Fructose-1, 6-Bis-Phosphatase- Deficiency and Health Impact

This article discusses Fructose-1, 6-Bis-Phosphatase- Deficiency, an inherited metabolic disorder that leads to hypoglycemia and metabolic acidosis. It covers the structure of the enzyme, intracellular metabolic pathways, disorders, treatment, and relevant policies. The article concludes that avoiding fructose and similar sugar intakes aid in combating the enzyme deficiency syndrome.

Running Head: FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH
IMPACT
Fructose-1, 6-bisPhosphatase- Deficiency and health impact
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1FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH IMPACT
Introduction:
Fructose-1, 6-bisphosphatase is an enzyme that has EC number 3.1.3.11. This enzyme
converts fructose-1, 6-bisphosphate to fructose-6-phosphate in the gluconeogenesis as well as
the Calvin cycle [1]. Both of this metabolic pathways are anabolic in nature that aids in the
building of molecules from smaller units. This is a type of hydrolases enzyme. It specifically
acts as a phosphoric monoester hydrolases that acts on the ester bonds [2] [1].
Discussion:
Structure of the enzyme: The enzyme has a structure that is similar to that of the inositol-
5-phosphate. It consists of a structurally conserved family that is exploited in diverse
metabolic pathways. It contains a motif that binds to metal ions to promote the catalysis
reaction [3].
Fig1: The biochemical reaction catalysed by the enzyme [2]
Intracellular metabolic biochemical pathways that is affected: It acts as a rate limiting
enzyme in gluconeogenesis. It has an important role in the regulation of the glucose sensing
as well as the insulin secretion of the beta cells of the pancreas. It also modulates the glycerol
level in gluconeogenesis in the liver. This hydrolase enzyme is an important regulator of the
adiposity as well as the appetite [2]. Elevated levels of the enzyme in the liver after excessive

2FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH IMPACT
intake of the nutrient induces the secretion of elevated levels of satiety hormone that causes
reduction of the appetite stimulating neuropeptides hence promoting a feedback mechanism
for weight gain. It acts in the rate limiting step for conversion of the fructose-1, 6-
bisphosphate to fructose-6-phosphate, and acts in the presence of a divalent cation [4] [10].
The relevant transport, half-life, receptor activation and fate: The expression of the FBP1
gene produces Fructose-1, 6-bisphosphatase. It is a protein coding gene. The cytogenetic
location of the gene is 9q22.32 that is the long arm of the chromosome 9 at the position 22.32
[5]. The Fructose-1, 6-bisphosphatase enzyme is stimulated by adenosine triphosphate (ATP)
and inhibited by adenosine monophosphate (AMP).
Disorders related to malfunction of the above: Fructose-1, 6-bisphosphatase deficiency is a
metabolic disorder which is inherited and due to this deficiency the body is unable to make
glucose. Untreated metabolic disorder related to the deficiency of the enzyme leads to
hypoglycemia and metabolic acidosis if the individual is fasting, there can be episodes of
hyperventilation, apnoea also known as suspension of breathing and ketosis [5]. The
inheritance of the deficiency is in an autosomal recessive manner. Other symptoms of the
deficiency includes diarrhoea and hyperuricemia that is characterised by elevated levels of
uric acid in the blood [4] [11].

3FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH IMPACT
Fig 2: The deficiency of the Fructose-1, 6-bisphosphatase
The biochemistry behind this is that since there is low level of glucose circulating in the
blood the body utilises the stored glucose that is stored in the liver in the form of glycerol.
Utilisation of the reserved glucose causes serious depletion of the sugar level in the body and
the urgency of aiding to restore the normal levels is highly required [6]. The low level of
blood glucose is due to the impaired gluconeogenesis cycle in which the conversion of
fructose-1, 6-bisphosphate to fructose-6-phosphate is impaired hence the fructose-6-
phosphate that is not formed cannot form the glucose-6-phosphate that aids in formation of
glucose. This aids to the low blood glucose level in an individual with Fructose-1, 6-
bisphosphatase deficiency [7].
Treatment: The deficiency of this enzyme Fructose-1, 6-bisphosphatase can be treated by
complete avoidance of fructose and the related sugars. Prolonged fasting sessions should be

4FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH IMPACT
avoided. If this is maintained no other specific treatment is required for the treatment of this
deficiency unless the deficiency is chronic [7] [9].
Relevant policies pertinent to the disorder: The Australian National Diabetes Strategy has
the goals to outline the national response of Australia to diabetes and also educate how
existing limited health care responses can be exploited at all levels of the government by
efficient coordination. This strategy identifies the most efficacious and appropriate
interventions to combat glucose impairment among the people [8]. The policy majorly
involves educating and spreading the awareness plan in the family of the affected individual,
the blood sugar level should be regularly monitored of the affected individual at regular
intervals and if the glucose level in the blood has reduced a lot then administration of
glucagon should be encouraged.
Conclusion:
It can be concluded from this above article that fructose-1, 6-bisphosphatase is a very
essential enzyme for regulating the blood glucose level and the prevention of the metabolic
acidosis that also occurs as a consequence. Prevention of long hours of fasting and avoiding
fructose and similar sugar intakes aid in combating the enzyme deficiency syndrome that is
characterised by hypoglycemia and metabolic acidosis.

5FRUCTOSE-1, 6-BIS-PHOSPHATASE- DEFICIENCY AND HEALTH IMPACT
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