LECTURE ON BIOLOGICAL CHEMISTRY FOR 2 YEAR STUDENTS OF

DENTISTRY FACULTY :
Biochemistry o !o"e tiss#e: $rocesses o mi"er%&i'%tio"( )emi"er%&i'%tio" %")
remi"er%&i'%tio" $rocesses( there re*#&%tio" %") +io&%tio"s, Ro&e o the
+it%mi"s %") hormo"es i" the re*#&%tio" o !o"e tiss#e met%!o&ism
-LAN
., Commo" co"ce$ts
2, Chemic%& com$ositio" o !o"e tiss#e
/, Formi"* o !o"e
0, F%ctors 1hich i"&#e"ce o" met%!o&ism o !o"e tiss#e
2, B%sic *ro#$s o !o"e i&&"esses
Bo"e tiss#e is the special type of connecting tissue. It is necessary to distinguish a
concept bone as organ and bone tissue .
A bone as organ is difficult structural organization, in which together with specific
bone tissue enter periosteum, marrow, lymphatic and blood vessels, and nerves
and in a number of cases cartilaginous tissues.
Bone tissue is main component part of bone. It forms bony plates. Depending on a
closeness and location of plates the compact and spongy bone matter is
distinguished. In the bodies of long tubular! bones mainly there is the compact
bone matter. At epiphysis long bones, and also the spongy bone matter prevails
in short and wide bones .
Osteoblasts, osteosytes and osteoclasts %re the ce&&#&%r e&eme"ts o !o"e tiss#e
Bone composition and structure"
Bones or osseous material! serve a number of diverse purposes in the human
anatomy. In addition to providing structure, protection, and support for the organs
of the body, bones also house marrow, which produces blood cells. #ithin the
bones are also stored the calcium deposits which the body may access, via
resorption, when needed. Additionally, bones deto$ify the system, by removing
heavy metals, such as lead and arsenic, as well as other to$ins, from the
bloodstream. %sseous tissue itself is made of water about &'( of the bone weight!,
organic material about &') of the bone weight, most of which is the protein,
ossein! and inorganic minerals calcium, phosphorus, and magnesium
predominate, though iron, sodium, potassium, chlorine, and fluorine are also
present in small amounts!. *ost bones with the e$ception of those of the cranium!
are initially pre+formed in cartilage and are then ossified as the newborn develops.
,wo basic classification methods e$ist to categorize the bones of the body. ,hese
two classification systems are based upon anatomical location a$ial or
appendicular!, and shape long, short, flat, and irregular!. A$ial bones are the
eighty bones which lie along the central, vertical a$is of the body and support and
protect the head and torso and include the s-ull and the spinal
vertebral! column. Appendicular bones include the one hundred twenty+si$ bones
which comprise the appendages, including the shoulders and hips, arms and legs,
hands and feet, and fingers and toes. ,he shape classifications include long bones
such as the radius, humerus, and femur!, the short bones such as the carpals,
tarsals, and manual and pedal phalanges!, flat bones
such as the sternum, s-ull bones, and scapulae!, and irregular bones such as the
vertebrae!.
Articulated bones feature a cartilaginous covering at the .oints, which facilitates
the articulation by protecting the bones from shoc- and providing a softer bed to
which the synovial membrane may be attached. %steoarthritis is a common
disease among middle+aged and elderly people in which the articular cartilage
becomes inflamed ma-ing movement of the bones at the
affected .oints painful.
,he compact bone tissue serves as the outer shell of the bone and serves to protect
the inner core of spongy bone trebiculae, or substantia spongiosa!. ,he compact
bone shell is particularly thic- in the middle of the shaft in long bones in order to
protect the bone against bending. ,he compact bone is covered by the periosteum.
,he compact bone layer features a number of foramina openings! which allow the
nutrient vessels! to tunnel through to reach the marrow cavity and spongy bone
tissue within. *ost bones have one main nutrient vessel which, by branching into
a web of arterioles within the bone, feeds them, though the femur has two such
nutrient blood vessels. ,he bone has one foramen for the
entrance of each nutrient vessel, and foramina at the e$tremities for the produced
blood to pass out of the bone.
