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Chemistry

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Also known as: Dl-malic acid, 6915-15-7, 2-hydroxybutanedioic acid, 2-hydroxysuccinic acid, 617-48-1, Malate
Molecular Formula
C4H6O5
Molecular Weight
134.09  g/mol
InChI Key
BJEPYKJPYRNKOW-UHFFFAOYSA-N
FDA UNII
817L1N4CKP

Malic Acid
Malic acid is a metabolite found in the aging mouse brain.
1 2D Structure

Malic Acid

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-hydroxybutanedioic acid
2.1.2 InChI
InChI=1S/C4H6O5/c5-2(4(8)9)1-3(6)7/h2,5H,1H2,(H,6,7)(H,8,9)
2.1.3 InChI Key
BJEPYKJPYRNKOW-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C(C(C(=O)O)O)C(=O)O
2.2 Other Identifiers
2.2.1 UNII
817L1N4CKP
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Calcium (hydroxy-1-malate) Hexahydrate

2. Malate

3. Malic Acid, (r)-isomer

4. Malic Acid, Calcium Salt, (1:1), (s)-isomer

5. Malic Acid, Disodium Salt

6. Malic Acid, Disodium Salt, (r)-isomer

7. Malic Acid, Disodium Salt, (s)-isomer

8. Malic Acid, Magnesium Salt (2:1)

9. Malic Acid, Monopotassium Salt, (+-)-isomer

10. Malic Acid, Potassium Salt, (r)-isomer

11. Malic Acid, Sodium Salt, (+-)-isomer

2.3.2 Depositor-Supplied Synonyms

1. Dl-malic Acid

2. 6915-15-7

3. 2-hydroxybutanedioic Acid

4. 2-hydroxysuccinic Acid

5. 617-48-1

6. Malate

7. Butanedioic Acid, Hydroxy-

8. Hydroxysuccinic Acid

9. Malic Acid, Dl-

10. Kyselina Jablecna

11. Hydroxybutanedioic Acid

12. Pomalus Acid

13. Deoxytetraric Acid

14. Dl-hydroxybutanedioic Acid

15. Hydroxybutandisaeure

16. Alpha-hydroxysuccinic Acid

17. Musashi-no-ringosan

18. Caswell No. 537

19. Dl-2-hydroxybutanedioic Acid

20. Fda 2018

21. Monohydroxybernsteinsaeure

22. Succinic Acid, Hydroxy-

23. R,s(+-)-malic Acid

24. Kyselina Jablecna [czech]

25. Malic Acid [nf]

26. Fema No. 2655

27. 2-hydroxyethane-1,2-dicarboxylic Acid

28. Pomalous Acid

29. Kyselina Hydroxybutandiova [czech]

30. D,l-malic Acid

31. Epa Pesticide Chemical Code 051101

32. Ai3-06292

33. (+/-)-malic Acid

34. Malic Acid, L-

35. Nsc-25941

36. E296

37. Butanedioic Acid, Hydroxy-, (s)-

38. Mls000084707

39. 817l1n4ckp

40. Chebi:6650

41. Ins No.296

42. (+-)-1-hydroxy-1,2-ethanedicarboxylic Acid

43. Ins No. 296

44. Ins-296

45. Nsc25941

46. Malic Acid (nf)

47. Smr000019054

48. Dl-apple Acid

49. E-296

50. Dsstox_cid_7640

51. (r)-hydroxybutanedioic Acid

52. (s)-hydroxybutanedioic Acid

53. Dsstox_rid_78538

54. Dsstox_gsid_27640

55. (+-)-malic Acid

56. R-malic Acid

57. Malicum Acidum

58. Fema Number 2655

59. Butanedioic Acid, 2-hydroxy-, (2s)-

60. Cas-6915-15-7

61. Ccris 2950

62. Ccris 6567

63. L-(-)-malicacid

64. Hsdb 1202

65. Dl-hydroxysuccinic Acid

66. Kyselina Hydroxybutandiova

67. Einecs 210-514-9

68. Einecs 230-022-8

69. Nsc 25941

70. Hydroxybutanedioic Acid, (-)-

71. (+-)-hydroxysuccinic Acid

72. Unii-817l1n4ckp

73. Aepfelsaeure

74. Nsc 9232

75. Mfcd00004245

76. Mfcd00064213

77. (+/-)-2-hydroxysuccinic Acid

78. Hydroxybutanedioic Acid, (+-)-

