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Identification
Name Calcium
Accession Number DB01373
Type small molecule
Groups experimental
Description

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast.
Structure Thumb
Synonyms Not Available
Brand names Not Available
Brand name mixtures Not Available
Categories Not Available
CAS number Not Available
Weight Not Available
Chemical Formula Not Available
InChI Key Not Available
InChI Not Available
IUPAC Name Not Available
SMILES Not Available
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. It is vital in cell signaling, muscular contractions, bone health, and signalling cascades.
Pharmacodynamics Calcium (Ca2+) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.
Mechanism of action Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination The kidney excretes 250 mmol a day in urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d.
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Dental
Liquid Intravenous
Liquid Oral
Liquid Sublingual
Paste Dental
Powder Oral
Powder, for solution Oral
Solution Intramuscular
Solution Intravenous
Solution Oral
Solution / drops Oral
Syrup Oral
Tablet Oral
Tablet, chewable Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties Not Available
References
Synthesis Reference Not Available
General Reference
  1. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997 Sep 4;337(10):670-6. Pubmed
  2. Weingarten MA, Zalmanovici A, Yaphe J: Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003548. Pubmed
  3. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83. Pubmed
  4. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA: Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet. 2005 May 7-13;365(9471):1621-8. Pubmed
  5. Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ: Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ. 2005 Apr 30;330(7498):1003. Pubmed
External Links
Resource Link
ChEBI 22984 Link_out
ChEMBL 22984 Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Calcium Link_out
ATC Codes
  • D11AX03
  • V03AF04
  • C05BX01
  • B02BC08
  • B01AC08
  • R01AX01
  • N02BA15
  • V03AF03
  • G04BA03
  • B05XA07
  • A01AD11
  • A12AA03
  • A11HA31
  • V08AC10
  • A12AA11
  • D03AX04
  • A12AA06
  • A11GA01
  • J04AA03
  • A12AA12
  • A12AA30
  • A06AC08
  • A12AA02
  • A12AA05
  • A12AA09
  • N07BB02
  • A07XA03
  • A12AA07
  • A12AA10
  • V03AE01
  • A02AC01
  • A12AA04
  • A02AC02
  • A12AA08
  • A12AA01
  • A12AA20
AHFS Codes
  • 34:00.00
  • 88:29.00*
  • 56:04.00
  • 56:12.00
  • 92:02.00*
  • 40:18.17
  • 88:12.00
  • 40:18.19
  • 40:12.00
  • 88:08.00
  • 40:34.00*
PDB Entries Not Available
FDA label show (25.6 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Voltage-dependent L-type calcium channel subunit alpha-1C

Pharmacological action: yes
Actions: ligand

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the "high-voltage activated" (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds

Organism class: human
UniProt ID: Q13936 Link_out
Gene: CACNA1C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Boda D, Giri J, Henderson D, Eisenberg B, Gillespie D: Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom’s particle insertion method. J Chem Phys. 2011 Feb 7;134(5):055102. Pubmed

2. Calcium-transporting ATPase type 2C member 1

Pharmacological action: yes
Actions: agonist

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium

Organism class: human
UniProt ID: P98194 Link_out
Gene: ATP2C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Shi X, Chen M, Huvos PE, Hardwicke PM: Amino acid sequence of a Ca(2+)-transporting ATPase from the sarcoplasmic reticulum of the cross-striated part of the adductor muscle of the deep sea scallop: comparison to serca enzymes of other animals. Comp Biochem Physiol B Biochem Mol Biol. 1998 Jun;120(2):359-74. Pubmed
  2. Bonza MC, Martin H, Kang M, Lewis G, Greiner T, Giacometti S, Van Etten JL, De Michelis MI, Thiel G, Moroni A: A functional calcium-transporting ATPase encoded by chlorella viruses. J Gen Virol. 2010 Oct;91(Pt 10):2620-9. Epub 2010 Jun 23. Pubmed

3. Troponin C, skeletal muscle

Pharmacological action: yes
Actions: agonist

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments

Organism class: human
UniProt ID: P02585 Link_out
Gene: TNNC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Martin SR, Avella G, Adrover M, de Nicola GF, Bullard B, Pastore A: Binding Properties of the Calcium-Activated F2 Isoform of Lethocerus Troponin C. Biochemistry. 2011 Feb 10. Pubmed
  2. Kreutziger KL, Piroddi N, McMichael JT, Tesi C, Poggesi C, Regnier M: Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle. J Mol Cell Cardiol. 2011 Jan;50(1):165-74. Epub 2010 Oct 28. Pubmed
  3. Robertson IM, Sun YB, Li MX, Sykes BD: A structural and functional perspective into the mechanism of Ca2+-sensitizers that target the cardiac troponin complex. J Mol Cell Cardiol. 2010 Dec;49(6):1031-41. Epub 2010 Aug 27. Pubmed
  4. Dweck D, Reynaldo DP, Pinto JR, Potter JD: A dilated cardiomyopathy troponin C mutation lowers contractile force by reducing strong myosin-actin binding. J Biol Chem. 2010 Jun 4;285(23):17371-9. Epub 2010 Apr 6. Pubmed