,he /aversian lamellae are layers of bone formed during the development of the
bone which contain the /aversian canals. ,hese canals house the blood vessels,
lymph vessels, nerves, and marrow of the bone.
,he 0ol-mann1s vessels are located within the /aversian canals in the /aversian
lamellae. ,hese vessels carry the nutrients which nourish the bone tissue and carry
newly generated blood cells and lymphocytes from the marrow
to the bloodstream.
,he osteocytes are bone cells which have lost their ability to produce bone
material. ,hese are the remnants of the osteoblasts which form bone tissue as the
bone is developing.
,he outer lamellae are the thin layers of bone tissue which are laid down as the
bone is formed. ,hey lie .ust below the periosteum and form the outer surface of
the compact bone tissue.
,he periosteum is the tough, vascular membrane which covers the surface of a
bone, e$cept for the articular cartilage. ,he periosteum contains the blood vessels
which supply nutrients to the bones enabling them to regenerate. ,he bones of the
s-ull feature no such periosteum, and so cannot regenerate themselves. ,he
periosteum also facilitates the regeneration of bone by
serving as a confining membrane for the deposition of new bone cells, insuring that
any regeneration of osseous material is added to the pre+e$isting bone.
,he diaphysis, or shaft, of a long bone features a shell of compact bone surrounded
by the periosteum, a cartilaginous membrane which contains the blood vessels
which provide nutrients to the bone. ,he diaphysis is separated from the epiphyses
ends! of the bone by the epiphyseal line.
#hen bones form, calcium salts are first deposited within the shaft diaphysis!,
and this calcification spreads outward to the ends of the bone epiphyses!. As this
progresses, the periosteal membrane produces a networ- of fibrils osteoblasts! in
front of this advancing line of calcification, which provides a mesh framewor- for
the ensuing calcification. %nce this calcified cartilage has developed, the
periosteal membrane sends blood vessels into the bone which carry nutrients as
well as regulatory cells -nown as osteoclasts.
,he osteoblasts and osteoclasts wor- together to replace the calcified cartilage
with true, osseous material. ,his process is carried out on the ends epiphyses! of
the bones as well, though a layer of uncalcified cartilage demarcates the epiphyses
from the diaphysis until later in the life of the bone. %nce the true bone has
developed, the center becomes hollowed out, which allows for the development of
the marrow and the spongy tissue layer trabeculae!. ,he growth and development
of the bone is regulated by a hormone secreted by the pituitary gland, with new
growth ta-ing place at the epiphyseal line. At some stage, however, hormones,
secreted by the testes in the male and ovaries in the female, cause this bone growth
to cease, whereupon the epiphysis fuses to the diaphysis. Beyond this point, which
usually occurs earlier in females, the bone undergoes simultaneous resorption
where it brea-s down and re+absorbs osseous material! and reconstruction.
/ealthy bone is constantly undergoing resorption and reconstruction, though, in
the elderly, the reconstruction of bone is somewhat diminished, ma-ing healing of
fractures slower.
,he spongy bone tissue also called the substantia spongiosa, or trabeculae! is the
porous, inner layer of bone beneath the compact bone shell. 2o called because of
its sponge+li-e structure of bony fiber, the spongy layer is actually very strong and
resistant to compressive damage. ,he spongy bone is particularly prevalent in the
ends of long bones, where they are more sub.ect to such damage.
%steoporosis is a disease common in post+menopausal women as well as others
who do not get sufficient calcium and phosphorus in their diets! which degrades
the structural integrity of the spongy tissue, causing
it to become brittle and more li-ely to chip or fracture.
,he epiphysis plural, epiphyses! is the end of a developing bone. It is
distinguished from the non+developing segment of the bone by the epiphyseal line.
