Fumarase Deficiency: Causes, Symptoms, Diagnosis and Treatment

Fumarase Deficiency 1
FUMARASE DEFICIENCY
(Student Name)
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Fumarase Deficiency 2
Fumarase Deficiency
Overview
Fumarase deficiency is also referred to as Fumarate hydratase insufficiency or Fumaric aciduria.
The disorder is classified into the categories of Genetic and Congenital illnesses, Nervous system
infections and metabolic disorders (3). The disease affects a person’s mitochondrial metabolism.
The deficiency in the fumarase is as a result of fumarate hydratase catalyst impairment. The
succinate shortage in dehydrogenase distresses the mitochondrial composite II which joins the
electron conveyance chain with the TCA cycle (4). Therefore, the protein biochemical pathway
is affected by the infection; the influenced protein is Fumarate hydratase class II. Fumarase
insufficiency leads to Leigh syndrome, mental and cardiomyopathy sicknesses, motor skill
weakening and leukodystrophy. The scarcity of alpha-ketoglutarate of the dehydrogenase results
in hyperlactatemia and encephalopathy and even death in children (12).
Fumarase scarcity is instigated by the mutation present in the gene of fumarate
hydrogenase (FH). The genomic factor codes the enzymatic substances that translate fumarate to
malate within the mitochondrion. Therefore, transmutations in the genetic material obstruct the
functioning of the enzyme (9). Energy production is vital to the body cells especially during the
development of the brain. Thus, when the proteins fail to work efficiently, there is a problem in
the growth of an individual’s brain (13). This leads to several symptoms and signs of fumarase
inadequacy. The TCA pathway involves the Fumaric Hydratase class II (FumC) gene which is
usually a backup for FumA during the oxidative stress and iron limitation circumstances (7).
Another name (s): fumarase; L-malate hydro-lyase; (S)-malate hydro-lyase
Systematic name: (S)-malate hydro-lyase (fumarate-forming)

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The metabolic manipulator of fumarase shortage is fumarate hydratase, whose other
names are (S)-malate hydro-lyase, L-malate hydro-lyase, or fumarase. The enzyme assignment
number is of the manipulator is EC: 4.2.1.2. The TCA cycle is usually involved in the process of
FH enzyme production (1). Therefore, FumC which is said to be the backup catalyst for FumA
during the oxidative stress conditions is involved in the TCA biochemical pathways. The
enzymatic reaction consists of the conversion of fumarate substrates to L-malate (14).
Reaction: H2O +fumarate = (S)-malate
The structure of the fumarate hydrogenase manipulator
Figure 1: The structure comprises of two sites for substrate-binding which are the non-
enzymatic B site and the enzymatic site A. The locations are essential in the transportation of
products or substrates between the solvent and the active spot. The B site also links the effectors
of the allosteric substitutes (12).
Source; Bardella et al. (1)
The process is regulated by S-2,3-dicarboxyaziridine, ATP and citrate.

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The TCA cycle
Figure 2: Notes: the TCA pathway consists of a procedure that converts fumarate to L-malate.
The reaction is catalyzed by enzymatic substitutes that are encoded by the fumarase genes. The
general catalytic action is:
CH3-CO-S-CoA + H2O + GDP + Pi = 2 CO2 + 4 x 2H + HS-CoA + GTP
Source; Briere et al. (4)