79. H2mal

80. Racemic Malic Acid

81. Mfcd00064212

82. .+-.-malic Acid

83. 143435-96-5

84. Opera_id_805

85. 2-hydroxyl-succinic Acid

86. Dl-malic Acid, 99%

87. Malic Acid [ii]

88. Malic Acid [mi]

89. Malic Acid,(dl)

90. 2-hydroxydicarboxylic Acid

91. Malic Acid [fcc]

92. Schembl856

93. 2-hydroxy-butanedioic Acid

94. Bmse000046

95. Bmse000904

96. Malic Acid [inci]

97. Ec 210-514-9

98. Ec 230-022-8

99. Malic Acid [vandf]

100. Malic Acid-, (l-form)-

101. Dl-malic Acid, >=99%

102. Hyoscyaminehydrobromide

103. Oprea1_130558

104. Oprea1_624131

105. Malic Acid [usp-rs]

106. Malic Acid [who-dd]

107. Butanedioic Acid, 2-hydroxy-

108. Dl-malic Acid-2-[13c]

109. Dl-hydroxysucoinic Acid

110. Butanedioic Acid, (.+-.)-

111. Dl(+/-)-malic Acid

112. Gtpl2480

113. 2-hydroxy-succinic Acid

114. Dl-hyroxybutanedioic Acid

115. Chembl1455497

116. Dtxsid0027640

117. Bdbm92495

118. Malic Acid [ep Monograph]

119. Malic Acid [usp Impurity]

120. Dl-malic Acid, Fcc, >=99%

121. Hms2358h06

122. Hms3371c13

123. Dl-malic Acid, Analytical Standard

124. Hy-y1311

125. Str03457

126. (+/-)-hydroxysuccinic Acid

127. Tox21_201536

128. Tox21_300372

129. S9001

130. Stl283959

131. Hydroxybutanedioic Acid [hsdb]

132. Akos000120085

133. Akos017278471

134. (+/-)-hydroxybutanedioic Acid

135. Am81418

136. Ccg-266122

137. Db12751

138. Dl-malic Acid, Reagentplus(r), 99%

139. Ncgc00043225-02

140. Ncgc00043225-03

141. Ncgc00254259-01

142. Ncgc00259086-01

143. Dl-malic Acid, >=98% (capillary Gc)

144. Hydroxybutanedioic Acid, (+/-)-

145. Sy003313

146. Sy009804

147. Dl-malic Acid, Reagentplus(r), >=99%

148. Db-016133

149. Dl-malic Acid 1000 Microg/ml In Methanol

150. Dl-malic Acid, Usp, 99.0-100.5%

151. Cs-0017784

152. E 296

153. Eu-0067046

154. Ft-0605225

155. Ft-0625484

156. Ft-0625485

157. Ft-0625539

158. Ft-0632189

159. M0020

160. Dl-malic Acid, Saj First Grade, >=99.0%

161. A19426

162. C00711

163. C03668

164. D04843

165. Dl-malic Acid 1000 Microg/ml In Acetonitrile

166. Dl-malic Acid, Vetec(tm) Reagent Grade, 98%

167. M-0825

168. Ab00443952-12

169. Malic Acid, Meets Usp/nf Testing Specifications

170. 4-ethoxyphenyltrans-4-propylcyclohexanecarboxylate

171. L023999

172. Q190143

173. Q-201028

174. 0c9a2dc0-fea2-4864-b98b-0597cdd0ad06

175. F0918-0088

176. Z940713496

177. Malic Acid, United States Pharmacopeia (usp) Reference Standard

178. Malic Acid (constituent Of Cranberry Liquid Preparation) [dsc]

179. Malic Acid, Pharmaceutical Secondary Standard; Certified Reference Material

180. Dl-malic Acid, Meets Analytical Specification Of Fcc, E296, 99-100.5% (alkalimetric)

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 134.09 g/mol
Molecular Formula C4H6O5
XLogP3-1.3
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count5
Rotatable Bond Count3
Exact Mass134.02152329 g/mol
Monoisotopic Mass134.02152329 g/mol
Topological Polar Surface Area94.8 Ų
Heavy Atom Count9
Formal Charge0
Complexity129
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