#hen bones form, calcium salts are first deposited within the shaft diaphysis!, and
this calcification spreads outward to the ends of the bone epiphyses!. As this
progresses, the periosteal membrane produces a networ- of fibrils osteoblasts! in
front of this advancing line of calcification, which provides a mesh framewor- for
the ensuing calcification. %nce this calcified cartilage has developed, the
periosteal membrane sends blood vessels into the bone which carry nutrients as
well as regulatory cells -nown as osteoclasts.
,he endosteum is the layer of bone which lines the inner marrow! cavity within
the long bones which houses the bone marrow. It is distinguished from the
periosteum, which is the e$ternal membrane which covers the surface of the
compact bone tissue.
,he marrow also called medullary! cavity is the region within the bone which
houses the marrow, responsible for generation of blood cells. ,he marrow in
newborns and children is generally red, turning yellow in adults in all bones with
the e$ceptions of upper ends of the humerus and femur and in many of the flat
bones of the s-ull, vertebrae, ribs, sternum, and hip. ,he red marrow, also -nown
as myeloid tissue, produces all types of blood cells e$cept for lymphocytes and
monocytes which are formed primarily in the lymph nodes and the spleen!.
Anemia is a disease in which the myeloid tissue cannot produce sufficient red
blood cells as when the body does not get enough of the mineral iron!, with the
chief symptom being chronic fatigue.
3irst the words. Bone is a substance. ,hings can be made out of the material called
bone. And, bones are s-eletal parts which might not actually be made out of bone
the substance!. 2har-s have s-eletons with lots of bones and those bones are not
made out of bone. Baseball diamonds are not made out of diamond at least not in
our nec- of the woods!.
Bones - The Substance
Bone is a comple$ building material that can be made by a variety of tissues and
not in a single way. It is easier to thin- of tissues placing re4uests or signaling for
bone. ,hat signal sets off processes that do the actual bone manufacture.

2ome bone is built up in layers between or beneath specialized tissue layers. ,hat
tissue is typically tough and not too unli-e canvas in thic-ness and toughness. ,he
plates of the s-ull are made wholly from bone layered between two such
membranes.
,he shafts of long bones get thic-er by deposition of bone beneath an encircling
tube of similar tissue.
Bone is also of differing composition. 2ome is made fast and on the fly with little
organization 5woolly bone5!, as is the case with fractures healing. 2ome is highly
organized in layers lamellar bone! and some is built up of laminated tubes, li-e a
bundle of stic-s, within the other -ind of bone /aversian!. Bone can be dense
5compact5!, or 5spongy5.
6oo-ing through the microscope at slivers of bone such as ta-en from a bone near
the outer surface but in a spongy area, we can see a mi$ of types. ,he spongy bone
is bone with lots of spaces. ,hose spaces are generally sprin-led with blood
tissues. Bones do not only contain blood, they contain blood vessels and much of
the machinery for ma-ing blood cells.
%n the far right we see some lamellar bone, loo-ing li-e strata of geologic layers
of earth. Into such bone, cones of cutting blood vessels penetrate. ,hey
then organize bone around their path of penetration forming bone in long layered
tubes. #e see those in cross section on the left. ,hey are called /aversian ,ubules
ta-e a wild guess who they are named after!.
7ells are seen in layers around a central canal /aversian 7anal!. 8adiating micro
tubules reach out intercommunicating.
7ells within bone osteo! can ma-e 5blast5! or degrade and remove 5clast5! bone
substance. %steoblasts lay down bone and osteoclasts digest bone. /ow active is
all this9 #ell, depending on who you are, roughly one third of the bone you had
yesterday isn1t the bone you have today.
,he layering and bundles of layered tubes are of cells and sheets of tissue made of
very tough fiber called bone collagen. A bone with all of its calcium leached out
can be tied in a -not. %n and through that structure, a very special crystalline form
of calcium is formed called hydro$yappetite. ,hat stiffens the bone to ma-e it hard.
Bone gets strength from two things.
&! #hat it is made from -ind of bone!, and
:! /ow it is shaped and organized.
/ydro$yappetite figures in both aspects of strength. ,he first is -ind of obvious.
