Comprehensive Study Guide on Water-Soluble Vitamins

Definition and General Characteristics of Vitamins

• Vitamins are defined as a group of organic nutrients.

• They are required in small quantities for a variety of biochemical functions.

• Generally, vitamins cannot be synthesized by the body and must therefore be supplied in the diet.

Functional Overview of Vitamins

• B-Vitamins as Coenzymes:     - They enable chemical reactions to take place in the body.     - Very little is needed because they are not used up in the process.     - Thiamin, niacin, and riboflavin are all required for reactions concerning energy release.     - Vitamin $B_6$, folate, and Vitamin $B_{12}$ are all required for reactions concerning building tissues.

• Vitamin C:     - Involved in the manufacture of collagen.     - Helps fight infections and repair wounds.     - Acts as an antioxidant.     - Increases iron absorption.

• Vitamin A:     - Maintains mucus membranes.     - Needed to see in dim light.     - Beta-carotene (a precursor) acts as an antioxidant.

• Vitamin E:     - Acts as an antioxidant.     - Reduces plaque sticking to arteries.

• Vitamin D:     - Needed to absorb and utilize calcium and phosphorus in bones, muscles, and nerves.

• Vitamin K:     - Needed to help the blood clot.

Classification of Vitamins

• Vitamins are divided based on their solubility into two categories:     - Water Soluble Vitamins:         - Non-B-Complex: Vitamin C (Ascorbic acid).         - B-Complex:             - Energy Releasing: Vitamin $B_1$ (Thiamin), Vitamin $B_2$ (Riboflavin), Vitamin $B_3$ (Niacin), Pantothenic acid, Biotin.             - Hematopoietic: Vitamin $B_{12}$, Folic acid.             - Other: Vitamin $B_6$ (Pyridoxine, Pyridoxal, Pyridoxamine).     - Lipid (Fat) Soluble Vitamins:         - Vitamin A.         - Vitamin D.         - Vitamin E.         - Vitamin K.

General Properties of Water-Soluble Vitamins

• Water-soluble vitamins (B and C) are adsorbed in the intestinal cells and delivered directly to the blood stream.

• The kidneys filter out excesses of most water-soluble vitamins and excrete them in urine.

• Key Characteristics:     - Dissolve in water.     - Generally readily excreted.     - Subject to cooking losses.     - Function as a coenzyme.     - Participate in energy metabolism.     - $50-90\%$ of B vitamins are absorbed.     - Marginal deficiency is more common than for fat-soluble vitamins.

Vitamin $B_1$ (Thiamin)

• Chemical Properties:     - Contains sulfur and a nitrogen group.     - Destroyed by alkali and heat.     - Active Coenzyme form: Thiamin pyrophosphate ($TPP$).

• Metabolic Functions:     - Part of the conversion of pyruvate to acetyl-$CoA$.     - Involved in the Citric Acid Cycle (TCA Cycle).     - Synthesis of neurotransmitters (decarboxylation).     - Role in nerve conduction (poorly defined).

• Food Sources:     - Wide variety of food: White bread, pork, hot dogs, luncheon meat, cold cereal.     - Enriched grains and whole grains.     - Thiaminase (which destroys thiamin) is found in raw fish.

• Absorption and Metabolism:     - Absorbed in the jejunum by a carrier-mediated system.     - Transported by red blood cells ($RBC$) in the blood.     - Excess is quickly excreted in the urine.

• Dietary Requirements:     - RDA for women: $1.1\,mg/day$.     - RDA for men: $1.2\,mg/day$.     - Surplus is rapidly lost in urine and is non-toxic.

• Deficiency (Beriberi and Wernicke-Korsakoff):     - Occurs where rice is the only staple.     - Dry Beriberi: Weakness, nerve degeneration, irritability, poor arm/leg coordination, loss of nerve transmission.     - Wet Beriberi: Edema, enlarged heart, heart failure.     - Wernicke-Korsakoff Syndrome: Wernicke’s encephalopathy with Korsakoff’s psychosis; associated with alcohol and drug abuse.

• Deficiency Manifestations:     - Decreased activity of pyruvate dehydrogenase and $\alpha$-ketoglutarate dehydrogenase leads to an accumulation of pyruvate and lactate, and decreased acetyl-$CoA$ and $ATP$ formation. This leads to decreased acetylcholine levels, altering Central Nervous System (CNS) activity.     - Decreased Transketolase Levels: Decreased Pentose Phosphate Pathway activity results in low levels of $NADPH$ (necessary for fatty acid synthesis). This leads to decreased myelin synthesis and peripheral neuropathy.

