Selenium

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Selenium
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HISTORY

• 1817 Discovered by Berzelius
• 1930 As a toxic trace element
• 1957 Prevent hepatic necrosis in
  vitamin E deficient rats
• 1958 Se deficiency in muscular
  dystrophia in farm animal
• 1959 Se in immune system
• 1973 Biochemical function
• 1979 Se deficiency in TPN and Keshan
  disease

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Biochemistry

• Se is an essential element , constituent of GPX
  defend against oxidant stress and toxicity of
  heavy metal, metabolism of TH ,reproduction
  system
• Organic form se-c , se-m,se-methyl-se-c ,
  se-methyl-se-m
• Inorganic formselenide,selenite ,selenate
• Selenomethionine
• Se-M can,t synthesis , from diet ,Met for pr
  synthesis.
• Selenocysteine
• Analogue of cys , 21aa in DNA , present in se-prs
  
• Active biological form
• Selenoproteins
• GPX(4 type) ,IDI(3isoform) ,Thioredoxin reductase
  (3isoform) ,Mitochondrial capsule se-pr,
  Selenoprotein P , Selenoprotein W, Prostate
  epithelial Selenoprotein(15kDa)

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• 
  
  ribosome
• Serine tRNA seryl-tRNA
  se cys - tRNA
  tRNA
  
  se
  
• 
  
  growth pp growth pp
• 
  
  
  chain of GPX chain of
  GPX
• Se-Cys structure
  Hse CH2 CHCOOH
• 
  
  NH2
• Se-Met structure
  CH3 Se
  CH2CH2CHCOOH
• 
  
  NH2

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Forms of se In diet

Forms of se In tissue A Se-cyc

Inorg.selenium

se-cys in
GPX ,se-pr-p, Other form

Excretion Se-Met

se-Met in proteins

se-Cys in GPX
,se-pr-p,
other
se-pr
Excretion
central selenium metabolic pool
se-Met in free methionine pool
central selenium metabolic pool
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Selenoproteins
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GPX
ACTIVITY

• 4 subunit(cell,plasma,GI,pl hydroproxide)
• Se-def decreases GPX activity
• Function
• Prevent the peroxidation of membrane ox
  damage
• Antioxidant reduction of HPs(H2O2
  ,sterol,steroid,PG, FFA,Pr ,NA)
• Free radical scavenger
• Immune response mechanism
• As a storage Pr
• Synthesis of arachidonic acid metabolites

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• HOOH
  2H2O
• 2GSH
  GSSG
• ROOH
  H2OROH
• 2GSH
  GSSG
• GSHRº GS º RH
• 2GS º GSSG
  2GSH
• 
  2NADPH NADP

GPX
GPX
GPX
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Selenium Metabolism

• Absorption
• duodenum
• se-M , M Active
  
• se-C unknown
• Inorganic form passive
• Absorption gt 80 from food
• Se-M gtse-C
• Transport
• little known
• Bound to plasma pr (Alb in mice , ß lipoprotein
  in human )
• Se pr-p as a transport protein

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Selenium Metabolism

• Excretion
• Urine principal route
• Faces unabsorbed se
• Breath high intake
• Homeostasis
• Regulation of excretion via urine

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Daily dietary intake whole blood values of se

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Dietary source

• organic meats sea food 0.4-1.5
  µg/g
• Muscle meats
  0.1-0.4 µg/g
• Cereal grain
  lt0.1-0.8lt µg/g
• Fruit vegetable
  lt0.1 µg/g
• Dairy products
  lt0.1-0.3 µg/g
• Human milk
  10-30 µg/l
• Cow,s milk
  5-10 µg/l

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Recommended dietary intakes of se for adults
(µg/d)
Dietary intake
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Recommended dietary intakes of se
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Recommended dietary intakes of se
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Selenium deficiency

