Chemical Properties
White or nearly white, crystalline powder or granules having a
slight odor and a strongly acidic taste. It is hygroscopic. The
synthetic material produced commercially in Europe and the USA is
a racemic mixture, whereas the naturally occurring material found
in apples and many other fruits and plants is levorotatory.
Chemical Properties
White to nearly white crystals or crystal powder
Definition
A
colorless crystalline carboxylic acid that is
found in unripe fruits. It tastes of apples
and is used in food flavorings.
Definition
ChEBI: A 2-hydroxydicarboxylic acid that is succinic acid in which one of the hydrogens attached to a carbon is replaced by a hydroxy group.
Production Methods
Malic acid is manufactured by hydrating maleic and fumaric acids
in the presence of suitable catalysts. The malic acid formed is then
separated from the equilibrium product mixture.
Biotechnological Production
DL-malic acid as well as L-malic acid can be used in beverage, food, and animal
nutrition. DL-malic acid is mainly derived from chemical synthesis, whereas L-malic
acid is produced biotechnologically by enzymatic or fermentative processes.
Fumaric acid can be converted to L-malic acid using fumarases. Different
microorganisms (e.g. Brevibacterium flavum, Brevibacterum ammoniagenes, and
Corynebacterium species) are able to form naturally high amounts of fumarase
intracellularly. For example, B. flavum has been immobilized in j-carrageenan
and polyethyleneimine for whole-cell biocatalysis. A fumarase activity of
2.16 mmol.ml(gel)-1.h -1 at 55 C has been reported. This process has been
used to produce 30 metric tons of L-malic acid per month in a continuous process
with a 1,000 L column fed at a flow rate of 450 L.h-1 of 1 M sodium fumarate
solution. Genetic engineering has been used to improve productivity, by
which S. cerevisiae is modified to overexpress fumarase. With this method, a
conversion rate of 65 mmol.g-1.h -1 has been observed.
Another possibility is the cultivation of an L-malic acid forming microorganism
(e.g. Aspergillus flavus or Schizophyllum commune). The best results have
been achieved by cultivation of A. flavus on glucose.Afinal product concentration of
113 g.L-1 with a yield of 1.26 mol of malic acid per mole of glucose and a productivity
of 0.59 g.L-1.h-1 has been measured. Moreover, new biotechnological
routes have been described using metabolically engineered S. cereviciae. In batch
cultivations, concentrations up to 59 g.L-1 with a yield of 0.42 mol of malic acid per
mole of glucose and a productivity of 0.19 g.L-1.h-1 have been observed.
General Description
The chiral resolution of DL-malic acid by ligand-exchange capillary electrophoresis was studied.
Flammability and Explosibility
Nonflammable
Pharmaceutical Applications
Malic acid is used in pharmaceutical formulations as a generalpurpose
acidulant. It possesses a slight apple flavor and is used as a
flavoring agent to mask bitter tastes and provide tartness. Malic
acid is also used as an alternative to citric acid in effervescent
powders, mouthwashes, and tooth-cleaning tablets.
In addition, malic acid has chelating and antioxidant properties.
It may be used with butylated hydroxytoluene as a synergist in order
to retard oxidation in vegetable oils. In food products it may be used
in concentrations up to 420 ppm.
Therapeutically, malic acid has been used topically in combination
with benzoic acid and salicylic acid to treat burns, ulcers, and
wounds. It has also been used orally and parenterally, either
intravenously or intramuscularly, in the treatment of liver disorders,
and as a sialagogue.
Biochem/physiol Actions
Malic acid is a dicarboxylic acid and an important regulatory metabolite. It has been implicated in process of fruit ripening. Malic acid is important for the starch metabolism; low malic acid content results in transient accumulation of starch. Mitochondrial-malate metabolism modulates ADP-glucose pyrophosphorylase activity and redox status of plastids.
Mechanism of action
Malic acid is absorbed from the gastrointestinal tract from whence it is transported via the portal circulation to the liver. There are a few enzymes that metabolize malic acid. Malic enzyme catalyzes the oxidative decarboxylation of L-malate to pyruvate with concomitant reduction of the cofactor NAD+ (oxidized form of nicotinamide adenine dinucleotide) or NADP+ (oxidized form of nicotinamide adenine dinucleotide phosphate). These reactions require the divalent cations magnesium or manganese. Three isoforms of malic enzyme have been identified in mammals: a cytosolic NADP+-dependent malic enzyme, a mitochondrial NADP+- dependent malic enzyme and a mitochondrial NAD(P)+-dependent malic enzyme. The latter can use either NAD+ or NADP+ as the cofactor but prefers NAD+. Pyruvate formed from malate can itself be metabolized in a number of ways, including metabolism via a number of metabolic steps to glucose. Malate can also be metabolized to oxaloacetate via the citric acid cycle. The mitochondrial malic enzyme, particularly in brain cells may play a key role in the pyruvate recycling pathway, which utilizes dicarboxylic acids and substrates, such as glutamine, to provide pyruvate to maintain the citric acid cycle activity when glucose and lactate are low.
Safety
Malic acid is used in oral, topical, and parenteral pharmaceutical
formulations in addition to food products, and is generally regarded
as a relatively nontoxic and nonirritant material. However,
concentrated solutions may be irritant.
LD50 (rat, oral): 1.6 g/kg(3)
LD50 (rat, IP): 0.1 g/kg
storage
Malic acid is stable at temperatures up to 150°C. At temperatures
above 150°C it begins to lose water very slowly to yield fumaric
acid; complete decomposition occurs at about 180°C to give
fumaric acid and maleic anhydride.
Malic acid is readily degraded by many aerobic and anaerobic
microorganisms. Conditions of high humidity and elevated
temperatures should be avoided to prevent caking.
The effects of grinding and humidity on malic acid have also
been investigated.
The bulk material should be stored in a well-closed container, in
a cool, dry place.
Purification Methods
Crystallise the acid from acetone, then from acetone/CCl4, or from ethyl acetate by adding pet ether (b 60-70o). Dry it at 35o under 1mm pressure to avoid formation of the anhydride. [Beilstein 3 IV 1124.]
Incompatibilities
Malic acid can react with oxidizing materials. Aqueous solutions
are mildly corrosive to carbon steels.
Toxics Screening Level
The initial threshold screening level (ITSL) for malic acid is 5 μg/m3 based on an annual
averaging time.
Regulatory Status
GRAS listed. Both the racemic mixture and the levorotatory isomer
are accepted as food additives in Europe. The DL and L forms are
included in the FDA Inactive Ingredients Database (oral preparations).
Included in nonparenteral and parenteral medicines licensed
in the UK. Included in the Canadian List of Acceptable Nonmedicinal
Ingredients.