Vitamin $B_2$ (Riboflavin)

• Chemical Properties:     - Coenzymes: Flavin mononucleotide ($FMN$) and Flavin adenine dinucleotide ($FAD$).     - Sensitive to UV radiation (sunlight); must be stored in paper or opaque plastic containers.

• Metabolic Functions:     - Involved in oxidation-reduction (redox) reactions.     - Electron Transport Chain ($ETC$).     - Citric Acid Cycle (Succinate to Fumarate).     - Catabolism of fatty acids (beta oxidation).     - $FMN$-dependent enzymes: L-amino acid oxidase, $NADH$ dehydrogenase.     - $FAD$-dependent enzymes: Succinate dehydrogenase, Acyl-$CoA$ dehydrogenase, Xanthine oxidase, Erythrocyte glutathione reductase, Glycine cleavage system, Dihydrolipoate dehydrogenase.

• Food Sources:     - Milk and milk products, enriched grains, liver, oysters, Brewer’s yeast.

• Absorption and Metabolism:     - $HCl$ in the stomach releases riboflavin from bound forms.     - Absorption: Active or facilitated transport during low to moderate intake; passive absorption during high intake.     - Transported by a protein carrier in the blood.

• Dietary Requirements:     - RDA for women: $1.1\,mg/day$.     - RDA for men: $1.3\,mg/day$.     - Toxicity not documented.

• Deficiency (Ariboflavinosis):     - Rare except in elderly or alcoholics.     - Symptoms: Glossitis (inflamed tongue), cheilosis (fissures at corners of mouth), angular stomatitis (inflammation at sides of mouth), seborrheic dermatitis, stomatitis, eye disorders (cataracts), conjunctival congestion (earliest sign), throat and nervous system disorders.

Vitamin $B_3$ (Niacin)

• Chemical Properties:     - Known as the "pellagra preventing factor."     - Pyridine derivative (pyridine 3-carboxylic acid).     - Nicotinic acid (niacin) and nicotinamide (amide form).     - Can be synthesized from the amino acid Tryptophan: $60\,mg\,\text{Tryptophan} = 1\,mg\,\text{niacin}$.     - Coenzymes: Nicotinamide adenine dinucleotide ($NAD^{+}$) and Nicotinamide adenine dinucleotide phosphate ($NADP^{+}$).     - Heat stable with little cooking loss.

• Metabolic Functions:     - Participates in $200+$ redox reactions.     - $NAD^{+}$ is used for oxidation reactions to generate $ATP$ (e.g., Glucose to Pyruvate, Pyruvate to Lactate, Citric Acid Cycle reactions).     - $NADP^{+}$ is used for reductive biosynthesis.

• Food Sources:     - Mushrooms, enriched grains, beef, chicken, turkey, fish.

• Absorption:     - Readily absorbed from the stomach and small intestine via active transport and passive diffusion.     - Transported from the liver to tissues to be converted into coenzymes.

• Dietary Requirements:     - Adult: $15-20\,mg$.     - Children: $10-15\,mg$.     - Pregnancy and lactation require more.

• Deficiency (Pellagra):     - Characterized by the "3 Ds": Dermatitis (bright red erythema, Casal’s necklace around the neck, precipitated by sunlight), Diarrhea (mild or severe with blood/mucus), and Dementia (irritability, poor memory).     - Can result from an untreated corn-based diet, Hartnup disease, or alcoholism.

• Medicinal Use and Toxicity:     - $75-100 \times$ RDA used to treat hyperlipidemia (lowers $LDL$ and $TG$, increases $HDL$).     - Toxicity effects (at intakes > 500\,mg/day): Flushing of skin, itching, nausea, and liver damage.

Vitamin $B_5$ (Pantothenic Acid)

• Chemical Properties:     - Component of Coenzyme A ($CoA$) and Acyl Carrier Protein ($ACP$).     - Contains a thiol group that carries acyl compounds as activated thiol esters (e.g., succinyl-$CoA$, fatty acyl-$CoA$, acetyl-$CoA$).

• Functions:     - Essential for metabolism of carbohydrates, fats, and proteins.     - Component of fatty acid synthase.

• Food Sources and Needs:     - Meat, milk, mushrooms, liver, peanuts.     - Adequate Intake (AI): $5\,mg/day$.     - Deficiency is rare: "Burning foot syndrome," fatigue, sleep disturbance.

Biotin

• Chemical Properties:     - Found in free and bound (Biocytin) forms.     - Biotinidase in the small intestine releases biotin.

• Functions:     - Carboxylation reactions: Addition of $CO_2$ to substances.     - Carboxylation of acetyl-$CoA$ to form malonyl-$CoA$ (fatty acid elongation).     - Addition of $CO_2$ to pyruvate to yield oxaloacetate.     - Breakdown of leucine for energy.

