Selenium Flashcards
(100 cards)
1
Q
Selenium is an…
A
Essential trace element
2
Q
Primary function of Se
A
Incorporation into selenoproteins (25)
3
Q
Inorganic selenium is found in…
A
Soil
4
Q
Selenite
A
SeO32
(Inorganic)
5
Q
Selenous acid
A
H2SeO3
(Inorganic)
6
Q
Selenate
A
SeO42
(Inorganic)
7
Q
Organic selenium is found in…
A
Plants & animals
8
Q
Describe formation of organoselenium compounds (i.e. SeCys, SeMet)
A
Plants/microorganisms replace sulfur with selenium in the biosynthetic pathways for cysteine and methionine (sulfur-containing amino acids)
9
Q
Selenoamino acids are defined as…
A
Se covalently bonded with carbon atoms (i.e. SeMet, SeCys)
10
Q
Selenomethionine (SeMet) synthesis
A
Synthesized by plants/microorganisms
11
Q
Selenocysteine (SeCys) synthesis?
A
Co-translationally synthesized in animals/humans
Inorganic selenide is activated and added in a co-translational conversion of serene –> SeCys while the AA is bound to a specific tRNA coding for the selenoprotein
12
Q
Methionine =
A
Essential amino acid in humans/animals (diet only)
13
Q
Cysteine =
A
Synthesized from methionine
14
Q
Selenium RDA is…
A
Adults: 55 mcg/day
Infants: 15 mcg/day up to 20 mcg/day after 6 mos (based on breast milk)
Children: 20-40 mcg/day
Pregnancy: 60 mcg/day Lactation: 70 mcg/day
Selenium intakes of most Americans exceed the RDA
15
Q
Selenium RDA mostly based on…
A
Maximal expression of glutathione peroxidase 3
16
Q
What determines selenium content of plant-based foods?
A
Varies according to soil Se levels, which are affected by:
Soil pH
Organic matter in dirt
Form of selenium present
17
Q
Se content of foods tends to correlate with…
A
Protein content; because SeCys and SeMet are mostly incorporated into proteins
18
Q
Muscle meats contain…
A
0.3 to 0.5 mg Se/kg (fresh weight)
19
Q
Organ meats contain __x higher/lower concentrations of Se
A
4x to 15x higher
20
Q
Foods high in selenium
A
Brazil nuts, fish, organ meats, muscle meats, high protein foods
21
Q
Absorption of inorganic Se from food is __% (selenite)
A
84%
22
Q
Absorption of organic Se from food is __% for SeMet
A
98%
23
Q
Inorganic Se (selenate/selenite) absorbed via…
A
Diffusion
24
Q
Selenoaminoacids absorbed via…
A
Transport by amino acid transporters
25
Bioavailability of selenoamino acids from plants/animals depends on...
Digestibility of these proteins
26
Fate of ingested SeMet
Incorporated into body proteins non-specifically in place of methionine based on protein methionine content
Metabolized to selenide via same pathway which converts Met to Cys
27
Fate of ingested SeCys
Incorporate selenium indirectly as SeCys as residues in new selenoproteins
28
Fate of ingested inorganic Se (selenite or selanate)
Se incorporated as SeCys residues in new selenoproteins)
29
Describe the circulating plasma pool of Se
1. SepP1 and GPX3 (contain ~50-60% of total plasma Se)
2. Non-specific SeMet in albumin & other plasma proteins
3. A small amount of selenosugars
30
Plasma Se taken up by the liver and re-enters circulation as...
Selenoprotein P (SepP) for distribution of Se to extrahepatic tissues
31
General function of selenoproteins (3)
1. Cellular protection from oxidative stress
2. Thyroid hormone metabolism
3. Reproduction
Much more!
32
Maximal plasma selenoprotein levels occurs at...
