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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)
  • FunctionThis image depicts lower extremity edema in a patient with wet beriberi
    • 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 (4C)
        • 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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