Everything about Calcium . Done for: Vitamins and Minerals in Nutrition Lecture - just university .

1. Vitamins And Minerals In Nutrition
NF773
2018-3-14
Calcium
Supervisor : prof. sana janakat
By : Haya abumater

2. Calcium
• Most abundant mineral in the human body
• Total Calcium in the human body is about 1 to 1.5 kg, 99% of
which is found in bone together with phosphate.
• Small amounts are found in soft tissue & 1% in extracellular
fluid .

3. Chemical properties of Ca2+
• Belong to ( group IIA ) .
• The biological Activity & regulation of Ca2+ are influenced by
Concentration of ionized or free Ca2+ in solution.
• Binding of Ca2+ to the protein components of cell membrane :
- Change the fluidity of the membrane .
- Allow passage of ions .

4. Calcium is found in blood plasma :
• Bound to plasma proteins (albumin) (35-40%)
• As free-ionized (45-50%)
• Complex with sulfate , phosphate or citrate 10%

5. Sources
• The best sources of Ca2+ are:
• milk and dairy products.
• Sea food ( salmon , sardines with
bones , oyster .
• Vegetables : turnip ,
broccoli , Kale .
• Legumes : tofu .
• Dried fruits .
https://sacramentodentistry.com/oral-health/got-calcium/ access at 8-3-
2018

6. Digestion
Calcium as insoluble salt
food
dietary
supplements
Acidic
PH
1 hour
Free soluble Ca2+

7. Absorption
Tow transport process are responsible for the absorption :
1. Transcellular transport
• Epithelial Ca channel .e.g: TRPV6
• Calbindin D9K , CRP.
Stimulated by :
- Calcitriol ( Vitamin D )
- Low Ca diets

8. 2- Paracellular transport :
occurs between cells The process allows the movement
(Diffusion) of Ca .
Occurs when :
- High [ Ca ] in lumen.
- Gradient of [ Ca ] between the lumen and basoletral side .

9. Figure 1
Ca digestion ,absorption , transport
Gropper et al.2009

10. Absorption
Mechanism of calcium absorption:
• About 40% of dietary calcium is absorbed from the gut
• Absorption occurs from the first & second part of duodenum
• Absorbed against a concentration gradient & requires energy

11. Table 1 :
Interaction between Calcium and selected Nutrients/Substances
Whose Absorption
May be Inhibited
by Excessive Ca
Enhancing Urinary
Ca Excretion
Inhibiting Ca
absorption
Enhancing Ca
absorption
IronSodiumFiberVitamin D
Fatty AcidsProteinPhytateSugars and sugars
alcohols
CaffeineOxalateProtein
Excessive divalent
cations (Zn,Mg)
Unabsorbed fatty
acids

12. Transport
• Calcium is Transported in the blood via :
1- bound to proteins . ( albumin & prealbumin ) 40%
2- Complex with sulfate , phosphate or citrate . 10%
3- Found free (Ionized) in blood. 50%
* the total calcium and ionized calcium measurements are available in many
laboratories

13. Functions of Calcium
• Formation of bone mineral .
• Regulation of enzyme activity .
• Second messenger in the cell .
• Nerve conduction
• Blood coagulation

14. Bone mineralization
• 99% of total body Calcium is found in bone And teeth.
• Ca2+ is found in the body as :
Calcium Phosphate compound Hydroxyapatite
( Ca10(PO4)6(OH)2)
Functions of Calcium …

15. Bone mineralization
Types of Bone Tissue :
• cortical bone
• trabecular bone
Trabecular and Cortical Bone (Cowin, 2001)
https://www.researchgate.net/figure/Trabecular-
and-Cortical-Bone-Cowin-2001_fig1_230822645
8-3-2017

16. Figure 2 : Characteristics of cortical and trabecular Bone .
Trabecular BoneCortical Bone
Spongy appearanceCompact or dense
Represents about 20% to 25% of bone in
the body .
75% to 80% of total bone in the body
Consists of an interconnected system of
protein (mostly collagen)
Consist of layers of mineralized protein
( mostly collagen )
Found in high conc. In the axial skeletonFound on the surfaces of all bones and
the shaft of long bones of the limbs and
wrist .

