Hereditary Fructose Intolerance: Reasons for Inability to Metabolize Fructose

This article explains the reasons why a person suffering from Hereditary Fructose Intolerance is not able to metabolize fructose. It also discusses the process of fructose metabolism and the effects of mutations on genes. The article provides insights into the symptoms of HFI disorder and the treatment options available.

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NUTRITIONAL BIOCHEMISTRY
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Reasons why a person suffering from Hereditary Fructose Intolerance is not able to
metabolize fructose
Hereditary fructose intolerance is a disease caused by the deficiency of aldolase B
enzyme. A person suffering from HFI should not ingest fructose nor sucrose as this may lead to a
severe disease called hypoglycemia and also the build-up of other dangerous substances in the
liver. According to Bouteldia & Timson1, Mutations in the ALDOB gene cause this condition.
These genes are inherited in a recessive manner. The gene also provides the directives for
making the aldolase B enzyme. The enzyme is located in the liver and helps in fructose
breakdown into energy. The alterations of ALDOB gene then reduce the capability of aldolase B
enzyme to metabolize fructose.
Fructose digestion starts in the small intestines and because the body cannot absorb solid
molecules then it is broken down into fructose and sucrose particles by sucrose enzyme. Fructose
molecules then enter the small intestines lining through a channel into the bloodstream.
Bouteldia & Timson1 also explained that after fructose enters the bloodstream, it then travels
with all the other absorbed nutrients for metabolism in the liber. Metabolism then occurs in the
liver. The process of metabolism of fructose in the liver is called fructolysis.
Fructose metabolism is started by its phosphorylation in the liver to D-fructose 1-
phosphate. This is characterized via an enzyme called fructokinase. According to
Goudsmit2 ,when there is the deficiency aldolase, D-fructose 1-phosphate accumulates in the
liver and therefore inhibiting a kinase reaction. This results in a slower removal of fructose in the
bloodstream. Goudsmit2 also explained that fructose may be phosphorylated in the muscle or as
adipose tissue when their concentration goes high.2 This is done by an enzyme called

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hexokinase. D-fructose 6-phosphate produced then enters the catabolic pathways or can be
changed to glycogen. To avoid hypoglycemia, it’s therefore released into the blood.
Human liver aldolase works together with D-fructose 1-phosphate and D-fructose 1, 6-
biphosphate substrates. Patients with hereditary fructose intolerance indicate a significant
functioning of fructose 1,6-biphosphate than the fructose 1-phosphate in the liver tissues. There
is also the increase in enzyme elevation due to ingestion of D-fructose. Liver cirrhosis and
fibrosis are some of the chronic diseases that are accompanied by hereditary fructose disorder.
There are histologic changes from 1 to 1.5h in the liver hepatocytes after fructose ingestion. The
amount of AST and GPT released then increases.
Parents of individuals with hereditary fructose intolerance disease carry a copy of the
mutated gene. According to Lenaspa et al3, there are several symptoms of HFI disorder, for
example, poor feeding in case the patient is a baby, vomiting, convulsions, excessive sleepiness,
avoidance of fruits, irritability, and prolonged jaundice. Continuous ingestion of fructose-
containing fruits may lead to the damage of the kidney and liver. When the infants are affected,
they fail to gain weight and grow. It also may lead to low blood sugar. The liver of the affected
may also enlarge. Lenaspa et al3 reported that continuous exposure to fructose may lead to coma
and death due to kidney and liver failures. Symptoms vary from one person to another.
According to coffee4, eliminating fructose and sucrose from the diet helps in the treatment of the
disease though when severe it may not intestines in treating the liver disease. Therefore, a person
suffering from hereditary fructose intolerance is not able to metabolize fructose.
Mode of a function of mutagenesis agent

