questions 10

Water Soluble Vitamins

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Topic updated on 11/07/17 9:11am

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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Qbank (3 Questions)

TAG
(M1.BC.5) A homeless woman presents with shortness of breath on exertion and pedal edema. Cardiac workup performed shows evidence of dilated cardiomyopathy and increased cardiac output. She also has decreased sensation over both extremities bilaterally. Which vitamin deficiency most likely caused these symptoms? Topic Review Topic

1. Vitamin C
2. Vitamin B1
3. Vitamin B3
4. Vitamin B6
5. Vitamin A

PREFERRED RESPONSE ▶
TAG
(M1.BC.12) A 62 year old woman presents to her doctor complaining of painful tingling and burning in her feet for the past year. Careful physical exam demonstrates that she has poor position sense in her bilateral lower extremities. Lab results reveal elevated urine and plasma methylmalonic acid concentrations. What vitamin deficiency is this woman most likely suffering from? Topic Review Topic

1. Vitamin C
2. Vitamin B1
3. Vitamin B12
4. Biotin
5. Folic acid

PREFERRED RESPONSE ▶
TAG
(M1.BC.75) A 59-year-old female presents to your office with complaints of progressive numbness and tingling in her fingers and toes over the last several months. She also reports "feeling weak" in her arms and legs. The patient's past medical history is significant for hypertension and Crohn's disease, which has been well-controlled since undergoing an ileocolectomy 7 years ago. Physical examination is significant for the following findings: decreased sensation to light touch, temperature, and vibration in the bilateral lower extremities; ataxia; positive Romberg sign. Deficiency of which of the following is most likely responsible for this patient's symptoms? Topic Review Topic

1. Vitamin B1
2. Vitamin B2
3. Vitamin B3
4. Vitamin B6
5. Vitamin B12

PREFERRED RESPONSE ▶
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