17. Calcium Binding protein in Bone
• Osteonectin ( the most aboundant noncollagenous protein in bone )
• Gla protein ( Vitamin K dependent protein )
• Osteocalcin ( biomarker of bone formation in serum)
• Protein S ( the deficiency associated with osteopenia )

18. 3 types of bone cells :
• Osteoblast :
- called (Bone building cells)
- Produce matrix
- secret collagen and ground substance .
- become ostocytes .
• Osteocytes :
- Star shaped
- mature bone cells
• Osteoclasts :
- Phagocytic cell
-role in increasing blood [Ca2+ ]
-contain lysosomes and enzymes capable of breaking down.

19. • Osteoblasts cell (gray blobs forming an oval) create
new bone tissue.
https://www.sciencenewsforstudents.org/article/bo
nes-hard-scaffold-influencing-other-tissue
access at 7-3-2018
https://www.sciencephoto.com/media/301684/view
access at 7-3-2018

20. Osteocytes cells, instructing the other bone cells what
to do.
https://www.sciencenewsforstudents.org/article/bo
nes-hard-scaffold-influencing-other-tissue
access at 7-3-2018
http://www.anatomybox.com/tag/false-color/
access at 7-3-2018

21. Scanning electron micrograph of activated
osteoclast and resorption pits.
https://boneresearchsociety.org/resources/gallery/3
8/
access at 7-3-2018

22. Functions of Calcium …
• Second Messenger
: are molecule that relay signals from receptors on the cell surface
to target molecules inside the cell.
Ca2+ acts as a second messenger in two ways:
• it binds to an effector molecule, such as an enzyme, activating it.
• it binds to an intermediary cytosolic calcium binding protein such
as calmodulin.

23. Figure 3: the role of
Calcium and IP3 in
Signaling.
pathwhttps://www.youtube.com/wa

24. • Cytosolic Ca2+ can bind to
cellular Ca2+ binding proteins,
including Camodulin
Activate cellular Kinases and
Enzymes
• Calmodulin is a calcium binding
regulatory protein .. Contain 4
calcium-binding (EF-hand).
Full-length Ca4-calmodulin
X-ray: pdb 1cll; Chattopadhyaya, R., Meador, W.E., Means,
A.R., Quiocho, F.A. J. Mol. Biol. 228, 1177-1192 (1992)
accses at 7-3-2018
• Activation of enzymes
Functions of Calcium ..

25. The EF hand
https://www.quora.com/What-is-the-
difference-between-EF-Hand-and-helix-
10/2/2018turn-helix-protein-motifs
• Found in large family of Ca2+-binding
protein , such as : calmodulin and
calbindin D .
Composed of :
• 10- to 12-amino acid alpha helices
• 12-residue calcium binding loop
region .
* most EF- hand proteins at position
12 is glutamate .
Ca2+

26. • Muscles
• Calcium mediates excitation & contraction of muscles
- interacts with troponin C to trigger muscle contraction
- activates ATPase, increases action of actin and myosin and
facilitates excitation-contraction coupling.
- decreases neuromuscular irritability.
- Calcium deficiency causes tetany.
Functions of Calcium…

27. • Nerve conduction
It is necessary for transmission of nerve impulses .
• Blood coagulation
- Calcium is known as factor IV in blood coagulation process
- Prothrombin contains γ-carboxyglutamate residues which
are chelated by Ca2+ during the thrombin formation
Functions of Calcium…

28. Regulation of Calcium concentrations
Extracellular
Hormones involved in Ca2+ homeostasis :
• Parathyroid hormone(PTH)
• Calcitriol
• Calcitonin

29. Stimulus :
Falling blood Ca level
Parathyroid
glands release
PTH
PTH
Increase
Ca2+ uptake
in kidneys.
Increase Ca2+
uptake in
.intestines
Stimulates
Ca2+ release
from bone .
Active
vitamin D
Stimulus :
Rising blood Ca2+ level
Parathyroid
glands release
calcitonin
Calcitonin
Stimulates
Ca2+ deposit
in bone .
reduces Ca2+
uptake in
.intestines
reduces
Ca2+ uptake
in kidneys.
Figure 4: Blood Ca2+ regulation by PTH & Calcitonin

30. Blood
Low [Ca]
Gastrointestinal
Tract
Basolate
membrane
Brush border
membrane
Calcitriol
Ca2+
Figure 5: Blood Ca2+ regulation by calcitriol in response to low blood [Ca2+ ] .