Se intakes yielding plasma levels \> 70 ng/mL
33
List selenoproteins (4):
Glutathione peroxidases (GPX) Thioredoxin reductase Selenoprotein P Selenoprotein W
34
GPX
Glutathione peroxidase
Antioxidant enzymes that reduce ROS (e.g H2O2) by coupling their reaction with the oxidation of reduced glutathione
6 isoforms in animals
GPX activity depends on selenium status; used as a biomarker
35
Thioredoxin reductase
Regenerates several antioxidants, including Vit C
36
Selenoprotein P
Antioxidant Found in plasma and endothelial cells Transport protein for Se
37
Selenoprotein W
Found in muscle Thought to play a role in muscle metabolism
38
Se excretion
Poorly digested Se-containing proteins and insoluble Se compounds will pass through the intestinal lumen and be excreted in feces
Digested/absorbed Se excreted via the kidney, mostly as selenosugars
39
Short-term selenium intake measured in:
Blood and urine selenium concentration
40
Long-term selenium intake measured in:
Hair/nail selenium status
41
T/F: Neither SeCys from the diet nor SeCys formed in the body during SeMet catabolism or muscle catabolism can be used directly for the incorporation of SeCys into selenoproteins
True
42
Ox/Redox general principle
OILRIG
Oxidation is loss
Reduction is Gain
43
Glutathione function
Major participant in cellular antioxidant systems
Can detoxify both soluble and lipid peroxides in cytoplasm, nuclei, and mitochondria (dominant soluble antioxidant in these compartments)
Oxidation (loss of one electron) easily accommodated by sulfur
44
Describe glutathione oxidation cycle
45
Desribe glutathione peroxidase-mediated reaction
2(GSH) + H2O2 --\> GSSG + H2O
GSH is oxidized to GSSG
46
Describe glutathione reductase-mediated reaction
GSSG + NADPH+H --\> GSH + NADP
GSSG is reduced to GSH
47
GSH
Reduced glutathione
48
What is GSSG?
Oxidized glutathione
49
Enzymatic activity of glutathione reductase is dependant on what cofactor?
Riboflavin (FAD)
50
Draw glutathione oxidation cycle
51
How does selenium work with vitamin E?
One or more SeCys residues in redox-active selenoproteins work to regenerates vit E
Combined deprivation of Vit E and Se yields increased free radical attack on PUFAs
52
Draw antioxidant network in general terms
53
GPX1
Highly specific for GSH as the donor of reducing equivalents
54
GPX2
Found primarily in GI cells and liver
55
GPX3
Found in plasma & extracellular fluids
56
GPX4
Associated with cell membranes
Detoxifies H2O2s which impair membrane function & is important for sperm production
Knocking out GPX4 is embryonically lethal
57
Iodothyronine 5’-Deiodinases
Selenoprotein enzyme that converts T4 --\> T3
Selenium deficiency results in elevated levels of thyroid hormone thyroxine (T4) w/low active thyroid hormone (T3)
58
Diseases associated with selenium deficiency (2)
Keshan disease
Kashin-Beck disease
59
Keshan Disease
Cardiomyopathy mainly affecting children and young women residing in regions of China/Russia where soil Se and subsuquent dietary Se intake is very low
Acute or chronic cardiac insufficiency
Cardiac enlargement
Arrhythmias
EKG abnormalities
Largely eliminated through selenium supplementation •
May be caused by cardiophilic RNA viruses
Selenium deficiency may exacerbate RNA attack through increased viral mutation
60
Kashin-Beck Disease
Ostearthropathy affecting the epiphyseal growth plates and articular cartilage
Enlarged joints (especially of the fingers, toes and knees)
Shortened fingers, toes, and extremities
Sometimes dwarfism
Iodine deficiency, fungal toxins, & impaired thyroid hormone metabolism may be involved
A meta analysis of 15 clinical trials suggested some beneficial effect of Se supplementation
61
Symptoms of acute selenotoxicity
Severe GI symptoms, neurological symptoms, & acute cardiac/respiratory/renal failure
Due to accidental overexposure (to gram quantities of Se) to high-Se compounds such as anti-dandruff shampoo
62
Symptoms of chronic selenosis
Hair loss, nail changes, skin sensitivity
63
FDA “no observed adverse effect level”
0.8 mg/day
64
Se TUL
0.4 mg/day
65
Selenium and cancer
Anti-tumorigenic effects of Se supp noted in animal studies
Epi studies observed lower cancer incidence with higher selenium status
Nutritional Prevention of Cancer (NPC) Trial found no effect of selenium on skin cancer, yet found a decrease in overall cancer mortality, total cancer incidence, and incidence of lung, colorectal and prostate cancers (6 years)
SELECT Prostate Cancer Prevention Trial found no effect on the incidence of prostate cancer over 5-yr intervention
Effects may only be observed in those with low Se levels at baseline
66
# (Reversed)
SeO32- (I)
Selenite
67
# (Reversed)
H2SeO3 (I)
Selenous acid
68
# (Reversed)
SeO42- (I)
Selenate
69
# (Reversed)
Adults: 55 mcg/day Infants: 15 mcg/day up to 20 mcg/day after 6 mos (based on breast milk) Children: 20-40 mcg/day Pregnancy: 60 mcg/day Lactation: 70 mcg/day Selenium intakes of most Americans exceed the RDA
Selenium RDA is...
