Metal metabolism Flashcards
loop of geomicrobiology
- geosphere minerals undergo bacterial leaching of metal ions
= biosphere proteins - biosphere proteins undergo bacterial deposition of metal ions
= geosphere minerals
what metal is debatably essential
chromium
- difficult to demonstrate deficiencies because of ethics.
- haven’t found a reason that it is essential
- however it is present, suggesting that it might be
essential metals of focus
Mn
Fe
Cu
Zn
how much Zn is present in a 70kg human body
2-3g
how much Cu is present in a 70kg human body
100mg
how much Fe is present in a 70kg human body
3-5g
how much Mn is present in a 70kg human body
12-20mg
functions of metals in proteins
- catalytics; 50% enzymes require metals
- structural; tertiary, quaternary, quinary
- regulatory
what is quinary structure of proteins
different types of proteins coming together
What are the different ligands of metal in proteins
N: Hist
O: Glu, Asp
S: Cys
what does N ligand stand for
Hist
What does O ligand stand for
Glu, Asp
What does S ligand stand for
Cys
method of identifying if protein has metal-binding sites
looking at the spacing of the amino acids
example of a kown Zn proteinase
Thermolysin found in bacteria
example of a putative Zn proteinase
LTA4 hydrolase found in human)
mining sequence database
- structural genomics. search for 3D structure of metalloprotein (protein database PDB)
- determine liganvd signatures
- search for homology in sequence database
- find putative metalloprotein (curator)
what is the indirect method whih predicts the sizes of human metalloproteins
mining sequence database
what % of entire proteome is non heme Fe
1.1%
what % of entire proteome is Cu
0.3%
what % of entire proteome is Zn
10%
what % of entire protoeme is Mn
?
how do ligand interactions differ between metals
as you move down the periodic table, ionic radius increases and coordination numbr increases
= weaker ligand interactions
what is the function of Na+ and K+
they are minerals needed for nerve conductions. Need proteins to maintain electrochemical gradietnq
sodium requirements
2.3g/day
potassium requirements
4.7g/day
sodium and potassium inside cells
Na+: 12mM
K+: 140mM
sodium and potassium outside cells
Na+: 140mM
K+: 5mM
function of Mg2+
- cofactor
- enzyme complexes
e. g ATP is nearly always a magnesium complex
what is ATP nearly always a complex of
Magnesium complex
Essentail trace metals
Mn Fe Co Cu Zn Mo
when is Ni essential
good bacteria in the gut need Ni
what is Mo
molybdenum
- only 4 enzymes in humans with Mo
- pterin cofactor binds Mo
Use of Co
- only 2 enzymes in humans (methylmalonyl-CoA, methionine synthase)
- Is the centre of vitamin B12 structure
- vitamin B12 = cobalamin
Uses of Mn
- Mn deficiency is uncommon
- too much Mn causes Manganism = Parkinson’s
- total number of Mn enzymes is unknown (mitochondiral superoxide, dismutase, arginase, pyruvate decarboxylase)
Uses of Ni
only 9 enzymes, but none have been identified in the human body.
Good bacteria found in the gut need Ni
Cu uses
- deficiency causes Menkes disease = fatal
- overload causes Wilson’s disease = treatable with chelating agen of Zn supplementation
- dozens of human Cu enzymes (superoxide dismutuase, cytochrome C oxidase)
- mostly found as Cu+ because intracellular environment is highly reducing
- metallochaperones prevent free radicals being formed
cuprous
Cu+
cupric
Cu2+
what prevent formation of free radicals
metallochaperones
what controls mammalian intracellular copper homeostasis
- tightly controlled by transporters and metallochaperons
uses of Fe
- redox active which gives most of its functions:
- 250 non-heme proteins
- oxgen transport and activation
- many proteins
- overload and deficiency can occur
ferrous
Fe2+ = active iron
ferric
Fe3+ = storage iron
what is the state of active iron
Fe2+, ferrous
what is the state of storage iron
Fe3+, ferric
how is Fe2+ found
- in Fe/S clusters
- bound to heme
- non-heme Fe; mononuclear and dinuclear
examples of heme iron proteins
- hemoglobin
- myoglobin
- cytochomes
- peroxidase
- catalase
- heme-binding proteins (sensors and transporters)
when does iron redox recycling occur
aerobic iron metabolism
process of iron redox recycling
- iron is outside of enterocyte in intestine as Fe3+
- Dcytb on membrane reduces iron to Fe2+
- Fe2+ transported across membrane via DMT1
- most of iron stored in cell as Ferritin
- remaining exported as Fe2+ via Fpn
- Fe2+ is oxidised again outside cell by Hp
- Fe3+ binds to Tf for transportation in blood
Tf
transferrin = transport protein
Ft
ferritin = storage protein
DMT1
divalent metal transporter 1
Dcyt b
duodenal cytochrome b
Hp
hephaestin
Fpn
ferroportin
what is ferritin
- complex proteon with an iron mineral core, where iron is storoed as on oxide
- iron oxidase acitivity
- once iron has been oxidised, it migrates to the core for storage, hence iron core
what is transferrin
- uses Fe3+
- binds two Fe3+ from intestine cell and transport to blood where needed
- has two biding sites
- transferrin uptake by cells is by receptor mediated endocytosis
transferrin receptor
- two irons bind to receptor
- pit forms an endosome to enter cell
- endosome is acidified to release iron into cell
- protein recyled to surface, both Tf and Tf receptor
what happens to iron during cyctochrome P450 reaction cycle
goes to very high oxidation state: Fe5+
inborn errors of Cu metabolism
Deficiency: copper deficiency, Menkes disease
Overload: copper toxicity, Wilson’s disease
inborn erros of Fe metabolism
deficiency: iron deficiency
overload: iron toxicty, primary iron overload disorders: hemchromatosis (HFE1-4), aceruloplasminemia, atransferrinemia, hemosiderosis
inborn errors of Zn metabolism
deficiency: acrodermatitis enteropathica
overload: zinc ‘toxicity’
Which one of the following elements is believed to be non-essential
aluminium