4. Troponin C, slow skeletal and cardiac muscles

Pharmacological action: yes
Actions: agonist

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments

Organism class: human
UniProt ID: P63316 Link_out
Gene: TNNC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dweck D, Reynaldo DP, Pinto JR, Potter JD: A dilated cardiomyopathy troponin C mutation lowers contractile force by reducing strong myosin-actin binding. J Biol Chem. 2010 Jun 4;285(23):17371-9. Epub 2010 Apr 6. Pubmed
  2. Swindle N, Tikunova SB: Hypertrophic cardiomyopathy-linked mutation D145E drastically alters calcium binding by the C-domain of cardiac troponin C. Biochemistry. 2010 Jun 15;49(23):4813-20. Pubmed
  3. Parvatiyar MS, Pinto JR, Liang J, Potter JD: Predicting cardiomyopathic phenotypes by altering Ca2+ affinity of cardiac troponin C. J Biol Chem. 2010 Sep 3;285(36):27785-97. Epub 2010 Jun 21. Pubmed
  4. Baylor SM, Hollingworth S: Calcium indicators and calcium signalling in skeletal muscle fibres during excitation-contraction coupling. Prog Biophys Mol Biol. 2010 Jun 25. Pubmed

5. Spectrin beta chain, brain 1

Pharmacological action: unknown
Actions: agonist
Organism class: human
UniProt ID: Q01082 Link_out
Gene: SPTBN1
SNPs: SNPJam Report Link_out

References:
  1. Wallis CJ, Wenegieme EF, Babitch JA: Characterization of calcium binding to brain spectrin. J Biol Chem. 1992 Mar 5;267(7):4333-7. Pubmed

6. Protein S100-B

Pharmacological action: unknown

Weakly binds calcium but binds zinc very tightly- distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase

Organism class: human
UniProt ID: P04271 Link_out
Gene: S100B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lee TS, Mane S, Eid T, Zhao H, Lin A, Guan Z, Kim JH, Schweitzer J, King-Stevens D, Weber P, Spencer SS, Spencer DD, de Lanerolle NC: Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med. 2007 Jan-Feb;13(1-2):1-13. Pubmed
  2. Marlatt NM, Shaw GS: Amide exchange shows calcium-induced conformational changes are transmitted to the dimer interface of S100B. Biochemistry. 2007 Jun 26;46(25):7478-87. Epub 2007 May 31. Pubmed
  3. Liang J, Luo G, Ning X, Shi Y, Zhai H, Sun S, Jin H, Liu Z, Zhang F, Lu Y, Zhao Y, Chen X, Zhang H, Guo X, Wu K, Fan D: Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Biochem Cell Biol. 2007 Jun;85(3):375-83. Pubmed
  4. Friel LA, Romero R, Edwin S, Nien JK, Gomez R, Chaiworapongsa T, Kusanovic JP, Tolosa JE, Hassan SS, Espinoza J: The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes. J Perinat Med. 2007;35(5):385-93. Pubmed

7. Calpastatin

Pharmacological action: unknown

Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue

Organism class: human
UniProt ID: P20810 Link_out
Gene: CAST Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hanna RA, Garcia-Diaz BE, Davies PL: Calpastatin simultaneously binds four calpains with different kinetic constants. FEBS Lett. 2007 Jun 26;581(16):2894-8. Epub 2007 May 25. Pubmed
  2. De Tullio R, Averna M, Stifanese R, Parr T, Bardsley RG, Pontremoli S, Melloni E: Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons. Arch Biochem Biophys. 2007 Sep 1;465(1):148-56. Epub 2007 May 30. Pubmed

8. Cartilage oligomeric matrix protein

Pharmacological action: unknown
Organism class: human
UniProt ID: P49747 Link_out
Gene: COMP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J: Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem. 2007 Aug 24;282(34):24591-8. Epub 2007 Jun 22. Pubmed

9. Calmodulin

Pharmacological action: unknown

Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases

Organism class: human
UniProt ID: P62158 Link_out
Gene: CALM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sosa V, Carbo R, Guarner V: Participation of glucose transporters on atrial natriuretic peptide-induced glucose uptake by adult and neonatal cardiomyocytes under oxygenation and hypoxia. Eur J Pharmacol. 2007 Jul 30;568(1-3):83-8. Epub 2007 Apr 30. Pubmed
  2. Zhou Z, Yin J, Dou Z, Tang J, Zhang C, Cao Y: The calponin homology domain of Vav1 associates with calmodulin and is prerequisite to T cell antigen receptor-induced calcium release in Jurkat T lymphocytes. J Biol Chem. 2007 Aug 10;282(32):23737-44. Epub 2007 Jun 5. Pubmed
  3. Schallreuter KU, Gibbons NC, Zothner C, Abou Elloof MM, Wood JM: Hydrogen peroxide-mediated oxidative stress disrupts calcium binding on calmodulin: more evidence for oxidative stress in vitiligo. Biochem Biophys Res Commun. 2007 Aug 17;360(1):70-5. Epub 2007 Jun 11. Pubmed
  4. Caride AJ, Filoteo AG, Penniston JT, Strehler EE: The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics: implications for Ca2+ signaling. J Biol Chem. 2007 Aug 31;282(35):25640-8. Epub 2007 Jun 26. Pubmed
  5. Lo LW, Chen YC, Chen YJ, Wongcharoen W, Lin CI, Chen SA: Calmodulin kinase II inhibition prevents arrhythmic activity induced by alpha and beta adrenergic agonists in rabbit pulmonary veins. Eur J Pharmacol. 2007 Oct 1;571(2-3):197-208. Epub 2007 Jun 13. Pubmed
Comments
Drug created on July 06, 2007 14:28 / Updated on April 19, 2011 15:10

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.