Minerals Flashcards
Definition of mineral
Naturally occurring inorganic substance
Definition of manganism
A form of Parkinsonism caused by Mn overload. Reversible in early stages, irreversible in later stages due to ZnT10 transporter mutation.
Definition of reticuloendothelial macrophages
Have ability to phagocytose bacteria, viruses, foreign substances and worn out cells
Definition of primary haemochromatosis
Caused by genetic defect, that controls how much iron you absorb
Definition of secondary hemochromatosis
Result of another disease or condition that causes iron overload
Chelating agents
Chemical compounds that react with metal ions to form stable, water soluble complex
Nutritionally essential chemical elements
Na K Mg Ca Mo Mn Fe Co Cu Zn
Describe the shape of the dose/response curve: essential substance
Low dose, deficient
Adequate dose, adequate
Overdose, overload, toxic
Elements in biological tissues
10-3mg/g
K
Ca
Na
Mg
Elements in biological tissues
10-6 ug/g
Zn Fe Cu Sr* Se
Elements in biological tissues
10-9 ng/g
Rb* Mn As* Ba* Ni* Co Hg* Mo Cs* Cd*
Elements in biological tissue
10-12 pg/g
Cr
U*
Pb*
What are the 4 essential minerals
Na
Mg
K
Ca
Concs of Na, K inside and outside the cell and requirements and function
Na, inside cells (mM) 12 Na, outside cell (mM) 140 Requirement (g/d) 2.3
K, inside cells (mM) 140 K, outside cell (mM) 5 Requirement (g/d) 4.7
Major function nerve conduction
Mg2+ function
Cofactor complex (ATP) Enzyme complexes
Ca2+ function
Signalling in cells
Essential trace metals
Mn Fe Mo Co Cu Zn
Amounts of each trace element
- Mn
- Fe
- Cu
- Zn
Mn 12-20mg
Fe 3.7g
Cu 100mg
Zn 2.3g
Uses of cobalt (Co)
In cobalamin (B12)
2 enzymes only in humans
Total 1mg, 2ug/d for adults
Uses of molybdenum (Mo)
Molybdenum cofactor 4 enzymes only -sulfite -xanthine -aldehyde oxidases -mitochondrial amidoxime reducing component (mARC)
Uses of manganese
Used in many many enzymes such as
- mitochondrial superoxidase dismutase
- Arginase
- glutamine synthase
- pyruvate carboxylase
Toxicity of manganese
Mn2+ relatively toxic
Overload leads to manganese (form of Parkinsonism)
Daily values of Fe, Cu, Zn
Fe 18mg
Cu 2mg
Zn 15mg
3 functions of metals in proteins
Catalysis
Structure
Regulation
Ligand donors of amino acids in metalloproteins
Only some proteins can bind to metal ions
If they have N (his)
If they have O (glu, asp, tyr)
If they have S (cys, met)
Distribution of Fe in the body
Dietary Fe absorbed in the duodenum (makes up 10% of all absorbed Fe)
Plasma transferin => myoglobin and bone marrow for formation of RBC and liver for storage
Reticuloendothelial macrophages degrade RBCs, reload transferin
Loss in sloughed mucosal cells, desquamation, blood loss.
Hepcidin controls iron metabolism
Fe uptake in intestinal cell
Fe III reduced to Fe II by duodenal cytochrome b
Divalent metal transporter I transports Fe II into intestinal cell.
Fe II can either be stored in ferritin or it can be transported out of the cell with ferroportin
Hephaestin reduces Fe II on the basal side of the cell to FeIII
Fe III can bind to transferin and be carried in the blood
Fe storage
Feroxidase core
4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2H2O
When it needs to be stored, oxidized to Fe III
When it needs to be released, reduced to Fe II
Iron uptake with receptor mediated endocytosis
Fe II, transferin binds to transferin receptor in clathrin coated pit
Forms an endosome with divalent metal transporter
Proton pump acidifies endosome, Fe dissociates from transferrin and exits via divalent metal transporters
Apo-Tf and transferin receptor return to cell surface, endosome breaks down
Fe either stored as ferritin or enters mitochondria
If in ferritin, can form hemosiderin or the formation of nonerythroid cells
Genetic diseases and Fe metabolism
Primary iron overload disorder (haemochromatosis type 1)
Treated with phlebotomy
Juvenile/HFE2, HFE3, HFE4
Aceruloplasminemia, atransferrinemia
Chelating agents for iron overload
Deferoxamine to treat secondary iron overload, removes excess Fe
Differences between Fe and Zn
Red
>90% in haem
Redox active Fe2+/Fe3+
Clinical tests
Colourless
Diluted among many proteins
Redox inert Zn2+
No clinical test
Uses of zinc in proteins
Carbonic anhydrase, alcohol dehydrogenase
Many proteins (Zn insulin complex, NT in brain)
All enzymes,e families
Recognition of DNA/RNA, lipids, gene expression
Cellular Zn homeostasis
No of proteins that are associated with Zn and their function
ZIP, zinc import, 14 proteins
ZNT, zinc export, 10 proteins
MT, metallothiones (zinc transport, > 10 proteins)
MTF1-zinc sensor
Zn total amount and requirements
Total amount 2-3g
Daily requirement 2-3mg
Human zinc deficiency reasons
Lack of Zn in nutrition
Parasites
Fe deficient
Genetic
Signs of Zn deficiency
Suppressed cell mediated immunity Dermatitis Poor wound healing Alopecia Growth retardation Delayed sexual maturation Impaired CNS, PNS Taste, vision, smell affected Appetite loss Dwarfism
Genetic basis for Zn deficiency
-2 pathologies
Aerodermatitis enteropathica
- severe skin lesions, death from infections
- completely curable with Zn
- Mutation in ZIP4, uptake low
Transient neonatal zinc deficiency
- affects child, does not obtain enough Zn from mother
- curable when Zn given to child
- Mutation in Zn T2
Uses of copper (Cu) in proteins
Ceruloplasmin, ferroxidase
Superoxide dismutase , 2O2 + 2H+ => H2O2 + O2
Cytochrome C oxidase, terminal electron acceptor for O2
Lysol oxidase, collagen crosslinking
Tyrosinase, melanin production
Dopamine B hydroxyls, catecholamine synthesis
Basically involved in hormone and energy metabolism
Genetic diseases, copper accumulation
Treatment for copper accumulation
Wilson’s disease
In liver, toxicity, hepatolenticular degeneration
Overflow of Cu => brain (mental deterioration)
Kayser Fleischer rings
Chelation therapy w D-penicillamine, treat Cu overload
Genetic diseases, copper deficiency
Treatment for copper deficiency
Defective absorption of Cu in intestines
Hair depigmentation, steely, kinky
Deterioration of NS
No cure in infants
Cellular Cu homeostasis
How is Cu taken up into the cell and processed
Cu II reduced to Cu I and taken up by Cu transporter I
Specific chaperones will transport Cu I to where it is needed in the cell (mitochondria)
ATPases export Cu
