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Role of Calcium

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Biochemistry of Calcium

Calcium in biology: earth crust, Sea water

Calcium in adult: as skeleton 1.2 Kg, daily intake 0.7-


0.8

99%-in structural; teeth, bone


1% body fluid: associated with enzymes. Complex
formation, free ions as electrolytes

Functions: Activation of enzymes, muscle contraction;


blood clotting; cell division; sensory function;
generation of energy (hydrolysis of ATP)
lonized CCa
(biologically active)

Ca complexed with
50% citrate, phosphate,
bicarbonate

10%

40%

Protein-bound
non-diffusible Ca
Deficiency of Ca2*; Metabolism disorder, Vomiting,
abdominal pain, Mascle contraction problem
Overload of Ca2t: complexation with fat; insoluble salt

Study:
Calcium in skeleton;
Calcium in activation of enzyme;
Calcium in contraction of muscle;
Calcium in blood clotting
Deficiency of Ca: Metabolism disorder, Vomiting,
abdominal pain, Mascle contraction problem
Overload of Ca2: complexation with fat; insoluble salt
Study:
1. Calcium in skeleton; Mineralisation of Bones and teeth.
Bone is a
mineralized connectivetissue.
It containa
organic (collagen protein) and inorganic (mineral)
-

HYDROXY APATITE, Ca10(Po4)6 (OH)2


Component,
2. Calcium in activation of enzyme;
Calmodulin is a Calcium binding regulatory protein mol wt
17000 Calmodulin can bind with 4 calcium ions
3. Calcium in contraction of muscle; Glycolysis metabolic
degradation of glucose
4. Gluconeogenesis-metabolic synthesis of
glucose.
5. in blood clotting: whenever our skin becomes broken,
Calcium
calcium works together with vitamin K and protein wll helps to
blood clotting.
Calcium is factor IV in coagulation cascade. Prothromlin (factor 10)
contains Gla(y Carboxy glutamate) Residues.
forms a bridge between Gla residues of prothrombin and
Calcium
membrane phospholipids of platelets
6. Messenger system
is necessary for transmission of nerve impulses from
Calcium
synaptic to post-synaptic region.
pre-
Secretion Hormones: for hormonal activation: Parathyroid hormone, Calcitonin
Calcium mediates secretion of Insulin, parathyroid hormone, calcitonin,
vasopressin,ete. from the cells
MYOCARDIUM
in myocardium, Ca++ prolongs systole. in hypercalcemia cardiac arrest is seen in
systole.
Caution: when calcium is administered intravenously, it should be given very
slowly.
Calmodulin, or calcium-modulated protein, is a calcium-binding8
protein found in the cytoplasm of all eukaryotic cells. It interacts with
many other proteins in the cell, and acts as a regulator or an effector
molecule in a wide variety of cellular functions.

Calmodulin (CaM) (an abbreviation for calcium-modulated protein)


is a multifunctional intermediate calcium-binding messenger
protein expressed in all eukaryoticcells. It is an intracellular target
of the secondary messenger Ca, and the binding of Ca* is
required for the activation of calmodulin. Once bound to Ca,
calmodulin acts as part of a calcium
signaltransduction pathway by
modifying its interactions with various target proteins such
as kinases or phosphatases
Calmodulin is a small, highly conserved protein that is 148 amino acids long
(16.7 kDa). The protein has two approximately symmetrical domains
globular
(the N- and C- domains) each containing a pair of EF hand motifs separated by
a flexible linker region for a total of four Ca binding sites, two in each globular
domain In the Ca~-free state, the helices that form the four EF-hands
are

collapsed in a compact orientation, and the central linker is

disordered;15IGLZ8! the Ca-saturated state, the EF-hand helices adopt an


in
one another, and the central linker
open orientation roughly perpendicular to
forms an extended alpha-helix in the crystal structure, ala but remains largely
disordered in solution The Cdomain has a higher binding affinity for
Ca than the N-domain.
Dalmadulin s a
monona MJS 17 Ka
Cm Sists ef 148 ami00acids
t laaulina r i
no atoin braptophan Conteins
te is hi io co e laisthde
op phonglalonina tn tgimane(82)
Calmbdulin
Bndiing
Camtains four a brAps es nde partein.
l e chab.el 6-bali.coS
CG2 s loomd toone r marr 9omanu oPohalice
Honal chang OCCAYs e n biäup SHs a lokam
a in q OVRr 301 IRephjetia
CA oAdioA Conft2uafion
Ceocmedhiona ChOme must pCCuurbetxe it Con
eglale m nnád. gotem
w
WED opand fo bndr Site, QtidrtKgdin 1ai lh
elootsaldte Side chain
March 0 nd.
Phde lbondp we
seint NAa utamae,
hspeople 0sporatë,
ond ho soid: CO O H
t nCetan my
peoplerwonhp
Aloel Yo hom
12 12

caldium

calcium
2015 Bnbing tr ofk Paeim- Dvgme
-b4 Chonale21,25 Jomodu Ra 1406
ncst nfeatua
ae lg bmio gcs Senae Calmoialin
9pou o apaoleio
tosenlated aftayansptiohH-has t , J15 15
RsprzpetaveChonga
lonisa Samaduln 1 Tial Ina be hspons ble
oRa pie