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A gene is a distinct stretch of a DNA that shows something about who someone is.
Genetics is the study of genes and genetic variations and inheritance. Genes vary from one
individual to another and are often inherited. According to Guichard et al5 genes are made of
DNA which is made of a chain of nucleotides. There are four types of nucleotides namely
adenine, cytosine, guanine and thymine. Genetic information is found in the nucleotides.
Guichard et al5 also explained that genes are part of the DNA sequence and there are two types of
DNA sequence namely introns and exons. DNA often replicates itself, therefore, changing the
structure of the gene.
Mutation is the change in the DNA sequence during replication according to Maruyama
et al6. This causes the change in genes and chromosomes. The change in mutation could be
harmful beneficial or even silent in some cases as explained by Maruyama et al6. There are
different types of mutations and vary according to the region in which the sequence of the
genetic material has been changed as explained by Pane et al7. Mutations are classified according
to the cause of mutation, the kind of change caused to the gene or its effect on the function of the
gene.
The first type of mutation is called substitution mutations. In this mutation, a single
nucleotide mapped onto another. The corresponding base pair is altered for organisms with
double-stranded DNA or RNA. It can have different effects depending on the position of the
change. Insertions and deletion is another type of mutation and this involves the removal and
addition of stretches in the nucleotide sequence. According to Pane et al7 they cause frame sheet
mutations and therefore, altering the sequence downstream of amino acids of the mutation site.
They also lead to change in polypeptide length, therefore, creating proteins causing aggregates
that are non-functional. Large-scale mutation is a third type of mutation. This is where changes

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in the nucleotide sequence occur on a large scale. This involves many base pairs and nucleotides.
Amplification is one type of this mutation where segments of genetic materials are present in
multiple copies and another I deletions where a large chunk of genetic material is removed.
According to Kostoff & Lau8 there are different types of mutagenesis agents which
include electromagnetic radiation. Ultra-Violet light causes the formation of pyrimidine dimers
called TT and CC, therefore, causing point mutations. If two dimer occur in one strand of the
DNA this causes, the UV light causes the fusion leading to the formation of thymine dimer. UV
light is absorbed by nitrogenous bases and is maximum at 260nm. The duplication error rate at
the site of thymine dimer because the confirmation of the DNA is changed. For dimers to form
the DNA sequence must have an adjacent pyrimidine in order. Kostoff & Lau8 also ascertained
that a change in a DNA sequence of a gene for example, in addition of a gene, could cause an
exaggeration of a certain characteristic in an organism. Cancer is also another consequence of
ultra-violet light. It can eventually cause death.

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References
1. Bouteldja N, Timson DJ. The biochemical basis of hereditary fructose intolerance.
Journal of inherited metabolic disease. 2010 Apr 1;33(2):105-12.
2. . Goudsmit EM. Carbohydrates and carbohydrate metabolism in Mollusca. Chemical
zoology. 2014 Apr 11;7:219-43.
3. . Lanaspa MA, Sanchez-Lozada LG, Cicerchi C, Li N, Roncal-Jimenez CA, Ishimoto T,
Le M, Garcia GE, Thomas JB, Rivard CJ, Andres-Hernando A. Uric acid stimulates
fructokinase and accelerates fructose metabolism in the development of fatty liver. PloS
one. 2012 Oct 24;7(10):e47948.
4. Coffee EM, Yerkes L, Ewen EP, Zee T, Tolan DR. Increased prevalence of mutant null
alleles that cause hereditary fructose intolerance in the American population. Journal of
inherited metabolic disease. 2010 Feb 1;33(1):33-42.
5. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J,
Bioulac-Sage P, Letexier M, Degos F, Clément B. Integrated analysis of somatic
mutations and focal copy-number changes identifies key genes and pathways in
hepatocellular carcinoma. Nature genetics. 2012 Jun;44(6):694.
6. . Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada
M, Nodera H, Suzuki H, Komure O. Mutations of optineurin in amyotrophic lateral
sclerosis. Nature. 2010 May;465(7295):223.
7. . Pane M, Mazzone ES, Sormani MP, Messina S, Vita GL, Fanelli L, Berardinelli A,
Torrente Y, D'Amico A, Lanzillotta V, Viggiano E. 6 Minute walk test in Duchenne MD
patients with different mutations: 12 month changes. PloS one. 2014 Jan 8;9(1):e83400.

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8. Kostoff RN, Lau CG. Combined biological and health effects of electromagnetic fields
and other agents in the published literature. Technological Forecasting and Social
Change. 2013 Sep 1;80(7):1331-49.