Biochemistry - nutrition

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jknell
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Biochemistry - nutrition
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2013-03-24 18:58:16
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Biochemistry - Nutrition
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  1. Vitamins
    fat soluble
    • A, D, E, K
    • Absorption dependent on gut (ileum) and pancreas
    • Toxicity is more common due to accumulation in fat
    • **Malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake causes fat-soluble vitamin deficiencies
  2. Vitamins
    water soluble
    • B1: thiamine (TPP)
    • B2: riboflavin (FAD, FMN)
    • B3: niacin (NAD+)
    • B5: pantothemic acid (CoA)
    • B6: pyridoxine (PLP)
    • B7: biotin
    • B9: folate
    • B12: cobalamin
    • C: ascorbic acid
    • **all wash out easily from the body except B12 and folate (stored in liver)
    • B-complex deficiencies often result in dermatitis, glossitis, and diarrhea
  3. Vitamin A (retinol)
    function, deficiency, excess
    • Function:
    • -Antioxidant
    • -Constituient of visual pigments (retinal)
    • -Essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells)
    • -Prevents squamous metaplasia
    • -Used to treat measles and AML, subtype M3

    *Retinol is vitamin A, so think retin-A (used topically for wrinkles and acne)

    Source: liver and leafy vegetables

    • Deficiency:
    • -Night blindness
    • -Dry skin

    • Excess:
    • -Arthralgias
    • -Fatigue
    • -Headaches
    • -Skin changes
    • -Sore throat
    • -Alopecia
    • -Teratogenic (cleft palate, cardiac abnormalities)
    • *negative pregnancy test + birth control pills are needed before isotretinoin is prescribed for severe acne
  4. Vitamin B1 (thiamine)
    function, deficiency
    • Function:
    • -Thiamine is used in thiamine pyrophosphate (TPP) which is a cofactor for several enzymes in decarboxylation reactions:
    • ↦ Pyruvate dehydrogenase (links glycolysis to TCA cycle)
    • ↦ α-ketoglutarate dehydrogenase (TCA cycle)
    • ↦ Transketolase (HMP shunt)
    • ↦ Branched-chain amino acid dehydrogenase
    • **α-ketoglutarate DH, Transketolase, and Pyruvate DH are required for ATP synthesis

    • Deficiency:
    • -Impaired glucose breakdown → ATP depletion worsened by glucose infusion
    • -High aerobic tissues (brain and heart) are affected first
    • -Wernicke-Korsakoff syndrome and beriberi
    • -Seen in malnutrition as well as alcoholism (2° to malnutrition and malabsorption)
  5. Wernicke-Korsakoff
    • B1 deficiency
    • Confusion
    • Opthalmoplegia
    • Ataxia
    • Confabulation
    • personality change
    • memory loss (permanent)
    • *Damage to medial dorsal nucleus of thalamus, mammillary bodies
  6. Beriberi
    Dry vs wet
    *Ber1Ber1 to remember vitamin B1

    • Dry beriberi:
    • - polyneuritis
    • - symmetrical muscle wasting

    • Wet beriberi:
    • -high-output cardiac failure (dilated cardiomyopathy)
    • -edema
  7. Vitamin B2 (riboflavin)
    Function, deficiency
    • Function:
    • -Cofactor in oxidation and reduction (e.g., FADH2)
    • FAD and FMN are derived from riboFlavin (B2 = 2 ATP)

    • Deficiency:
    • -Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
    • -Corneal vascularization
    • **The 2 C's of B2
  8. Vitamin B3 (niacin)
    Function, deficiency, excess
    • Function:
    • -Constituent of NAD+, NADP+ (used in redox reactions)
    • -Derived from tryptophan
    • -Synthesis requires vitamin B6
    • *NAD derived from Niacin (B33 ATP)

    • Deficiency:
    • -Glossitis
    • -Severe deficiency leads to pellegra, which can be caused by Hartnup disease (↓ tryptophan absorption), malignant carcinoid syndrome (↑ tryptophan metabolism, and INH (↓ vitamin B6)