• Food Sources:     - Cauliflower, egg yolk, liver, peanuts, cheese.     - Synthesized by intestinal bacteria.     - Avidin (in raw egg whites) inhibits absorption; requires > 12 raw eggs daily to cause deficiency.

• Needs:     - AI: $30\,\mu g/day$ for adults.     - No established Upper Limit ($UL$).

Vitamin $B_6$ (Pyridoxine, Pyridoxal, Pyridoxamine)

• Chemical Properties:     - Main coenzyme form: Pyridoxal phosphate ($PLP$).     - Heat and alkaline sensitive.

• Functions:     - Participates in $100+$ enzymatic reactions.     - Transamination and decarboxylation of amino acids.     - Synthesis of hemoglobin, white blood cells, and neurotransmitters (e.g., serotonin).     - Conversion of tryptophan to niacin.

• Metabolism:     - Absorbed passively.     - All forms are phosphorylated in the liver.     - Stored in the liver and muscle tissue.

• Deficiency:     - Microcytic hypochromic anemia.     - Convulsions, depression, confusion.     - Seborrheic dermatitis and peripheral nerve damage.

• Medicinal Use and Toxicity:     - High doses ($2-7\,g/day$) can cause sensory neuropathy.     - Irreversible nerve damage noted with levels > 200\,mg/day.

Folate (Folic Acid, Folacin)

• Structure: Consists of a pteridine group, para-aminobenzoic acid (PABA), and glutamic acid.

• Coenzyme Form: Tetrahydrofolic acid ($THFA$ or $THF$).

• Functions:     - DNA synthesis (transfer of single carbon units).     - Homocysteine metabolism.     - Neurotransmitter formation.

• Absorption:     - Absorbed as monoglutamate via folate conjugase.     - Stored primarily in the liver.     - Subject to enterohepatic circulation (bile).

• Deficiency:     - Megaloblastic Anemia: Red blood cells are unable to divide, remaining large and immature with nuclei.     - Neural Tube Defects: Spina bifida and anencephaly in newborns.

• Needs:     - RDA: $400\,\mu g/day$ for adults.     - Prenatal supplements often contain $800\,\mu g$.     - Excess folate can mask a Vitamin $B_{12}$ deficiency.

Vitamin $B_{12}$ (Cyanocobalamin)

• Chemical Properties: Contains cobalt. Forms include methylcobalamin and 5-deoxyadenosylcobalamin.

• Absorption Mechanism:     1. B-12 in food is released by stomach digestion.     2. Binds to R-protein (from salivary glands) in the acidic pH of the stomach.     3. Trypsin from the pancreas releases B-12 from R-protein in the intestine.     4. B-12 links with Intrinsic Factor (IF) from stomach parietal cells.     5. The B-12-IF complex is absorbed in the ileum.     6. Bound to transport protein Transcobalamin II in the blood.

• Functions:     - Folate metabolism.     - Maintenance of myelin sheaths (nerve function).     - Conversion of methylmalonyl-$CoA$ to succinyl-$CoA$ (Citric Acid Cycle).

• Food Sources: Found only in foods of animal origin (meat, seafood, eggs, milk); synthesized by bacteria.

• Deficiency:     - Pernicious Anemia: Megaloblastic anemia coupled with nerve degeneration (tingling, numbness, paralysis).     - Achlorhydria (lack of stomach acid) in the elderly can decrease absorption.     - Treatment: Monthly injections, nasal gel, or megadoses for passive diffusion.

Vitamin C (Ascorbic Acid)

• Chemical Forms: Ascorbic acid (reduced) and dehydroascorbic acid (oxidized).

• Functions:     - Collagen Synthesis: Acts as a coenzyme for hydroxylase to convert proline and lysine into hydroxyproline and hydroxylysine, creating strong connective tissue.     - Antioxidant: Water-soluble intracellular/extracellular reducing agent.     - Iron Absorption: Enhances the absorption of iron.     - Biosynthesis: Involved in making carnitine, serotonin, thyroxine, and corticosteroids.

• Food Sources: Citrus, potatoes, peppers, strawberries, spinach. Extremely sensitive to heat, oxygen, iron, and copper.

• Dietary Requirements:     - RDA Men: $90\,mg/day$.     - RDA Women: $75\,mg/day$.     - Smokers: additional $+35\,mg/day$.     - Upper Level ($UL$): $2\,g/day$.

• Deficiency (Scurvy):     - Occurs after $20-40$ days of deficiency.     - Symptoms: Fatigue, pinpoint hemorrhages, bleeding gums and joints, loss of dental cement.     - Rebound Scurvy: Occurs upon immediate halt of high-dose supplementation.