31. Table 2: A summary of the Effects of PTH , calcitiol ,calcitonin
on Ca2+ Balance.
CalcitoninCalcitriolPTH
Serum calcium
*
Bone Calcium
Renal Ca2+
reabsorption
No effect
Intestinal Ca2+
absorption
* Works with PTH

32. Regulation of Calcium concentrations
Intracellular
• Ca2+ enters cells by diffusion of channels and exerts its
actions.
• Ca2+ can be removed from the cytoplasm
in tow ways :
1- ATP-dependent pumps use Mg++ and Na++ to export Ca2+ out
of the cell, and Atpase .
2- pumped can sequester Ca2+ in organelles such as the
endoplasmic reticulum or mitochondrion.

33. :Figure 5
Regulation of intracellular [calcium]

34. Lower [Ca2+ ] By
• Buffering free Ca2+ via molecular sequestration.
• compartmentalization* of Ca2+ through uptake in to cellular
organells.
• Removal of excess Ca2+ from the cell via energy-dependent Ca2+
pumps found on Plasma membrane.
* compartmentalize meaning : to separate something into parts and
not allow those parts to mix together.
Removal of Ca2+ stimulus

35. Table 3:
Causes and Clinical sequences of Hypocalcemia and Hypercalcemia
Clinical sequencesCauses
•Fatigue
•Neuromuscular
irritability (tetany ..)
•Cardiomyopathy
•Seizures
•Hypoparathyroidism
•Inadequate vitamin D production
• PTH resistance ( Mg deficiency)
•Acute critical illnessHypocalcemia
•Fatigue
•Vomiting
•Hyprcaciuria .. Kidny
stones
•Constapation
•Abdominal pain
•Hayperabsorption of Ca2+
•Decrease urinary excretion
• increased bone resorption .
•Idiopathic hypercalcemiaHypercalcemia

36. Calcium excretion
• 140 mgday of Ca2+ enter the intestinal lumen in digestive
secretion .
• 29% of this is reabsorbed .
• Only 100-240 mgday. By urine .
• 1-2.5% of Ca2+ filtered by the kidney.

37. Adequate intake
For men/women:
• 19-50 years : 1000 mg/day
• <50 years : 1200 mg/day
• 1500 mg/day for women not treated with estrogen ,
“ because its influences bone mineralization “

38. Calcium deficiency
• Tetany “ fail muscle contraction”
• Rickets : in children .
• Osreoporosis “ loss of bone mass” .
https://www.orthobullets.com/basic-
science/9031/ricketshttp://qpilates.net.au/osteoporosis-pilates/ access at 8-3-2018
Rickets

39. Should increased need of Ca2+ :
• High phytate diets
• Fat malabsorption
• Immobilization
• Decreased gastrointestinal transit time
• Use of thiazide diuretics (long time)

40. Excess Calcium Supplementation
• usually does not result in hypercalcemia, but may cause
mineral imbalances by :
Interfering with the absorption of other minerals, such as iron,
magnesium, and zinc.

41. Toxicity
• Upper intake : 2500 mg/day
• Hypercalcemia
• Constipation
• Kidney stones
• Deposition of ca in soft tissue
https://step1.medbullets.com/msk/112035/gout 8-3-2018
http://faressaad.com/blog/2017/06/beirut-residents-getting-much-
calcium/ access at 8-3-2018

42. Assessment
• Difficult to assess : same indicators of Vitamin D
status , bone disease , hormonal imbalance.
methods :
• presence of normal [albumin]
• CT scans
• DEXA : the best “ change in mass over time”

43. References :
1- (6th ed.) Gropper, S. A. S., Smith, J. L., & Groff, J. L. (2009). Advanced nutrition and human
metabolism.
2- Stipanuk, M. H. (2006). Biochemical, physiological, & molecular aspects of human nutrition.
St. Louis: Saunders Elsevier.