2ome stuff is tougher than other stuff. But shape is very important. ,ubes are
stronger than rods. ,ension and compression struts vastly support structures loo-
at power towers!. As with certain crystals + such as those used in phonographs
remember those! + when pressure is placed on them, they polarize and e$hibit an
electric charge. A needle .iggling in a plastic trac- while pressing against a crystal
will reflect the .iggling as a fluctuating charge which magnified gives us music +
and we listen.
,he compression of forces of daily activity on hydro$yappetite gives us zones of
charge to which the osteoblasts listen. ,hey respond by putting more bone
substance where forces generate such charges. #here such charges fail to form,
bone + always being dissolved + wheedles away. ,he form of bone follows
function. In other words, as was spo-en by /ypocrites a few years ago, 5,hat
which is not used, wastes away.5 ,he paraphrase is, 5;se it or lose it.5
,his had to be rediscovered when perfected devices which held fractured bone
pieces absolutely rigidly, better than ever before ... produced poorer healing.
#ithout 2%*< movement, bone formation is not very good.
7alcium
7alcium is an important substance beyond mere bone structure. In ionic form the
molecular water dissolved form! it is a charged atom as 7a
==
which means it has
charge that pairs it with negative charged things such as two %/
+
hydro$yl!
molecules or phosphate as >%
(
?
. In this charged form it is used to regulate, control
or initiate processes such as nerve conduction, muscle contraction, hormone
release among other things. It is very tightly -ept at optimum in the blood + even if
that means ta-ing calcium from bones. 7alcium is the stuff that leaves water spots
on dish ware or which ma-es bathtub rings when combined with certain
substances. ,hat is, it easily precipitates. @+rays of in.ured or inflamed tissue may
show deposits of calcium. ,hat does not mean calcium 7A;2<D the problem, but
more li-ely that calcium is precipitating due to the problem.
Indeed, the combined levels of 7a
==
and >%
(
?
found normally in the blood e$ceed
levels which can be achieved in water without precipitating. Blood is hyper
saturated with calcium by means of other substances which stabilize calcium in
solution. An interesting complication of this fact to babies + especially preemies + is
that I0 fluids used to maintain babies who cannot eat! cannot contain <I,/<8
enough 7a
==
%8 enough >%
(
?
to sustain needs. 7hildren can get a baby form of
ric-ets which may loo- li-e bone loss with fractures. ,o get around this, if an I0 is
needed long term, solutions with high calcium have to be alternated with solutions
of high phosphate. If the correct amounts of B%,/ were placed in a single
solution, the calcium phosphate would solidify in the bottle.
#hen calcium levels in the blood are off by substantial amounts then something
else must be at the core of the matter" low protein, high protein, -idney disorder
etc. ,he people who manage calcium and those other difficult blood salts and
-idney function are the ones with tall foreheads, out of control hair and who horde
all the bac- issues of the Aournal of 7linical Investigation
Diphosphonates are drugs which deliver dual phosphate molecules. >airs of
phosphates glom onto hydro$yappetite li-e egg dye on an egg. ,hat tends to
5stabilize5 the otherwise very rapid turnover of the crystal. #hen there is a process
that draws away calcium, the diphosphonates protect the crystals. But they can get
in the way of build up when the process is in the direction of accumulation. Bewer
more clever chemistries are being used to see if the plusses can be made to
outweigh the minuses. ,he very uneven results seen with these drugs as a class
reflects the inconsistency of the application. ,here is tremendous variation and an
e$perienced professional is needed to -now if it is helping or hurting.
Body Distribution of Calcium and Phosphate
,here are three ma.or pools of calcium in the body"
Intracellular calcium: A large majority of calcium within cells is
sequestered in mitochondria and endoplasmic reticulum. Intracellular
free calcium concentrations fluctuate greatly, from roughly 100 nM to
greater than 1 uM, due to release from cellular stores or influx from
extracellular fluid. These fluctuations are integral to calciums role in
intracellular signaling, en!yme acti"ation and muscle contractions.
