Download Phenylketonuria

Metabolic Pathways
Metabolism is the sum total of all the chemical reactions going on in the body: digestion of
carbohydrates, building proteins into “gates” in lipid cell membranes, breaking down alcohol in
the liver, making sweat and so on. Many of these are chain reactions, where the product of one
becomes the reactant of the next – these are called metabolic pathways. Remember, each
reaction in a metabolic pathway wiil be controlled by an enzyme and every enzyme is coded for
by a gene. The metabolism of phenylalanine is a well-studied metabolic pathway.
When we ingest protein it is digested down to its component amino acids and these are
transported around the body in the blood. The liver reactions convert many of these into useful
substances but what is not used is broken down and eventually passes out in the urine.
One such amino acid is phenylalanine. This is an essential amino acid for us - we can’t make
it in our body, we need to have it in our diet. The diagram below shows a simplified version of
the pathway for its metabolism.
In
the
liver
enzymes convert
phenylalanine into
a
number
of
substances
the
body needs. What
can’t be used is
converted
to
carbon dioxide and
water in the end.
But mutations in
the genes making
enzymes early in
the pathway can
lead
to
some
notable metabolic
disorders.
In the 1st step of
the pathway the
enzyme
PAH
converts phenylalanine
into
tyrosine. If this
enzyme is faulty it
will instead make
phenylpyruvic
acid,
which
accumulates,
leading
to
the
metabolic disorder
phenylketonuria
(or PKU). In this
condition the liver
is
unable
to
remove
phenylpyruvic acid, which
ends up being carried around the body in the blood and excreted in the urine (where it turns
black on exposure to air). Phenylpyruvic acid harms nerve cells so it can result in problems with
brain development, leading to mental retardation and seizures. As well, the lack of tyrosine
means that the metabolic pathway is totally disrupted and other substances needed by the body
are not made.
All babies are tested for PKU soon after birth as the build up of phenylpyruvic acid can be
prevented by a combination of diet and medication. People with PKU must have a special diet
during their childhood and teenage years, avoiding foods that are high in phenylalanine. They
also need to take tyrosine supplements to allow the body to produce melanin and thyroxin.
PKU is a good example of how genes determine how our bodies react to nutrients in our food.
Albinism
An interesting sideline to this is that albinism is also caused by
another mutation in the same metabolic pathway.
Melanin is a protein which colours our skin, eyes, & hair &
protects them from the burning effects of the UV light from the
sun. It is made by melanocytes, which are cells found in the
bottom layer of skin.
Human albinos are born with no melanin in their skin, hair & eyes.
Their hair and skin is white, while their eyes appear red because
the lack of colour in the iris unmasks the red haemoglobin
pigment in blood vessels in the retina. Albinos are susceptible to
sunburn & skin cancers. This is a rare condition, affecting people
from all races with a frequency of about 1 in 20,000. In NZ about
1 in 70 people have a gene for albinism.
Albinism inheritance shows the Mendelian pattern of an autosomal recessive phenotype in
many other animals too. This means both parents need to carry the recessive allele (a mutation
of the dominant) for a child to be albino. In an albino, melanocytes are present in normal
numbers in the skin, hair and iris, but lack melanin pigment.
This mutation results in a defective enzyme in the metabolic
pathway that produces melanin. Individuals with a recessive
aa genotype lack the tyrosinase enzyme needed to convert
tyrosine into melanin. The mutation interferes with the shape
of the tyrosinase enzyme, especially in the site that binds
copper.
Albinism Trust Members at a Waikato Meeting
Some questions to consider:
1. Explain what is meant by the terms, metabolism, metabolic pathway, enzyme, gene,
essential amino acid, mutation
2. Name 3 products of the metabolism of phenylalanine.
3. Copy and complete a table like this
Metabolic Faulty enzyme
Disorder responsible
PKU
Albinism
Chemical causing Is the disorder due to having none of this
the problem
chemical, too little or too much?
4. Why do you think all babies are now tested for PKU?
5. Describe how a doctor might test for PKU – be as specific as you can.
6. Explain why a person with PKU would have a paler skin.
7. Why might albinos be more susceptible to sunburn & skin cancer?
8. If 1 in 70 people have the gene for albinism why is the condition only seen in 1 in 20,000?
9. Describe 3 ways in which albinism may impact on an animal’s life.
10. What is an autosomal recessive condition?
11. Explain how an enzyme might develop faults.
12. What sorts of faults will disrupt enzyme function?
13. Discuss the role of enzymes in metabolic pathways, using this one as an example.
14. Examine the food labels on protein containing foods – sort the ones that would be ok for a
PKU sufferer from those that would not - look for phenylalanine in the ingredients.
15. See if you can find other substances whose metabolism forms a pathway.