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Chemistry

Metabolic

Understanding the biochemical roles of vitamins and their metabolic pathways is critical for appreciating their impact on health and disease

General Principles of Vitamin Metabolism

  • Vitamins as Essential Nutrients
    • Vitamins are organic compounds that are essential for human health but cannot be synthesized in sufficient quantities by the body
    • They must be obtained from dietary sources or supplements
  • Classification of Vitamins
    • Water-Soluble Vitamins: B vitamins (thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate, cobalamin) and vitamin C
    • Fat-Soluble Vitamins: Vitamins A, D, E, and K
  • General Metabolic Functions
    • Coenzymes: Many vitamins act as coenzymes, which are essential for the activity of enzymes involved in metabolic reactions
    • Antioxidants: Some vitamins act as antioxidants, protecting cells from damage caused by free radicals
    • Hormone-Like Functions: Some vitamins have hormone-like functions, regulating gene expression and cell differentiation
    • Other Functions: Some vitamins are involved in vision, blood clotting, and immune function
  • Absorption and Transport
    • Water-Soluble Vitamins: Absorbed directly into the bloodstream
    • Fat-Soluble Vitamins: Absorbed along with dietary fats, requiring bile acids and pancreatic enzymes
    • Transport: Vitamins are transported in the bloodstream either freely or bound to carrier proteins
  • Storage and Excretion
    • Water-Soluble Vitamins: Not stored in the body to a significant extent; excess is excreted in the urine
    • Fat-Soluble Vitamins: Stored in the liver and adipose tissue; excess can lead to toxicity
  • Deficiency and Toxicity
    • Vitamin Deficiency: Occurs when intake is inadequate, leading to impaired metabolic functions and specific deficiency symptoms
    • Vitamin Toxicity: Occurs when intake is excessive, leading to adverse effects

Water-Soluble Vitamins

Thiamin (Vitamin B1)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Conversion to Active Form: Converted to thiamin pyrophosphate (TPP) by thiamin pyrophosphokinase
  • Biochemical Actions
    • Coenzyme for Carbohydrate Metabolism: TPP is a coenzyme for several key enzymes in carbohydrate metabolism
      • Pyruvate dehydrogenase complex: Converts pyruvate to acetyl-CoA
      • α-Ketoglutarate dehydrogenase complex: Part of the citric acid cycle
      • Transketolase: Part of the pentose phosphate pathway
  • Deficiency
    • Beriberi: Characterized by neurological and cardiovascular symptoms
    • Wernicke-Korsakoff Syndrome: Neurological disorder associated with chronic alcohol abuse
  • Toxicity
    • Rare

Riboflavin (Vitamin B2)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Conversion to Active Forms: Converted to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)
  • Biochemical Actions
    • Coenzyme for Redox Reactions: FMN and FAD are coenzymes for numerous oxidoreductase enzymes involved in energy metabolism
      • Complex I and Complex II of the electron transport chain
      • Succinate dehydrogenase: Part of the citric acid cycle
      • Fatty acyl-CoA dehydrogenase: Involved in fatty acid oxidation
  • Deficiency
    • Ariboflavinosis: Characterized by cheilosis (cracking at the corners of the mouth), glossitis (inflammation of the tongue), and dermatitis
  • Toxicity
    • Rare

Niacin (Vitamin B3)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Synthesis: Can be synthesized from tryptophan, but this process is inefficient
    • Conversion to Active Forms: Converted to nicotinamide adenine dinucleotide (\(NAD^+\)) and nicotinamide adenine dinucleotide phosphate (\(NADP^+\))
  • Biochemical Actions
    • Coenzyme for Redox Reactions: NAD+ and NADP+ are coenzymes for numerous dehydrogenase enzymes involved in energy metabolism and biosynthesis
      • Glycolysis, citric acid cycle, fatty acid oxidation, and pentose phosphate pathway
  • Deficiency
    • Pellagra: Characterized by the “three Ds”: dermatitis, diarrhea, and dementia
  • Toxicity
    • Niacin Flush: Skin flushing and itching at high doses
    • Liver damage

Pantothenic Acid (Vitamin B5)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Conversion to Active Form: Used to synthesize coenzyme A (\(CoA\))
  • Biochemical Actions
    • Component of Coenzyme A (CoA): \(CoA\) is essential for numerous metabolic reactions
      • Acetyl-CoA: Involved in the citric acid cycle, fatty acid synthesis, and fatty acid oxidation
      • Acyl carrier protein (ACP): Involved in fatty acid synthesis
  • Deficiency
    • Rare due to its widespread occurrence in foods
  • Toxicity
    • Rare

