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Updated: Mar 2 2023

Water Soluble Vitamins

Images
https://upload.medbullets.com/topic/102072/images/vitamin.jpg
  • Overview
    • Examples
      • B1 (thiamine: TPP)
      • B2 (riboflavin: FAD and FMN)
      • B3 (niacin: NAD+)
      • B5 (pantothenic acid: CoA)
      • B6 (pyridoxine: PLP)
      • B12 (cobalamin)
      • C (ascorbic acid)
      • biotin
      • folate
    • Characteristics
      • when consumed in excess are eliminated in the urine
        • exceptions are B12 and folate (stored in liver)
      • B-complex deficiencies often result in dermatitis, glossitis, diarrhea
  • Vitamin B1 (Thiamine)
    • Function
      • a cofactor for several enzymes such as thiamine pyrophosphate (TPP)
        • pyruvate dehydrogenase (glycolysis)
        • α-ketoglutarate dehydrogenase (TCA cycle)
        • transketolase (HMP shunt)
        • branched-chain AA dehydrogenase (metabolism of Val, Leu, Ile)
    • Deficiency
      • causes
        • alcoholism
          • most common cause in US
          • EtOH interferes with thiamine absorption in small intestine
        • malnutrition
          • non-enriched rice
      • symptoms
        • impaired glucose breakdown due to decreased activity of pyruvate dehydrogenase
          • leads to ATP depletion
          • highly aerobic tissues are affected first
        • Wernicke's syndrome
          • ataxia, confusion, nystagmus, ophthalmoplegia
        • Korsakoff's syndrome
          • confabulation, psychosis, and mammillary body hemorrhage
        • beriberi
          • dry beriberi
            • peripheral neuropathy due to demyelination
            • symmetrical muscle wasting
            • no fluid retention
          • wet beriberi
            • high-output cardiac failure (dilated cardiomyopathy)
            • edema
        • diagnosis
          • can be made by measuring increased transketolase activity after thiamine administration
            • mechanism
              • thiamine is a cofactor necessary for the function of transketolase
          • diagnosis of thiamine deficiency is made by history
        • management
          • patients that present with thiamine deficienty should be treated with thiamine first
            • after thiamine has been administered, can then administer glucose in IV fluids
              • mechanism
                • thiamine is a cofactor for enzymatic steps in glycolysis
                • administering glucose before thiamine could further decrease thiamine levels for enzymes like transketolase which could exacerbate Wernicke-Korsakoff syndrome
  • Vitamin B2 (Riboflavin)
    • Function
      • cofactor for
        • oxidation and reduction (e.g., FADH2)
        • succinate dehydrogenase
      • precursor to FAD and FMN
      • involved with many dehydrogenase enzymes
    • Deficiency
      • causes
        • severe malnourishment
      • symptoms
        • cheilosis (inflammation of the lips and scaling and fissures at the corners of the mouth)
        • corneal vascularization
        • dry skin
        • magenta-colored tongue
  • Vitamin B3 (Niacin)
    • Function
      • constituent of NAD+and NADP+ (used in redox reactions)
      • derived from tryptophan
      • involved with many dehydrogenase enzymes
      • synthesis requires vitamin B2 and B6
    • Deficiency
      • causes
        • diets low in tryptophan or niacin
          • corn staple diets
        • Hartnup disease
          • ↓ tryptophan absorption in kidneys and small intestine
        • malignant carcinoid syndrome
          • ↑ tryptophan metabolism in production of serotonin
        • INH therapy
          • ↓ vitamin B6 leading to ↓ niacin synthesis
      • symptoms
        • glossitis
        • severe deficiency leads to pellagra (3 D's)
          • diarrhea, dermatitis, dementia
    • Excess
      • causes
        • nicotinic acid given at high doses as hyperlipidemic treatment (raised HDL)
      • symptoms
        • facial flushing
          • mediated by prostaglandins, treated with aspirin
        • intrahepatic cholestasis
        • hyperglycemia
        • hyperuricemia
  • Vitamin B5 (Pantothenate)
    • Function
      • component of coenzyme A required for many enzymatic processes
        • fatty acid synthase (fatty acid metabolism)
        • acyl transferases
        • pyruvate dehydrogenase (PDH)
        • α-ketoglutarate dehydrogenase (TCA cycle)
    • Deficiency
      • rare
      • symptoms
        • dermatitis, enteritis, alopecia, and adrenal insufficiency
  • Vitamin B6 (Pyridoxine)
    • Function
      • converted to pyridoxal phosphate, a cofactor used in
        • transamination (e.g., ALT and AST in protein catabolism)
        • decarboxylation reactions
        • glycogen phosphorylase
        • cystathionine synthesis
        • heme synthesis
      • required for the synthesis of niacin from tryptophan
    • Deficiency
      • causes
        • INH (isoniazid)
        • oral contraceptives
        • goat milk
        • chronic alcoholism
      • symptoms
        • convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias, cheilosis or stomatitis
  • Vitamin B12 (Cobalamin)
    • Function
      • cofactor for homocysteine methyltransferase
        • transfers CH3 groups as methylcobalamin
        • cofactor for homocysteine + N-methyl THF → methionine + THF
      • cofactor for methylmalonyl-CoA mutase
        • metabolism of propionate (odd-chain fatty acid degradation) at the conversion of methylmalonyl CoA → succinyl CoA
        • folate not directly involved in this pathway