Calcium in blood and extracellular fluid: #oughly half of the
calcium in $lood is $ound to proteins. The concentration of ioni!ed
calcium in this compartment is normally almost in"ariant at
approximately 1 mM, or 10,000 times the $asal concentration of free
calcium within cells. Also, the concentration of phosphorus in $lood is
essentially identical to that of calcium.
Bone calcium: A "ast majority of $ody calcium is in $one. %ithin
$one, &&' of the calcium is tied up in the mineral phase, $ut the
remaining 1' is in a pool that can rapidly exchange with extracellular
calcium.
As with calcium, the ma.ority of body phosphate appro$imately CDE! is present
in the mineral phase of bone. ,he remainder of body phosphate is present in a
variety of inorganic and organic compounds distributed within both intracellular
and e$tracellular compartments. Bormal blood concentrations of phosphate are
very similar to calcium.
F&#3es o C%&ci#m %") -hos$h%te
*aintaining constant concentrations of calcium in blood re4uires fre4uent
ad.ustments, which can be described as flu$es of calcium between blood and other
body compartments. Three or*%"s $%rtici$%te i" s#$$&yi"* c%&ci#m to !&oo)
%") remo+i"* it rom !&oo) 1he" "ecess%ry:
,he sm%&& i"testi"e is the site where dietary calcium is absorbed.
Importantly, efficient absorption of calcium in the small intestine is
dependent on e$pression of a calcium+binding protein in epithelial cells.
Bo"e serves as a vast reservoir of calcium. 2timulating net resorption of
bone mineral releases calcium and phosphate into blood, and suppressing
this effect allows calcium to be deposited in bone.
,he 4i)"ey is critcally important in calcium homeostasis. ;nder normal
blood calcium concentrations, almost all of the calcium that enters glomerular
filtrate is reabsorbed from the tubular system bac- into blood, which preserves
blood calcium levels. If tubular reabsorption of calcium decreases, calcium is lost
by e$cretion into urine.
Chemic%& Com$ositio" o !o"e
,wenty+five percent of the dry weight of the intercellular material in bone is
organic matri$. About CFE of the organic matri$ is collagen, the rest is
proteoglycan, with small amounts of lipids and peptides. ,he organic matri$
is called osteoid.
In addition to collagen there are several important glyco+proteins. %ne is bone
sialoprotein composition, DGE protein, :GE sialic acid, )GE carbohydrate!.
,he large number of acidic amino acids and sialic acid may e$plain its
cation binding properties.
:GE of the non+collagen protein is osteocalcin, also called bone 1Hla1 protein. It is
a vitamin I dependent calcium binding protein containing carbo$yglutamic
acid. It strongly binds to 7a hydro$yapatite.
2eventy+five percent of the dry weight is mineral.
Chemistry o I"terce&&#&%r S#!st%"ce
A, Or*%"ic M%tri3
&. 7ollagen
a. protein high in content of AA, glycine, proline,hydro$yproline and many AA
missing
b. >rotein heli$ is linearly oriented+) chains twisted around each other in a fibril. /
bonding between the chains.
:. Hround 2ubstance
a. originally thought to be amorphous but now, a crystalloid
b. 7hemically, it is a mi$ture of sulfated and non sulfated mucopolysaccharides or
glycoaminoglycans HAH!. A connective tissue contains both the collagen and
HAH but
depending upon the amount of HAH determines degrees of decalcification.
c. 8elationship between protein and carbohydrate proteoglycan+>H6J!
Believe the space between cells is filled with an a4ueous solution colloidal! of
>H6J and fi$ed within this are insoluble collagen fibers in the form a
heli$. ,hey are oriented linearly, maintained in place by the
electrostatic forces of the ground substances and other collagen fibers.
B, I"or*%"ic M%tri3
&. lattice structure is that of hydro$yapatite
:. not a single homogeneous compound
It is a crystalline with an ultramicroscopic or colloidal dimension. ,he effective
surface
area is very large. ,he chemical composition is only appro$imate as the 7a, >%(
and %/ can be replaced. 0ariability depending on diet contents of
various ions.