Pyridoxine (Vitamin B6)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Conversion to Active Form: Converted to pyridoxal phosphate (\(PLP\))
  • Biochemical Actions
    • Coenzyme for Amino Acid Metabolism: \(PLP\) is a coenzyme for numerous enzymes involved in amino acid metabolism
      • Transaminases: Transfer amino groups between amino acids and keto acids
      • Decarboxylases: Remove carboxyl groups from amino acids to form neurotransmitters
      • Glycogen phosphorylase: Involved in glycogen breakdown
  • Deficiency
    • Neurological symptoms, dermatitis, and anemia
  • Toxicity
    • Peripheral neuropathy

Biotin (Vitamin B7)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Synthesis: Can be synthesized by intestinal bacteria
  • Biochemical Actions
    • Coenzyme for Carboxylation Reactions: Biotin is a coenzyme for several carboxylase enzymes
      • Pyruvate carboxylase: Converts pyruvate to oxaloacetate in gluconeogenesis
      • Acetyl-CoA carboxylase: Converts acetyl-CoA to malonyl-CoA in fatty acid synthesis
      • Propionyl-CoA carboxylase: Involved in the metabolism of odd-chain fatty acids and branched-chain amino acids
  • Deficiency
    • Rare, but can occur with excessive consumption of raw egg whites (contains avidin, which binds biotin)
  • Toxicity
    • Rare

Folate (Vitamin B9)

  • Metabolism
    • Absorption: Absorbed in the small intestine
    • Conversion to Active Form: Converted to tetrahydrofolate (THF) and other folate coenzymes
  • Biochemical Actions
    • Coenzyme for One-Carbon Transfer Reactions: THF is a coenzyme for numerous enzymes involved in one-carbon transfer reactions
      • DNA synthesis: Required for the synthesis of purines and pyrimidines
      • Amino acid metabolism: Involved in the interconversion of serine and glycine
  • Deficiency
    • Megaloblastic anemia, neural tube defects in developing fetuses
  • Toxicity
    • Can mask vitamin B12 deficiency

Cobalamin (Vitamin B12)

  • Metabolism
    • Absorption: Requires intrinsic factor, which is secreted by parietal cells in the stomach
    • Conversion to Active Forms: Converted to methylcobalamin and adenosylcobalamin
  • Biochemical Actions
    • Coenzyme for Two Important Enzymes
      • Methionine synthase: Converts homocysteine to methionine
      • Methylmalonyl-CoA mutase: Involved in the metabolism of odd-chain fatty acids and branched-chain amino acids
  • Deficiency
    • Pernicious anemia (due to lack of intrinsic factor), neurological symptoms
  • Toxicity
    • Rare

Ascorbic Acid (Vitamin C)

  • Metabolism
    • Absorption: Absorbed in the small intestine
  • Biochemical Actions
    • Antioxidant: Scavenges free radicals and protects against oxidative damage
    • Collagen Synthesis: Required for the hydroxylation of proline and lysine in collagen
    • Iron Absorption: Enhances the absorption of non-heme iron
    • Neurotransmitter Synthesis: Involved in the synthesis of norepinephrine
  • Deficiency
    • Scurvy: Characterized by bleeding gums, poor wound healing, and anemia
  • Toxicity
    • Gastrointestinal distress, kidney stones

Fat-Soluble Vitamins

Vitamin A

  • Metabolism
    • Absorption: Absorbed along with dietary fats
    • Transport: Transported in the bloodstream bound to retinol-binding protein (RBP)
    • Storage: Stored in the liver
  • Biochemical Actions
    • Vision: Retinal is a component of rhodopsin, the light-sensitive pigment in the retina
    • Cell Differentiation: Retinoic acid regulates gene expression and cell differentiation
    • Immune Function: Supports the immune system
  • Deficiency
    • Night blindness, xerophthalmia (dry eyes), and impaired immune function
  • Toxicity
    • Liver damage, bone abnormalities, and birth defects