• Keshan disease
• Kashin beck disease
• TPN
• Cardiovascular disease
• Viral infection
• Cancer
• Thyroid disease
• Reproduction male , female
• Mood
• others PEM , Hemolytic anemia,Systic fibrosis
  ,Coelia disease ,aging Broncho Pulmonary
  dysplasia, uremia, RA, asthma,pancreatitis,

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Keshan Disease

• Endemic Cardiomyopathy
• Children and women of child bearing age
• area of china (from northeast to southwest)
• Etiology se-def ,environmental toxins ,viral
  infection ,seasonal
• Clinicaldizziness ,malaise , loss of appetite ,
  nause , chilly sensation , HF , arrhythmia ,
  Cardiogenic shock
• Laboratory S se ,GPX activity ,hair se decrease

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Kashin -Beck disease

• Endemic osteoarthropathy
• Children (5-13Y)
• Geographic distribution like keshan disease
• Etiology unknown ,se-def

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Selenium toxicity

• in animal daily intake gt0.44ppm
• Teratogenic effect is seen in offspring of
  animal in seleniferus area
• is not a human Teratogenic
• Clinical featuredietary intake gt900 µg/d
• Acute se toxicity nausea ,vomiting,hair
  loss,nail change ,irritability,fatigue,
  peripheral neuropathy
• Severe toxicity dietary intake gt3.2-6.7 mg/d
• Chronic selenosis loss of hair nail , skin
  lesion ,tooth decay , nervous system
  abnormalities

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Occurrence ,virulence ,disease progression of
some viral infection Coxackie isolated from
Keshan disease Se is a crucial nutrient for HIV
Protect the person with hepatitis virus B/C
against the progression to liver cancerVirus
hijack the se of host incorporates into viral
se-pr reduces the ability of of host ,s
effective immune responseseveral virus
(molluscum contiagiosum , HIV, coxackie , )have
GPX homologus and protect the virus from host
cell-derivied peroxides
se and viral infection
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Immune dysfunction loss of CD4_increase IL4,6,10
decreaseIL2,IFN _opportunistic infection _
increase tumors _decrease T.C,proliferation ,
responseto mitogen Ag Se is an antioxidant and
immunomodulator Sensitive marker of progression
Independent predictor of mortality in adult and
children Se-supplement 1.up regulate
IL2increased activation , proliferation
,differentiation programmed cell death of
Th-cells 2.down regulate abnormally high
level of IL 8(neurological damage, viral
replication), TNF (kaposi,s sarcoma ,wasting
syndrome)

SELENIUM AND HIV
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Effect of se on the immune cell function
Se supplementation

• In vivo
• Increase Neutrophil migration and super
  oxide anion activity(cow)
• High affinity IL2 receptor (mouse)
• T-cell proliferation and function following
  age related decline (mouse)
• Natural killer cell activity (mouse and
  human)
• Cytotoxic T-cell activity (mouse)
• T-cell response to pokeweed mitogen (cow)
• Lymphokine activated killer cell activity
• Vaccine-induced immunity to malaria(mice)
• Decrease
• Erythema following UV exposure(mouse and
  human)
• UV-induced skin cancers and mortality
  (mouse)

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In vitro Decrease HIV replication in
T-cells(human) Cell death following UV
irradiation of skin cells(mouse and human )
DNA damage and lipid peroxidation in UV-exposed
skin cells (mouse And human )
Cell death following paraquat exposure
(human) Apoptosis induced by UV in normal
skin cells (human) Increase Antibody
response (primary and secondary ) to virus (cow)
Apoptosis in tumors (mouse and human )
Killing by macrophage(human)
Phytohaemagluttinin response in lymphocytes
(human)

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increasePlatelet aggregation and leukotriene
synthesis(atopic human )Virulence of
Coxsackievirus (mouse)CD4 T-cells
decreaseIgG and IgM titers(human)Ab
production by lymphocyte (mouse)Neutrophil
chemotaxis(goat)Neutrophil and leukocyte
activity(pig)Candidacidal activity by
neutrophils (rat)CD8 Tcells ,CD4-/CD8-
thymocytes (mouse)
SE deficiency