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Water Soluble Vitamins Overview

• Water-soluble vitamins include Vitamin B and Vitamin C
• Vitamin B contains different forms such as B1, B2, B3, B5, B6, B7, B9, and B12
• B1, B2, B3, B5, B7 release energy
• B9 and B12 are hematopoetic

Vitamin B1: Thiamine

Thiamine Structure

• Thiamine is composed of a substituted pyrimidine and thiazole ring linked by a methylene bridge.
• Pyrophosphate moiety is donated by ATP, catalyzed by thiamine pyrophosphate kinase enzyme
• The active form of thiamin is thiamin pyrophosphate (TPP)
• TPP serves as a coenzyme in several metabolic pathways.

Thiamine: Requirements and Sources

• 90% of thiamine present in animal tissues is phosphorylated, which becomes TPP
• Thiamine in plants isn't phosphorylated
• A dietary requirement of thiamine is related to energy metabolism and depends on caloric intake
• Rich sources include yeast, yeast extract, bran from cereal, oatmeal, whole-grain cereals, pulses, nuts, hearts, pork loin, kidney and liver.
• Moderate sources include beef, lamb, chicken, eggs, fruits and vegetables
• Poor sources include polished rice, milk, and white flour

Thiamine Absorption

• Absorbed from the jejunum and proximal ileum
• There are 2 absorption mechanisms
• Above 5mg/day uses an active, ATP-dependent absorption
• Below 5mg/day uses passive diffusion
• Converted to thiamine pyrophosphate (TPP) in enterocytes and released as thiamine
• Transported to tissue bound to albumin and is converted to TPP after cellular uptake

Thiamine Function

• TPP is a coenzyme for oxidative-decarboxylation including:
• Pyruvate dehydrogenase
• α-ketoglutarate dehydrogenase
• Transketolase reactions uses thiamine as a coenzyme
• Generates ribose sugars, supplies NADPH utilized for redox and biosynthetic reactions
• Thiamine derivative is used in the metabolism of branched-chain amino acids
• Maple syrup disease can be treated with large doses of thiamine
• Thiamine trisphosphate is another thiamine derivative involved in nerve conduction
• Required for acetylcholine synthesis and the ion translocation of neural tissue.

Thiamine Deficiency

• Malnutrition can cause thiamine deficiency
• Deficiency is likely occur in areas where polished rice is the major component of the diet
• A diet high in thiaminase-rich food such as raw freshwater fish, raw shellfish, and ferns, can cause thiamine deficiency
• Foods high in anti-thiamine factors such as tea, coffee, and nuts, cause thiamine deficiency
• Continuous alcohol consumption (ethanol reduces the active transport of thiamine) causes thiamine deficiency
• Usage of tobacco, or carbonate and citrate food additives can impair thiamine absorption.
• Beriberi can occur as a result of thiamine deficiency
• Beriberi is characterized by poor appetite, peripheral neuropathy, fatigue, constipation, muscle spasms, or muscle weakness
• Neuromuscular symptoms are predominant symptoms of Dry beriberi
• Wet beriberi manifests as neurological and cardiovascular symptoms along with edema
• Cerebral beriberi (Wernicke-Korsakoff Syndrome) is characterized by apathy, loss of memory, and a rhythmical to-and-fro motion of the eyeballs
• Chronic alcoholism may result in beriberi because of poor diet or issues with intestinal absorption
• Tachycardia, anorexia, and vomiting as symptoms of infantile beriberi are due to low thiamine in breast milk.

Thiamine: RDA (Recommended Daily Allowance)

• Thiamine requirements depend on energy metabolism, and is associated with caloric intake
• 0.4mg/1000 calories is the general recommendation

Thiamine stability

• Thiamine is liable to heat in neutral or alkaline medium therefore it can degrade during cooking
• It maintains stability in acidic medium, and is safe up to 100°C

Thiamine Status Assessment

• Diagnosing a Vitamin B₁ deficiency can be done by measuring transketolase levels in erythrocytes
• Measuring urinary thiamine, plasma pyruvate, or plasma lactate levels can evaluate thiamin status particularly after an glucose load
• Determination of erythrocyte transketolase activity alongside TPP serves as a coenzyme, confirms the deficiency

Thiamine Toxicity

• Toxicity is rare

Vitamin B2: Riboflavin

Riboflavin Structure

• Riboflavin has a three-ring structure that contains isoalloxazine linked to ribitol moiety
• Riboflavin is characterized as a yellow compound