        • megaloblastic anemia with an elevated methylmalonyl CoA indicates B12 deficiency as opposed to folate
      • metabolism of Val, Met, ILe, Thr
    • Source
      • found only in animal products
      • several years of reserves stored primarily in the liver
    • Deficiency
      • causes
        • pernicious anemia
          • intrinsic factor required for absorption in the terminal ileum
          • B12 not absorbed when intrinsic factor not produced from the parietal cells of the stomach
        • gastric bypass surgery
          • less intrinsic factor produced
        • resection of terminal ileum
          • e.g., Crohn's disease
        • malabsorption
          • sprue, enteritis
        • bacterial overgrowth of terminal ileum
        • diphyllobothrium latum (parasite)
          • competes for B12 absoroption
        • vegan diets
        • use Schilling test to detect etiology of the deficiency
          • differential process of radiolabeled B12
            1. oral B12 + IM B12
            2. B12 + intrinsic factor
            3. B12 + antibiotics
            4. B12 + pancreatic enzymes
      • symptoms
        • macrocytic, megaloblastic anemia
          • found also in folate deficiencies
        • hypersegmented PMNs
        • neurologic symptoms due to abnormal myelin
          • paresthesias and subacute combined degeneration
            • dorsal columns of spinal cord degenerate causing loss of proprioception and vibration sensation
          • not found in folate deficiencies
          • could be reversible with administration of B12
            • severe symptoms and longer term B12 deficiency = more residual neurologic damage and less function regained
  • Folic Acid
    • Function
      • converted to tetrahydrofolate (THF), a coenzyme for 1-carbon transfer/methylation reactions
      • important for the synthesis of nitrogenous bases in DNA and RNA (thymidylate synthase)
        • recall: uridine + methyl group = thymidine
    • Deficiency
      • most common vitamin deficiency in the United States
      • absorbed in the jejunum via the action of intestinal conjugase
      • causes
        • dietary deficiency
          • elderly
          • goat milk
        • seen in alcoholism and pregnancy
          • liver stores last three months
        • deficiency can be caused by several drugs
          • e.g. phenytoin, sulfonamides, methotrexate, EtOH
      • findings
        • macrocytic, megaloblastic anemia
        • hypersegmented neutrophils
        • homocysteinemia
          • ↑ risk of DVT and atherosclerosis
        • no neurologic symptoms + normal methylmalonic acid level (as opposed to vitamin B12 deficiency)
        • deficiency in pregnancy causes fetal neural tube defects
          • supplemental folic acid in early pregnancy reduces risk
  • Biotin
    • Function
      • cofactor for carboxylation enzymes (adds a 1-carbon group)
        • pyruvate carboxylase
          • pyruvate (3C) → oxaloacetate (4C)
          • gluconeogenesis
        • acetyl-CoA carboxylase
          • acetyl-CoA (2C) → malonyl-CoA (3C)
          • fatty acid synthesis
        • propionyl-CoA carboxylase
          • propionyl-CoA (3C) → methylmalonyl-CoA (4C)
          • odd-carbon fatty acids, Val, Met, Ile, Thr catabolism
    • Deficiency
      • relatively rare
      • causes
        • antibiotic use
        • excessive ingestion of raw eggs
          • contains avidin which binds biotin
      • symptoms
        • dermatitis, alopecia, enteritis, lactic acidosis
  • Vitamin C (Ascorbic Acid)
    • Function
      • antioxidant
        • regenerates vitamin E
        • ↓ oxidation of LDL
      • keeps iron in Fe2+ reduced state
        • ↑ intestinal absorption
      • collagen synthesis
        • essential for hydroxylation of proline and lysine
        • prolyl and lysyl hydroxylases
        • addition of hydroxyl group allows for hydrogen bonding between fibers
        • without cross-linking triple helix shape cannot form
      • synthesis of norepinephrine
        • necessary for dopamine β-hydroxylase
          • converts dopamine to NE
      • hepatic synthesis of bile acids
      • keeps THF in reduced form
      • protects against nitrosylation of amides
        • occurs in the stomach with presence of food preservatives
        • nitrosamines/amides are carcinogenic
    • Source
      • found in fruits and vegetables
      • British sailors carried limes to prevent scurvy
    • Deficiency
      • causes
        • diet lacking citrus fruits and green vegetables
        • infants on formula that is boiled too long
          • excessive heat destroys vitamin C
        • cigarette smoking
      • symptoms
        • scurvy
          • swollen gums, bruising, perifollicular hemorrhage, poor wound healing, glossitis, ↑ bleeding time
          • anemia due to combined iron and folate deficiency
        • infantile scurvy
          • 2-10 months
          • excessively boiling formula
    • Excess
      • symptoms
        • formation of renal calculi made from calcium oxalate (vitamin excreted as oxalate)
        • diarrhea, nausea, vomiting
        • excess iron absorption in those predisposed (hemochromatosis, repeat blood transfusions)
  • S-Adenosylmethionine (SAM)
    • Not a vitamin but an important cofactor
    • Synthesis
      • ATP + methionine → SAM
      • regeneration of methionine (and thus SAM) is dependent on vitamin B12 and folate
    • Function
      • SAM transfers methyl units
        • similar to THF
      • SAM is required for the conversion of NE to epinephrine
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