70
# (Reversed)
0.3 to 0.5 mg Se/kg (fresh weight)
Muscle meats contain...
71
# (Reversed)
4x to 15x higher
Organ meats contain \_\_x higher/lower concentrations of Se
72
# (Reversed)
84%
Absorption of inorganic Se from food is \_\_% (selenite)
73
# (Reversed)
98%
Absorption of organic Se from food is \_\_% for SeMet
74
# (Reversed)
Diffusion
Inorganic Se (selenate/selenite) absorbed via...
75
# (Reversed)
Transport by amino acid transporters
Selenoaminoacids absorbed via...
76
# (Reversed)
Digestibility of these proteins
Bioavailability of selenoamino acids from plants/animals depends on...
77
# (Reversed)
incorporated into body proteins non-specifically in place of methionine based on protein methionine content Metabolized to selenide via same pathway which converts Met to Cys
Fate of ingested SeMet
78
# (Reversed)
Incorporate selenium indirectly as SeCys as residues in new selenoproteins
Fate of ingested SeCys
79
# (Reversed)
Se incorporated as SeCys residues in new selenoproteins)
Fate of ingested inorganic Se (selenite or selanate)
80
# (Reversed)
Glutathione peroxidases (GPX) Thioredoxin reductase Selenoprotein P Selenoprotein W
List selenoproteins (4):
81
# (Reversed)
Glutathione peroxidase
Antioxidant enzymes that reduce ROS (e.g H2O2) by coupling their reaction with the oxidation of reduced glutathione
6 isoforms in animals
GPX activity depends on selenium status; used as a biomarker
GPX
82
# (Reversed)
Regenerates several antioxidants, including Vit C
Thioredoxin reductase
83
# (Reversed)
Antioxidant Found in plasma and endothelial cells Transport protein for Se
Selenoprotein P
84
# (Reversed)
Found in muscle Thought to play a role in muscle metabolism
Selenoprotein W
85
# (Reversed)
Poorly digested Se-containing proteins and insoluble Se compounds will pass through the intestinal lumen and be excreted in feces Digested/absorbed Se excreted via the kidney, mostly as selenosugars
Se excretion
86
# (Reversed)
Blood and urine selenium concentration
Short-term selenium intake measured in:
87
# (Reversed)
Hair/nail selenium status
Long-term selenium intake measured in:
88
# (Reversed)
Reduced glutathione
GSH
89
# (Reversed)
Oxidized glutathione
What is GSSG?
90
# (Reversed)
Highly specific for GSH as the donor of reducing equivalents
GPX1
91
# (Reversed)
Found primarily in GI cells and liver
GPX2
92
# (Reversed)
Found in plasma & extracellular fluids
GPX3
93
# (Reversed)
Associated with cell membranes
Detoxifies H2O2s which impair membrane function & is important for sperm production
Knocking out GPX4 is embryonically lethal
GPX4
94
# (Reversed)
Selenoprotein enzyme that converts T4 --\> T3
Selenium deficiency results in elevated levels of thyroid hormone thyroxine (T4) w/low active thyroid hormone (T3)
Iodothyronine 5’-Deiodinases
95
# (Reversed)
Cardiomyopathy mainly affecting children and young women residing in regions of China/Russia where soil Se and subsuquent dietary Se intake is very low
Acute or chronic cardiac insufficiency
Cardiac enlargement
Arrhythmias
EKG abnormalities
Largely eliminated through selenium supplementation •
May be caused by cardiophilic RNA viruses
Selenium deficiency may exacerbate RNA attack through increased viral mutation
Keshan Disease
96
# (Reversed)
Ostearthropathy affecting the epiphyseal growth plates and articular cartilage
Enlarged joints (especially of the fingers, toes and knees)
Shortened fingers, toes, and extremities
Sometimes dwarfism
Iodine deficiency, fungal toxins, & impaired thyroid hormone metabolism may be involved
A meta analysis of 15 clinical trials suggested some beneficial effect of Se supplementation
Kashin-Beck Disease
97
# (Reversed)
Severe GI symptoms, neurological symptoms, & acute cardiac/respiratory/renal failure
Due to accidental overexposure (to gram quantities of Se) to high-Se compounds such as anti-dandruff shampoo
Symptoms of acute selenotoxicity
98
# (Reversed)
Hair loss, nail changes, skin sensitivity
Symptoms of chronic selenosis
99
# (Reversed)
0.8 mg/day
FDA “no observed adverse effect level”
100
# (Reversed)
0.4 mg/day
Se TUL