    • Sx of pellegra:
    • -Diarrhea
    • -Dementia
    • -Dermatitis
    • *3D's of B3

    • Excess
    • -Facial flushing (due to pharmacologic doses for treatment of hyperlipidemia
  9. Vitamin B5 (pantothenate)
    Function, deficiency
    B5 is "pento"thenate

    • Function:
    • -Essential component of CoA (a cofactor for acyl transfer) and fatty acid synthase

    • Deficiency:
    • -Dermatitis
    • -Enteritis
    • -Alopecia
    • -Adrenal insufficiency
  10. Vitamin B6 (pyridoxine)
    Function, deficiency
    • FUnction:
    • -Converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation reactions, glycogen phosphorylase
    • -Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine and GABA

    • Deficiency:
    • -Convulsions
    • -Hyperirritability
    • -Peripheral neuropathy (deficiency inducible by INH and oral contraceptives)
    • -sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
  11. Vitamin B7 (biotin)
    Function, deficiency
    • Function:
    • -Cofactor for carboxylation enzymes (which add a 1-carbon group):
    • ☉ Pyruvate carboxylase: pyruvate (3C) → oxaloacetate (4C)
    • ☉ Acetyl-CoA carboxylase: acetyl-CoA (2C) → malonyl-CoA (3C)
    • ☉ Propionyl-CoA carboxylase: propionyl-CoA (3C) → methylmalonyl-CoA (4C)

    • Deficiency: relatively rare
    • -Dermatitis
    • -Alopecia
    • -enteritis
    • -Cuased by antibiotic use or excessive ingestion of raw egg

    **"Avidin in egg whites avidly binds biotin"
  12. Vitamin B9 (folic acid)
    Function, deficiency
    • Source:
    • -Found in leafy green vegetables
    • *Folate from Foliage
    • -Small reserve pool stored primarily in the liver

    • Function:
    • -Converted to tetrahydrofolate (THF); a coenzyme for 1-carbon transfer/methylation reactions
    • -Important for the synthesis of nitrogenous bases in DNA and RNA

    • Deficiency:
    • -Macrocytic, megaloblastic anemia
    • -No neurologic symptoms (as opposed to vitamin B12 deficiency)
    • -Most common vitamin deficiency in the US
    • -Seen in alcoholism and pregnancy
    • -Deficiency can be caused by several drugs (e.g., phenytoin, sulfonamides, MTX)
    • -Supplemental folic acid in early pregnancy reduces neural tube defects
  13. Vitamin B12 (cobalamin)
    Source, function, deficiency
    • Source:
    • -Found in animal products
    • -Synthesized only by microorganisms
    • -Very large reserve pool (several years) stored primarily in the liver

    • Function:
    • -Cofactor for homocysteine methyltransferase (transfers CH3 group as methylcobalamin) and methylmalonyl-CoA mutase

    • Deficiency:
    • Causes: usually by malabsorption (sprue, enteretis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's disease)
    • -Macrocytic, megaloblastic anemia
    • -hypersegmented PMNs
    • -Neurologic symptoms  (paresthesias, subacute combined degeneration) due to abnormal myelin
    • -Prolonged deficiency leads to irreversible nervous system damage

    • Dx:
    • -Schilling test to detect the etiology of the deficiency
    • B12 deficiency:
    • -macrocytic, megaloblastic anemia
    • -
  14. S-adenosyl-methionine
    • ATP + methionine → SAM
    • SAM transfers methyl units
    • Regeneration of methionine (and thus SAM) is dependent on vitamin B12 and folate
    • **SAM the methyl donor man
    • Required for the conversion of NE to epinephrine
  15. Vitamin C (ascorbic acid)
    Function, deficiency, excess
    • Source: 
    • -Found in fruits and vegetables

    • Function:
    • -Antioxidant
    • -Also facilitates iron absorption by keeping iron in Fe2+ reduced state **Pronounce "absorbic" acid
    • -Necessary for hydroxylation of proline and lysine in collagen synthesis
    • -Necessary for dopamine β-hydroxylase, which converts dopamine to NE

