Nutraceutics – A.A. 2024/25