Vitamin D

  • Metabolism
    • Synthesis: Can be synthesized in the skin upon exposure to sunlight
    • Activation: Requires hydroxylation in the liver and kidneys to form the active form, calcitriol (1,25-dihydroxyvitamin D)
  • Biochemical Actions
    • Calcium and Phosphate Metabolism: Calcitriol regulates calcium and phosphate absorption in the intestine, bone remodeling, and kidney reabsorption
  • Deficiency
    • Rickets (in children), osteomalacia (in adults), and osteoporosis
  • Toxicity
    • Hypercalcemia, kidney stones, and soft tissue calcification

Vitamin E

  • Metabolism
    • Absorption: Absorbed along with dietary fats
    • Transport: Transported in the bloodstream by lipoproteins
    • Storage: Stored in adipose tissue
  • Biochemical Actions
    • Antioxidant: Protects cell membranes from lipid peroxidation
  • Deficiency
    • Rare, but can occur in individuals with fat malabsorption
    • Neurological symptoms and hemolytic anemia
  • Toxicity
    • Increased risk of bleeding

Vitamin K

  • Metabolism
    • Absorption: Absorbed along with dietary fats
    • Synthesis: Can be synthesized by intestinal bacteria
  • Biochemical Actions
    • Blood Clotting: Required for the carboxylation of glutamate residues in several clotting factors (II, VII, IX, and X)
    • Bone Metabolism: Involved in bone mineralization
  • Deficiency
    • Bleeding disorders
  • Toxicity
    • Rare, but can interfere with anticoagulant medications

Summary Table of Vitamins

Vitamin Primary Function Deficiency Symptoms Toxicity Symptoms
Thiamin (B1) Carbohydrate metabolism Beriberi, Wernicke-Korsakoff syndrome Rare
Riboflavin (B2) Redox reactions Ariboflavinosis (cheilosis, glossitis, dermatitis) Rare
Niacin (B3) Redox reactions Pellagra (dermatitis, diarrhea, dementia) Niacin flush, liver damage
Pantothenic Acid (B5) Component of coenzyme A Rare Rare
Pyridoxine (B6) Amino acid metabolism Neurological symptoms, dermatitis, anemia Peripheral neuropathy
Biotin (B7) Carboxylation reactions Rare Rare
Folate (B9) One-carbon transfer reactions Megaloblastic anemia, neural tube defects Can mask vitamin B12 deficiency
Cobalamin (B12) Methionine synthase, methylmalonyl-CoA mutase Pernicious anemia, neurological symptoms Rare
Ascorbic Acid (C) Antioxidant, collagen synthesis Scurvy (bleeding gums, poor wound healing, anemia) Gastrointestinal distress, kidney stones
Vitamin A Vision, cell differentiation, immune function Night blindness, xerophthalmia, impaired immune function Liver damage, bone abnormalities, birth defects
Vitamin D Calcium and phosphate metabolism Rickets (children), osteomalacia (adults), osteoporosis Hypercalcemia, kidney stones, soft tissue calcification
Vitamin E Antioxidant Neurological symptoms, hemolytic anemia Increased risk of bleeding
Vitamin K Blood clotting, bone metabolism Bleeding disorders Rare, can interfere with anticoagulant medications

Clinical Significance

  • Nutritional Deficiencies: Vitamin deficiencies can lead to a wide range of health problems, including anemia, neurological disorders, and immune dysfunction
  • Chronic Diseases: Vitamins play a role in the prevention and management of chronic diseases, such as cardiovascular disease, cancer, and diabetes
  • Dietary Supplements: Vitamin supplements can be beneficial for individuals with inadequate dietary intake or specific health conditions, but excessive supplementation can be harmful
  • Personalized Nutrition: Understanding an individual’s vitamin status and genetic factors can help optimize dietary recommendations and supplement use

Key Terms

  • Vitamin: An organic compound that is essential for human health
  • Coenzyme: A substance that is required for the activity of an enzyme
  • Antioxidant: A substance that protects cells from damage caused by free radicals
  • Free Radical: An unstable molecule that can damage cells
  • Metabolism: The sum of all chemical reactions that occur in a living organism
  • Absorption: The process by which nutrients are taken up from the digestive tract into the bloodstream
  • Transport: The process by which nutrients are carried in the bloodstream to tissues and organs
  • Storage: The process by which nutrients are stored in the body
  • Excretion: The process by which waste products are eliminated from the body
  • Deficiency: A condition in which the body does not have enough of a particular nutrient
  • Toxicity: A condition in which the body has too much of a particular nutrient