EXPL THER An efficcacy and safety test of a tablet containing 200 mg malic acid (and 50 mg magnesium) was conducted using patients with primary fibromyalgia syndrome. In the first part of the test, 24 patients were given three tablets twice daily (bid) for 4 weeks. In the second part, 16 patients started with three tablets bid and increased the dosage every 3 to 5 days as necessary; at month 6, the average dose was 8.8 tablets per day. (For a 50-kg person, ingestion of six tablets would be equivalent to 24 mg of malate/kg of body weight). In the first part of the study, one test patient reported diarrhea, one reported nausea, and one reported dyspepsia. (In the placebo group, two patients reported diarrhea and one reported dyspepsia.) In the second part of the study, five test patients reported diarrhea, one reported nausea, one reported dyspepsia, one reported panic attacks, and one reported dizziness.

Fuime MZ; Int J Toxicol 20 (Suppl 1): 47-55 (2001)


EXPL THER Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-alpha, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease. /L-Malic Acid/

PMID:23737849 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666396 Tang X et al; Evid Based Complement Alternat Med. (2013) Published online 2013 May 14. doi: 10.1155/2013/820695


EXPL THER Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student's T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva.

Gomez-Moreno G et al; Med Oral Patol Oral Cir Bucal. 18 (1): e49-e55 (2013)


Fourteen patients, 11 males and 3 females, with various forms of ichthyosiformdermatoses were used to evaluate the therapeutic potential of more than 60 chemicals, including malic acid. Malic acid was dissolved in either water or ethanol and incorporated into a hydrophilic ointment of plain petrolatum. The ointment, containing 5% malic acid (pH not specified), was applied twice daily to the appropriate test site for 2 weeks. Daily to weekly observations were made. Malic acid provided 3+ (disappearance of scales from lesions) or 4+ (restoration to normal looking skin) improvement in all patients except one with epidermolytic hyperkeratosis.

Fuime MZ; Int J Toxicol 20 (Suppl 1): 47-55 (2001)


5 Pharmacology and Biochemistry
5.1 Absorption, Distribution and Excretion

Upon oral and IP administration of radioactive malic acid to rats, most of the radioactivity was excreted as carbon dioxide.

Fuime MZ; Int J Toxicol 20 (Suppl 1): 47-55 (2001)


5.2 Metabolism/Metabolites

Acidulents. Like l-(14)C4 malic acid, dl-(14)C4 malic acid, when admin ip or orally to rats was extensively metabolized; 90-95% of (14)C was excreted through lungs as (14)CO2. ... Metabolized at same rate irrespective of route admin ... . /L- & dl-malic acid/

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 246


Malic acid is an intermediate in the citric acid cycle. It is formed from fumaric acid and is oxidized to oxaloacetic acid. It is also metabolized to pyruvic acid by malic enzyme which is present in many biologic systems, including bacteria and plants. L-Malic and dl-malic acid are both rapidly metabolized in the rat. Orally or ip administered l- or dl-malic acid was extensively eliminated as carbon dioxide (83 to 92%). No differences between the two forms were found in the rates (90 to 95% in 24 hr) or routes of excretion.

Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4942


Malates are normal constituents of the diet of humans and animals and, when ingested, are rapidly and completely metabolized to CO2. /Malates/

EFSA Journal 12 (2): 3563 (2014)


... Both enantiomers of malic acid are readily metabolised by laboratory animals and humans and that there was no reason to distinguish between L-malic acid and DL-malic acid when considering their safe use in food.

EFSA Journal 12 (2): 3563 (2014)


Upon oral and IP administration of radioactive Malic Acid to rats, most of the radioactivity was excreted as carbon dioxide.

Fuime MZ; Int J Toxicol 20 (Suppl 1): 47-55 (2001)