    • DeficiencyScruvy:
    • -Swollen gums
    • -Bruising
    • -Hemarthrosis
    • -Anemia
    • -Poor wound healing
    • -Weakened immune response
    • **Vitamin C deficiency causes sCurvy due to a Collagen synthesis defect

    • Excess:
    • -Nausea, vomiting, diarrhea
    • -fatigue, sleep problems
    • -Can increase risk of iron toxicity in predisposed individuals (transfusions, hereditary hemochromatosis)
  16. Vitamin D
    • D2 = ergocalciferol: ingested from plants
    • D3 = cholecalciferol: consumed in milk, formed in sun-exposed skin
    • 25-OH D3 = storage form
    • 1,25-(OH)2 D3 (calcitriol) = active form
  17. Vitamin D
    Function, deficiency, excess
    • Function:
    • - ↑ intestinal absorption of calcium and phosphate

    - ↑ bone mineralization

    • Deficiency:
    • -Rickets in children: bone pain and deformities)
    • -Osteomalacia in adults (bone pain and muscle weakness)
    • -hypocalcemic tetany
    • -Breast milk has ↓ vitamin D (supplement in dark-skinned patients)

    • Excess:
    • -hypercalcemia
    • -hypercalciuria
    • -loss of appetite
    • -stupor
    • -Seen in sarcoidosis (↑ activation of vitamin D by epithelioid macrophages)
  18. Vitamin E
    Function, deficiency
    • Function:
    • -Antioxidant (protects erythrocytes and membranes from free-radical damage)
    • **E is for Erythrocytes

    • Deficiency:
    • -↑ fragility of erythrocytes (hemolytic anemia)
    • -Muscle weakness
    • -Posterior column and spinocerebellar tract demyelination
  19. Vitamin K
    Function, deficiency
    • Function:
    • -Catalyzes γ-carboxylation of glutamic acid residues on various proteins concerned with blood clotting
    • -Synthesized by intestinal flora
    • **K is for Koagulation
    • -Needed for synthesis of clotting factors II, VII, IX, X, and proteins C and S
    • -Warfarin: Vitamin K antagonist

    • Deficiency:
    • -Neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K
    • -Can also occur after prolonged use of broad-spectrum antibiotics
    • -Not in breast milk; neonates are given vitamin K injection at birth to prevent hemorrhage
  20. Zinc
    Function, deficiency
    • Function:
    • -Essential for activity of 100+ enzymes
    • -important in the formation of zinc fingers (transcription factor motif)

    • Deficiency:
    • -Delayed wound healing
    • -hypogonadism
    • -↓ adult hair (axillary, facial, pubic)
    • -dysgeusia
    • -anosmia
    • -May predispose to alcoholic cirrhosis
  21. Ethanol metabolism
    • NAD+ is the limiting reagent
    • Alcohol dehydrogenase operates via zero-order kinetics
  22. Fomepizole
    Inhibits alcohol dehydrogenase and is an antidoe for methanol or ethylene glycol posoning
  23. Disulfiram (Antabuse)
    Inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms)
  24. Ethanol hypoglycemia
    • Ethanol metabolism increases NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate
    • -Inhibits gluconeogenesis and stimulates fatty acid synthesis
    • → hypoglycemia and hepatic fatty change (hepatocellular steatosis) seen in chronic alcoholics
    • Overproduction of lactate → acidosis
    • Depletion of oxaloacetate shuts down the TCA cycle, sthunting acetyl-CoA into ketone production
    • Breakdown of excess malate ↑ NADPH and thus fatty acid synthesis
  25. Malnutrition
    Kwashiorkor
    • Protein malnutrition
    • Presentation:
    • -skin lesions
    • -edema
    • -liver malfunction (fatty change due to decreased apolipoprotein synthesis)
    • -Small child with swollen belly

    • **MEAL:
    • Malnutrition
    • Edema
    • Anemia
    • Liver (fatty)
  26. Malnutrition
    Marasmus
    • Energy malnutrition
    • Presentation:
    • -tissue and muscle wasting
    • -loss of subcutaneous fat
    • -variable edema

    **Marasmus results in Muscle wasting

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