Acyl-CoA synthetase family member 3 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that in humans is encoded by the ''ACSF3''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Structure
The ACSF3 gene is located on the 16th chromosome, with its specific location being 16q24.3. The gene contains 17 exons.
ASCL4 encodes a 64.1 kDa protein that is composed of 576 amino acids; 20 peptides have been observed through mass spectrometry data.
Function
This gene encodes a member of the
acetyl—CoA synthetase
Acetyl-CoA synthetase (ACS) or Acetate—CoA ligase is an enzyme () involved in metabolism of acetate. It is in the ligase class of enzymes, meaning that it catalyzes the formation of a new chemical bond between two large molecules.
Reaction
The ...
family of enzymes that activate
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
s by catalyzing the formation of a
thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by ...
linkage between fatty acids and
coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
. The encoded protein is localized to
mitochondria, has high specificity for
malonate
The conjugate acids are in :Carboxylic acids.
{{Commons category, Carboxylate ions, Carboxylate anions
Carbon compounds
Oxyanions ...
and methylmalonate and possesses malonyl-CoA synthetase activity.
Clinical significance
Mutations in this gene have been shown to cause
combined malonic and methylmalonic aciduria
Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. Some researchers have hypothes ...
(CMAMMA).
CMAMMA is a condition characterized by high levels of
malonic acid
Malonic acid (IUPAC systematic name: propanedioic acid) is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic aci ...
and
methylmalonic acid
Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''- methylated derivative of malonate.
The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylma ...
, because deficiencies in this gene cause these metabolites to not be broken down. The disease is typically diagnosed by either genetic testing or higher levels of methylmalonic acid than malonic acid, although both are elevated. By calculating the malonic acid to methylmalonic acid ratio in blood plasma, CMAMMA can be distinguished from classic
methylmalonic acidemia
Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to prope ...
.
The disorder typically presents symptoms early in childhood, first starting with high levels of acid in the blood (
ketoacidosis
Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in ...
). The disorder can also present as involuntary muscle tensing (
dystonia), weak muscle tone (
hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...
), developmental delay, an inability to grow and gain weight at the expected rate (
failure to thrive
Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...
), low blood sugar (
hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose be ...
), and coma. Some affected children can even have
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
. Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.
References
Further reading
*
External links
*
EC 6.2.1
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