7annot be distinguished between those ions in the lattice and ions on crystals
adsorbed
6ayer or hydrations shells.
7. *ineral composition of bone
,he mineral is mostly calcium phosphate in the form of hydro$yapatite crystals
found in and along the collagen fibers. 7alcium hydro$yapatite is in
the form of comple$ microcrystals, which have a periodic repetition
of the basic structural pattern of the constituent ions -nown as the unit
cell. ,he unit cell has the formula 7a
&G
>%
(
!
K
%/!
:
which is a right
rhombic prism when stac-ed and forms a he$agonal Iattice.
Bone mineral apatite is not a pure substance or crystal. ,he theoretical molar ratio
of 7a"> for hydro$yapatite is &.KL. /owever, substitution of another
cation for 7a, or anion for >G( or %/ can occur during formation or
by e$change between the crystal and the surrounding li4uid media.
,he 7a"> ratio in bone is appro$imately &.F. 2mall amounts of 7%)?, %/+, Ba=,
3+ and citrate+: are found in bone mineral.
D. 8elationship between crystal and ions in e$tracellulfluid <73!
&. very comple$ and certainly not well defined
:. apparently a metastable supersaturated solution of the concentration of ions in
<73 indicates that bone formation should occur but does not. ,his
concentration of ions, e$pressed as the product of the 5common ions5 in
solution specific for every solid! is -nown as the solubility product
constant. 2olutions containing concentrations of common ions higher than
the value are supersaturated and form a precipitate. >recipitation does not
occur due to factors in the body which will interfere with the state of
saturation. ,hese are" 7helating agents, high ionic strength, and presence of
colloids++all of which decrease the saturation. <$changing of <73 7a and
>%( with the same or different ions on, in or at the surface of the crystal is
occurring to a considerable e$tent very rapidly.
). when e$change occurs no change in charge occurs
<. 0ariable composition of bone mineral
,he composition of bone mineral is not fi$ed. 7ertain ions, if present, can become
incorporated into the bone either during new bone formation or
remodeling. ,his may also occur by ionic e$changes between bone
and the fluids surrounding the bone.
#hen osteoid is mineralizing fluoride in the blood will be incorporated into the
mineral by substitution of one of the two %/+ groups. ,he resulting
mineral, called fluorapatite is harder, less soluble and more resistant to
bone resorption. ,his is also one of the mechanisms by which
fluoridation of the water supply decreases dental caries when fluoride
is incorporated into enamel and dentin.
If lead, barium or strontium are present, they can be incorporated into bone by
substituting for a small fraction of the calcium normally incorporated.
,he resulting bone is unusually dense bone, which resists resorption.
3urthermore, these to$ic metals can be released into the blood by
e$change reactions over long periods of time. 2rF%, a highly
radioactive element, is a product of 5dirty nuclear bombs5. ,he fallout
of 2rF% becomes incorporated into our food chain. If ingested,
especially by children, the bone becomes labeled with 2rF%. ,he local
radiation is -nown to cause bone and blood cancers. 2mall amounts of
Ba= and I= and other cations can substitute for 7a, and /7%)+,
2%(? and other anions can substitute for %/+ or >G(. ,his
phenomenon e$plains the variable composition of bone.
An e4uilibrium or e$change reaction e$ists between the mineral and surrounding
fluids. If the e$change is for identical ions, e.g. 7a for 7a, we call it a
homo+ionic e$change. /omoionic e$changes are without
conse4uence. /owever, if an isotope of normal bone constituent (D+
7a, ):+p &C+%! is administered, the bone will be labeled both by
e$change and new bone formation.
/eterionic e$changes can also occur between similar ions, e.g. 7a and >b, > and
%/, 7%) and %/, etc.
5, Bo"e orm%tio"6 Mi"er%&i'%tio"
,he description of mineralization given below is our best hypothesis to date. ,he
evidence for this is still wea- but it does present a complete story.