Riboflavin: Requirements and Sources

• Rich in milk, milk products, liver from meat & eggs
• Moderate in vegetables & fruits
• Poor in cereals

Riboflavin Absorption

• Ingested as flavoproteins
• FAD & FMN elements that release protein complex in the stomach & release riboflavin in the intestine
• Absorbed through active ATP-dependent transport in the small intestine
• Activation of riboflavin is ATP dependent via a specific enzyme

Riboflavin Functions

• Converted to active forms of Flavin-Mononucleotide (FMN) and Flavin-Adenine Dinucleotide (FAD), which act as co-enzymes
• About 150 oxidation-reduction reactions use FMN and FAD that relate to the follows
• Metabolism of carbohydrates, proteins, and fats
• Activation of Vitamin B12 and folate
• Protection of erythrocytes, or protection of cells from oxidative stress.
• Examples of functions of riboflavin include reactions with D-amino acid oxidase, succinate dehydrogenase, acyl CoA dehydrogenase, glycerol 3-phosphate dehydrogenase, xanthine oxidase, and pyruvate dehydrogenase
• During oxidation, FAD/FMN receives two hydrogen atoms to reduce to FADH2/FMNH2

Riboflavin Deficiency

• Rare since the dietary requirement is low and the intestinal flora synthesizes it
• General disorder- Avitaminosis
• Usually combined with other deficiencies like beriberi, pellagra, and kwashiorkor
• Symptoms of riboflavin deficiency:
• Angular stomatitis (mouth inflammation)
• Cheilosis (cracks/fissures at lips)
• Glossitis (smooth, purplish tongue)
• Dermatitis
• Vascularization of cornea

Riboflavin: Required Daily Amount and Stability

• 1.3-1.6 mg/day is recommended
• Stability: unstable to light in both acidic and basic conditions
• Under acidic conditions, light yields lumichrome
• Under alkaline conditions, sunlight yields lumiflavin
• Light yields inactive forms of B2
• Transitory riboflavin deficiency may arise during phototherapy for infant physiological jaundice.

Riboflavin: Diagnostic Testing

• Riboflavin presence found via serum riboflavin, which in turn may be found by measuring the erythrocytes’ glutathione reductase levels.

Vitamin B3: Niacin

Niacin Structure

• Refers to both nicotinic acid and nicotinamide
• Known as Pellagra preventing factor
• Niacinamide is a form present in tissues
• Derivatives of pyridine, chemically related to nicotine but functionally different

Niacin: Requirements and Sources

• Liver, poultry, legumes, milk, and eggs
• Found in yeast extract
• Cereals are bound from it
• Obtained from tryptophan metabolism that requires Vitamin B6.
• 60mg of Tryptophan equates to 1mg of niacin.
• Bacteria in the gut synthesize it (inefficient).

Niacin: Active Form

• Is nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+)

Niacin Function

• Co-enzyme in oxidation-reduction reactions for dehydrogenase or reductase enzymes.
• Supports oxidative catabolic reactions like NAD+/NADH-TCA and Glycolysis
• Aids in reductive anabolic reactions such as NADP+/NADPH-HMP, and Cholesterol FA synthesis
• Crucial for DNA repair including cellular responses from DNA damage

Niacin Deficiency

• Pellagra is brought on through disorder in skin, GIT and CNS
• Symptoms of Pellagra are Dermatitis (scaly), Diarrhea, Dementia and Death (3 D's)
• Pellagra is typically seen in populations that consume sorghum/maize. Pellagra develops because Maize contains the following:
• Low levels of tryptophan
• Presence of Trp analogs
• Niacin bound in ester form (niacytin)
• Sorghum contains an inhibitors of key enzymes and high content of leucine
• Hartnup Disease cannot absorb or transport trp
• Vitamin B6 deficiency acts as an coenzyme in niacin synthesis from tryptophan

Niacin Therapeutic Uses and Properties

• Nicotinic Acid intake not in amide form produces a high niacin level
• Vasodilation is enabled via high niacin level
• VLDL synthesis and secretion is inhibited
• Lowers serum triglyceride/lipoprotein production including LDL variants
• Enables serum HDL

Niacin Toxicity and RDA

• Intake of nicotinic acid in doses 3-4x of the recommended can cause a "niacin flush", which dilates capillaries and causes fatty liver.
• RDA: 13-20mg per day