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","supplierCountry":"CHINA","foreign_port":"XINGANG (CHINA)","customer":"CITRUS.INDIA","customerCountry":"INDIA","quantity":"22000.00","actualQuantity":"22000","unit":"KGS","unitRateFc":"1.4","totalValueFC":"31993.1","currency":"USD","unitRateINR":"120.8","date":"07-Jul-2024","totalValueINR":"2656797","totalValueInUsd":"31993.1","indian_port":"JNPT","hs_no":"29181990","bill_no":"4378762","productDescription":"API","marketType":"REGULATED MARKET","country":"CHINA","selfForZScoreResived":"Pharma Grade","supplierPort":"XINGANG (CHINA)","supplierAddress":"CORPORATE SERVICES CENTRE, SUITE 23, 1ST FLOOR, EDEN PLAZA, EDEN ISLAND, MAHE, REPUBLIC OF SEYCHELLES ., Seychelles","customerAddress":"BHAWAN KUND"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1720722600,"product":"L-MALIC ACID","address":"N - 216 N-217, M. I. D. 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SHUNYU BUILDING, 19 BAILONGJIANG EAST STREET, JIANYE DISTRICT, NANJING 210019 China","customerAddress":"1726\/205, RITCO RICE PALACE"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1722018600,"product":"L-MALIC ACID","address":"12 6 214 A1 SHILPA HOUSE HYDERABAD ROAD","city":"RAICHUR","supplier":"HEFEI HOME SUNSHINE ","supplierCountry":"CHINA","foreign_port":"BEIJING","customer":"SHILPA PHARMA LIFESCIENCES LIMITED","customerCountry":"INDIA","quantity":"25.00","actualQuantity":"25","unit":"KGS","unitRateFc":"18","totalValueFC":"458.2","currency":"USD","unitRateINR":"1521.9","date":"27-Jul-2024","totalValueINR":"38047.5","totalValueInUsd":"458.2","indian_port":"Madras Air","hs_no":"29181990","bill_no":"4724092","productDescription":"API","marketType":"REGULATED MARKET","country":"CHINA","selfForZScoreResived":"Pharma Grade","supplierPort":"BEIJING","supplierAddress":"Co.,Ltd., Add: 1002, HuanmaoBuilding, No.105,Mengcheng RoadHefei City, 230061, CHINA CN","customerAddress":"12 6 214 A1 SHILPA HOUSE HYDERABAD ROAD"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1722450600,"product":"MALIC ACID GRANULAR 19042 SAP NO-180000140 ( NOT FOR MEDICINAL USE)","address":"3B, DLF CORPORATE PARK, S-BLOCK,","city":"GURGAON","supplier":"ISEGEN SOUTH AFRICA ","supplierCountry":"SOUTH AFRICA","foreign_port":"DURBAN","customer":"PEPSICO INDIA HOLDINGS ","customerCountry":"INDIA","quantity":"20000.00","actualQuantity":"20","unit":"MTS","unitRateFc":"2475","totalValueFC":"50398.5","currency":"USD","unitRateINR":"209261.3","date":"01-Aug-2024","totalValueINR":"4185225","totalValueInUsd":"50398.5","indian_port":"GRFL ICD\/SAHNEWAL","hs_no":"29181990","bill_no":"4811020","productDescription":"API","marketType":"LESS REGULATED MARKET","country":"SOUTH AFRICA","selfForZScoreResived":"Non Pharma","supplierPort":"DURBAN","supplierAddress":"284 REFINERY ROAD, ISIPINGOBEACH, 4133SDNF SOUTH AFRICA","customerAddress":"3B, DLF CORPORATE PARK, S-BLOCK,"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1722969000,"product":"DL-MALIC ACID EMPROVE ESSENTIAL PH EUR,NF,FCC,E 296 7PCS X25KG","address":"50A , RING ROAD,","city":"BANGALORE, KARNATAKA","supplier":"MERCK LIFE SCIENCE KGAA","supplierCountry":"GERMANY","foreign_port":"FRANKFURT\/MAIN INT\\'L","customer":"MERCK GROUP","customerCountry":"INDIA","quantity":"175.00","actualQuantity":"175","unit":"KGS","unitRateFc":"2430.8","totalValueFC":"5135.4","currency":"INR","unitRateINR":"2436.9","date":"07-Aug-2024","totalValueINR":"426456.07","totalValueInUsd":"5135.4","indian_port":"Bombay Air","hs_no":"29181990","bill_no":"4931260","productDescription":"API","marketType":"REGULATED MARKET","country":"GERMANY","selfForZScoreResived":"Pharma Grade","supplierPort":"FRANKFURT\/MAIN INT\\'L","supplierAddress":"Frankfurter Strasse 25064293 Darmstadt Germany (BENEFICIARY MERCKFINANCIAL SERVICES GMBH) GERMANY","customerAddress":"50A , RING ROAD,"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1723833000,"product":"L-MALIC ACID","address":"ALKEM HOUSE, DEVASHISH ADJACENT TO","city":"LOWER PAREL, MUMBAI. 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18-Jan-2021
26-Aug-2024
KGS
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