A. 2ynthesis of organic matri$ with many negative charges.
B. Accumulation of mineral.
Hlycogen levels in osteoblasts decrease during mineralization. ,he complete
o$idation of glycogen produces A,>, but some of the available energy
is transduced by bringing the mitochondrial 7a &GG$ higher than in
the cytoplasm! ratherAthan forming A,>.
7. 0esicles are formed.
/ow they are formed is un-nown but they can be isolated from osteoblasts. ,hey
have a phospholipid rich membrane and contain a 7a+>+lipid
comple$, A,>, >%(, >:%L and al-aline phosphatase. ,he *g is
believed to inhibit hydro$yapatite formation.
At some un-nown signal the 7a rich vesicles in the osteoblasts fuse to osteoblast
membrane and then bud off and spill out into the organic matri$. ,he
7a and >%( concentration increase.
D. *ineralization of the matri$ re4uires ) factors.
&. 2ome factor to increase the 7a $ > ion product to cause spontaneous
precipitation.
:. A nucleation site to begin crystallization of hydro$yapatite.
). 8emoval or inactivation of factors inhibiting spontaneous crystal formation and
growth.
<. Increasing the7a $ > ions product
,he organic matri$ has many negative charge loci, especially on the carbo$yl and
sulfate group of the >roteoglycans present. %steocalcin and bone
sialoprotein also have centers of negative charges capable of attracting
or hording 7a.
,he phosphate concentration may be increased by al-aline phosphatase present in
calcifying bone acts on phosphate esters to produce phosphate. ,he
M7aN and M>%(N both increase and e$ceed the solubility for calcium
phosphate.
3. Bucleation sites
%ne theory suggests that collagen is the one and only important nucleation site in
bone. %thers suggest osteocalcin is the nucleation site because it has
an affinity for 7a hydro$yapatite but not amorphous calcium
phosphate. 2till others suggest the sialoprotein in the matri$ vesicle is
the site of crystallization.
H. 8emoving inhibitors
*g in the matri$ vesicle is lost, perhaps by comple$ing with A,>, allowing
amorphous calcium phosphate to be converted to hydro$yapatite.
>yrophosphate also inhibits hydro$yapatite formation. >erhaps
al-aline phosphatase hydrolyze pyrophosphates.
5I, Bo"e resor$tio"
#e understand less about the details of bone resorption than we do of bone
formation. ,he following is only a hypothesis combining the thin-ing of
many researchers. %steoclasts produce both citric and lactic acids, which are
secreted into the organic matri$. 6ysosomes or phagocytic vacuoles are
released, or gain access to the intercellular space. ,he acids both solubilize
the calcium and activate the acid hydrolases from the lysosomes.
7ollagenase action starts the disorganization and solubilization of the
matri$. ,he partially digested organic matri$, and some mineral is ta-en up
by the osteoclast and digestion completed in phagocytic vacuoles. ,he
products of digestion can be put into the circulation, and e$cept for the
hydro$yproline and hydro$ylysine, re+used.
7irculating macrophages also have collagenase. It is suggested that when bone is
to be resorbed, the osteoblast a tissue macrophage! produces a chemotactic
substance on its surface. ,he circulating phagocytes, recognizing bone as a
foreign body, are attracted to bone. ,he circulating macrophages may secret
the acid and collagenase while the osteoblast may be only involved in the
final steps of the hydrolysis of the matri$.
5II, Bo"e t#r"o+er
,he processes of bone formation and resorption appear to be a physiologically
coupled processes. In the growing child, formation is greater than resorption.
In the adult they may be e4ual, but more often bone resorption is somewhat
greater than formation. ,hus there is a gradual decrease in bone density with
aging.
Bew bone formation could be the result of activation of resting osteoblasts or the
proliferation and differentiation of pre+ osteoblasts. ,he signal may be local
factors mechanical or chemical stress!, a systemic or local hormone, or
some coupling factor resulting from bone resorption.
Bone resorption presumably results from activation of osteoclasts or macrophages
by local f factors, hormones or some coupling factor resulting from bone
formation.