Vitamin B5: Pantothenic Acid

• Pantoic acid and Beta Alanine constitutes this acid
• Coenzyme-A(CoA-SH) - 80%
• Acyl carrier protein - Phosphopantetheine & phosphopantethenate

Sources of Pantothenic Acid

• Egg, liver, yeast extract, wheat germs, cereals
• Food sources of the acid include Egg, liver, cereals, yeast, and it's widely distributed
• No RDA has been established

Pantothenic Acid Functional Overview

• Part of Coenzyme A that assists the TCA cycle reactions
• Essential to cholesterol synthesis with a Formation of Sterols (Cholesterol and 7-Dehydrocholesterol).
• Oxidation and Formation of Fatty acids (ACP).
• Aids Utilization of Keto acids

Pantothenic Acid Deficiency

• Rare due to the acids presence
• A sign that does occur it includes Paresthesia (sensation of tingling, pricking, or numbness of a person's skin).

Vitamin B6: Pyridoxin

B6 Structure

• Pyridoxine is derived through pyridoxal, pyridoxine, pyridoxamine
• Can be interconverted.
• pyridoxal phosphate (PLP) is its active form
• Heat-stable, but decomposes in light or alkaline solutions.

B6 Source

• Meat, fish, poultry are major
• Dairy and grains are poor
• pyridoxine is mainly in plants
• pyridoxamine & pyridoxal present in animals

B6 Absorption

• Involves passive diffusion.
• Phosphorylated pyridoxine vitamers are hydrolyzed for intestinal membrane alkaline phosphatase. The dephosphorylated forms are then absorbed
• FMN-dependent oxidase enzyme converts pyridoxine phosphte and pyridoxamine phosphate to PLP
• PLP is major form circulating
• Storage of pyridoxine occur with the enzyme glycogen phosphorylase in skeletal muscle when acting as a coenzyme.

B6 Function in the Body

• High in brain, liver and muscle.
• Assists as a coenzyme for the enzymes like transaminases & decarboxylases.
• Can also aid Kynureninase, Cystathionine a-synthase, Cystathionine gamma-lyase and ALA synthase.

B6 Deficiency/Recommendations

• Creates hypochromic microcytic anemia and Glossitis
• Scaly dermatitis, Numbness, Tingling, Irritability, Convulsive seizures
• Tuberculous patients on antituberculosis drug in structure with Isoniazid suffer from B6 deficiency and must be given large doses of B6
• RDA: 1.3 mg/day in adults, Upper limit: 100 mg/day

Vitamin B7: Biotin

• Composed of sulfur contents two fused rings with an imidazole
• Sources from yolk, organ meats like Liver, Kidney, Milk. Also found in legumes and nuts.
• Required to synthesize biotin
• Exists as itself as a coenzyme form
• Assists carboxylation fixation of CO2

B7 Deficiency

• Biotin is required to avoid Glycoprotein and Avidin from damaging egg with B7 properties
• Rare to acquire, however, symptoms can results in depression, experimental anorexia, dermatitis, animals will often show insomnia and or muscle pain

Vitamin B9: Folic Acid

Folate (B9) Structure

• pteridine is attached to para amino benzoic acid (PABA) with glutamic acids
• Tetrahydrofolate (THF) is active form

Folate Absorption

• Folate is naturally polyglutamate and becomes monoglutamate
• Folate is absorbed and delivered to cells through the small-intestines
• Vitamin b12 assists in making coenzymes for DNA synthesis.

Folate Function

• Tetrahydrofolate acts as coenzyme and metabolizes for Leucopoieses, Erythropoiesis, and DNA/RNA Nucleic Acid composition

Folate deficiency overview

• Megaloblastic Anemia, and Neural Tube Defects
• Women require 400 micrograms of folic acid daily
• Mask Vitamin B12 deficiencies

Vitamin B12 (Cobalamine) Overview

• Highly complex and mostly synthesized by microorganisms
• Source is animal foods
• B12 in food is bound to the protein
• releases it to combine with intrinsic to have small intestine absorb factor
• Then transformed and stored as methycobalamine for cell production
• Normal amount of folate and synthesis of red blood cells that ensure normal conditions of the body

B12 Functions

• Aids normal amounts as well as the syntheses of blood cells
• Creates sheaths that support nerves

B12 Deficiency/Recs

• A lack of may cause in Anemia and Pernicious disease
• May occur with the absorption of Hydrochloric or through gastrisits with Vegetarian diets
• 3 µg/day adults, 4 µg/day when lactating