Jnachia Ca
M-4 active
JaschenSk
Sushale

g g m a Inacfu
Resgno-CM 4Ca
ComplesX achve
Recd
Kecogrition 2activation ap orgtae
Mechanism: Binding of Ca by the EF-hands causes an opening of the N- and
C-domains, which exposes hydrophobic target-binding surfaces,l These
interact complementarynonpolar segments on target proteins,
surfaces with
typically consisting of groups of bulky
hydrophobic amino acids separated by
10-16 polar and/or basic amino acids.18134 The flexible central domain of
allows the protein wrap around its target,
calmodulin
modes of
to although
known. "Canonical" targets of calmodulin, such as myosin
alternate
binding are
light-chain kinases and CaMKIL, bind only to the Ca-bound protein, whereas
some proteins, such as Nav channels and 1Q-motif proteins, also bind to
calmodulin in the absence of Caj1l Binding of calmodulin induces
conformational rearrangements in the target protein via "mutually induced
fit"12 leading to changes in the target protein's function.
Calcium binding by calmodulin exhibits considerable cooperativity
511 making
calmodulin unusual example of a monomeric
an (single-chain) cooperative
binding protein. Furthermore, target binding alters the binding affinity of
calmodulin toward Ca ions, 201211122 which allows for
complex allosteric interplay between Ca? and target binding
interactions.l This influenceofof target binding on Ca affinity is believed to
allow for Ca activation proteins that constitutively
are bound to
calmodulin, such as small-conductance Ca-activated potassium (SK)
channels
Ohitis
aCalcu tn e acfrafi.on of onygne
Jen 00iald tk relala
Shecellelay Ca t CatntP
aolend achivales spebte apsmas
Snegathc tuachan
Calmpdulin. Ccium- bind, ro gulalen
eted operetas an G ocaphoxs
Calmcdalinheiabtdcnsratitpeatse
gclre u.clazhde mchalolism Phasphodiaierate
clein AdonnlCgclase
N
pituphoylahion1 ytptom pacleins
erc 16
15 16
02
Cholol e24 Jomodiu Anol
Myain kinese-Soleial muscde136
muo u s ele
Ggta qen Non-mS Cle
Caltium meldhsophou
flux- phonalase ainase
Mg ATPase
SecgeHon-rhesina on
Noto tsensmle
Secrefion ttelease.
ih muscla CantncionS
g Caloum

Musele

Rbe fosallel) Coveed by Saxce lomma,


wamlacane

Myefi bril Saxcoplasm Lispd ss6are


3togen phawphefiaatin, ATP

sUN
e e
Hlomont or Ai
yau ejos as o
Morch ai o g a e a ans tate hipthne, dsiet ae haf om hs

2015
22
CKnant Thi lemot
Myofin Act

ATP
hopotin- C(Suburit)
aclina Qs Cal nodulin.
Role in animals (edit)
Calmodulin mediates many crucial processes such
as inflammation, metabolism, apoptosis, smooth muscle contraction,
intracellular movement, short-term and long-term memory and
the immune response2120 Calcium participates in an intracellular
signaling system by acting as a diffusible second messenger to the initial
stimuli. It does this by binding various targets in the cell including a large
number of enzymes, ion channels, aguaporins and other
proteins, Calmodulin is expressed in many cell types and can have
different subcellular locations, including the Cytoplasm
within organelles, or associated with the plasma or organelle
membranes, but it is always found intracellularly.2 Many of the proteins
that calmodulin binds are unable to bind calcium themselves, and use
calmodulin as a calcium sensor and signal transducer. Calmodulin can
also make use of the calcium stores in the endoplasmic reticulum, and
the sarcoplasmic reticulum. Calmodulin can undergo post-translational
modifications, such
as phosphorylation acetylation, methylation and proteolytic cleavage,
each of which has potential to modulate its actions.
Biologicalvoles of calciu

Calcium is major components of the structural


a

materials like bone and shell.


of skeleton occurs through the
Formation
calcium ion.
biomineralisalion of
units calcium forms the
In
such structural
like insoluble carbonate
biominerals
LISES OF CALCILM
Muscle contraction-Glycolysis - metabolic
degradation of glucose.
Gluconeogenesis metabolic
-

synthesis of
glucose
Blood cloting whenever our skin becomes
broken, calcium works together with vitamin
Kand proteinwillhelps to bloodclotting
Messenger system for hormonal activation
1 Parathyroid hormone
2 Calcitonin
Bone
Seashells

Eggshells Dental caries


Diseases
imanges

Rickets (defective
calcification):
Osteporosis
(cdemineralisation of
bone)
Hypercalcaemia

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