/ard to calcify"
Brain and 6iver
<asy to calcify"
Bone, cartilage, -idney, blood vessels
5III, Ecto$ic c%&ciic%tio":
*ost tissue can, but seldom, calcify. >resumably, this may be related to the type of
collagen present in most tissues. ,he collagen in bone is the most calcifiable,
and of course does mineralize. Blood vessel walls and -idney can
pathologically or with aging, calcify. ,his suggests the collagen is somewhat
different in those 1easy to mineralize1 tissues. #e have not
identified this difference. #hen the arterial wall develops a pla4ue or an organic
5matri$5 with fibers, calcium phosphates can precipitate. ,he framewor- or
matri$ in the blood vessel wall is probably a mi$ture of accumulated
cholesterol, lipoprotein, platelets and fibrinogen'fibrin fragments.
Hormo"%& Co"tro& Systems
*aintaining normal blood calcium and phosphorus concentrations is managed
through the concerted action of three hormones that control flu$es of calcium in
and out of blood and e$tracellular fluid"
-%r%thyroi) hormo"e ser+es to i"cre%se !&oo) co"ce"tr%tio"s o c%&ci#m,
*echanistically, parathyroid hormone preserves blood calcium by several ma.or
effects"
2timulates production of the biologically+active form of vitamin D within
the -idney.
3acilitates mobilization of calcium and phosphate from bone. ,o prevent
detrimental increases in phosphate, parathyroid hormone also has a potent
effect on the -idney to eliminate phosphate phosphaturic effect!.
*a$imizes tubular reabsorption of calcium within the -idney. ,his activity
results in minimal losses of calcium in urine.
5it%mi" D %cts %&so to i"cre%se !&oo) co"ce"tr%tio"s o c%&ci#m, It is generated
through the activity of parathyroid hormone within the -idney. 3ar and away the
most important effect of vitamin D is to facilitate absorption of calcium from the
small intestine. In concert with parathyroid hormone, vitamin D also enhances
flu$es of calcium out of bone.
C%&cito"i" is a hormone that functions to reduce blood calcium levels. It is
secreted in response to hypercalcemia and has at least two effects"
2uppression of renal tubular reabsorption of calcium. In other words,
calcitonin enhances e$cretion of calcium into urine.
Inhibition of bone resorption, which would minimize flu$es of calcium from
bone into blood.
Although calcitonin has significant calcium+lowing effects in some species, it
appears to have a minimal influence on blood calcium levels in humans.
Hormo"%& re*#&%tio" o !o"es mi"er%&i'%tio" %") )emi"er%&i'%tio"
Hormo" mi"er%&i'%tio" )emi"er%&i'%tio"
>arathyroid
7alcitonin
,hyro$ine
2omatotropin
7orticosteroids
=
=
=O
==
O
==
O
=
=
=O
%steogenesis imperfecta brittle bone disease! + caused by insufficient
production of good 4uality collagen to produce healthy, strong bones.
3ibrodysplasia ossificans progressiva + disease of the connective tissue,
caused by a defective gene which turns connective tissue into bone.
Reere"ces,
&. Aohn *c *urry, *ary <. 7astellion. Heneral, %rganic and Biological
7hemistry.+ Bew Aersy" >rentice /all, &FF:.+ LK( p.
:. Aohn #. 2uttie. Introduction to Biochemistry. P Bew Jor-" /olt,
8inehart and #inston, Inc., &FF:.+ )K( p.
). 8obert I. *urray, Daryl I. Hranner. /arperQs illustrated
Biochemistry. P India" International <ducation, :GG).+ KF) p.
(. 0I *alhotra. Biochemistry for students. P India" Aaypee Brothers,
*edical >ublishers 6,D, &FFC. P ))(p.
D. 6ehninger A. >rinciples of Biochemistry. P Bew Jor-" #orth
>ublishers, Inc., &FC:. P &G&G p.
K. 2tryer 6. Biochemistry. P Bew Jor-" #./.3reeman and 7ompany,
&FCC. P &GCK p.