MetalsMetals

Metals essential for life:

The role for most is uncertain

Na, K, Mg, Ca

V, Cr, Mn, Fe Co, Ni, Cu, Zn

Mo, W

General roles of metal ions in biologyNa, K:Na, K: Charge carriers

Osmotic and electrochemical gradients

Nerve function

Mg, Ca:Mg, Ca: Enzyme activators

Structure promoters

Lewis acids

Mg2+: chlorophyll, photosynthesis

Ca2+: insoluble phosphates

Other metal ions: less well defined and Other metal ions: less well defined and more more

obscure rolesobscure roles

Zn:Zn: Metalloenzymes

Structure promoters

Lewis acid

Not a redox catalyst!

Fe, Cu, Mo:Fe, Cu, Mo: Electron-transfer

Redox proteins and enzymes

Oxygen carrying proteins

Nitrogen fixation

Biochemical Reactivity

Promotion of Appropriate Geometry Change acid/base character Change Redox potentials Change ionic concentration Formation of Unique species Formation of structural materials Activation of small molecules (NO)

Zinc and Copper

Zinc is found in more than 80 different enzymes. Carboxypeptidase

Catalyzes hydrolysis of peptide bonds Carbonic anhydrase

CO2 HCO3-

Copper Ceruloplasmin – blue-glycoprotein

Iron storage and oxidation/reduction Superoxide dismutase

Conversion of superoxide to peroxide to water. Also Lactase, ascorbate oxidase and plastocyanin

Alkali metals

Terrestrial distribution:Terrestrial distribution:

LiLi NaNa KK RbRb CsCs FrFr

0.060 nm 0.133 nm ionic radii

0.095 nm

Distribution in vivo:Distribution in vivo:

(Li)(Li) NaNa KK (Rb)(Rb)

Element % of total number of atoms in human body

Number of grams in a 70-kg Man

H 63 6580

O 25.5 48550

C 9.5 12590

N 1.4 1815

Ca 0.31 1700

P 0.22 680

K 0.06 250

S 0.05 100

Cl 0.03 115

Na 0.03 70

Mg 0.01 42

Fe < 0.01 7

Mn, Co, Cu,

Zn, Mo, V,

Cr, Ni, F, < 0.01 1

Si, Se, As

Role:

NaNa++

Extracellular fluid Osmotic balance „sodium pump” Acid-base balance Conformation of proteins

nucleic acids Electrical impulse of nerve system

Mg2+

3Na+ic + 2K+

ec + ATP4- + H2O

3Na+ec + 2K+

ic + ADP3- + HPO42- + H+

K+

Enzyme activator Conformation of proteins

RNA (replication)

Secretion of gastric acid Transmembrane potentials!

Complexes of alkali metals (Na+, K+)

Cyclic antibioticsValinomycinMonactinNonactin

polyethers syntheticcryptands

18-Crown-618-Crown-618-Crown-618-Crown-6

negative charge concentrated in cavity negative charge concentrated in cavity inside the moleculeinside the molecule

OO

OO OO

OO

OO

OO

18-Crown-618-Crown-618-Crown-618-Crown-6

negative charge concentrated in cavity negative charge concentrated in cavity inside the moleculeinside the molecule

OO

OO OO

OO

OO

OO

18-Crown-618-Crown-618-Crown-618-Crown-6

forms stable Lewis acid/Lewis base forms stable Lewis acid/Lewis base complex with Kcomplex with K++

OO

OO OO

OO

OO

OO

K+

18-Crown-618-Crown-618-Crown-618-Crown-6

forms stable Lewis acid/Lewis base forms stable Lewis acid/Lewis base complex with Kcomplex with K++

OO

OO OO

OO

OO

OO

K+

Alkaline Earth Metals

Terrestrial distribution:

Be Mg Ca Sr Ba Ra

Distribution in vivo:

Mg Ca

Be, Ba TOXIC!

Sr (not particularly toxic)90Sr accumulates in bones

Element % of total number of atoms in human body

Number of grams in a 70-kg Man

H 63 6580

O 25.5 48550

C 9.5 12590

N 1.4 1815

Ca 0.31 1700

P 0.22 680

K 0.06 250

S 0.05 100

Cl 0.03 115

Na 0.03 70

Mg 0.01 42

Fe < 0.01 7

Mn, Co, Cu,

Zn, Mo, V,

Cr, Ni, F, < 0.01 1

Si, Se, As

Mg2+

Plants chlorosis CHLOROPHYLL

nervous system (tetany) active transport (intracellular) enzyme activator (e.g. ATP-ase) Ca2+ antagonist

Ca2+

Inhibits Mg2+-activated enzymes Extracellular: clotting (10-3M)

Ca2+

prothrombin thrombin-fibrinogen-fibrin

Alkaline Earth Metals

ChlorophyllChlorophyll

The interactions between ATP, Mg2+, and arginine and lysine residues at the active site of an enzyme

Since all the negative charges in ATP are neutralized, ATP is readily approached by nucleophiles

- plasma proteins bones (hydroxyapatite)Ca5 (PO4)3 (OH)

- intracellular: enzymes10-8mol/dm3

- muscle contraction: troponin

- Calcium triggering: calmodulins (Ca-binding proteins)

largely helical and undergo helix/helix motion

Ca-binding hands: a short two-strand unit -sheet

CaCa2+2+ signal signal

metabolic controls

N T P

Protein phosphatase c-NMP

protein

DNADNA

New signals