DISORDERS OF AMINO ACIDS

1. DISORDERS OFAMINO ACIDS
A SEMINAR PREPARED
BY
LAWAL, BELLO DANCHADI
ADM NO: 22210705001
DEPARTMENT OF CHEMICAL PATHOLOGY AND IMMUNOLOGY
USMANU DANFODIYO UNIVERSITY, SOKOTO.
MARCH, 2023

2. Introduction
What is Amino Acid?
 Amino acids are the building blocks of protein. Amino acid are organic compound which
contain amine (-NH2) and carboxyl (-COOH) as a functional groups along with the side
chainn (R) group which is specific for each amino acid, R-CH(NH2)COOH.
 Structure of amino acid

3. Introduction cont'd
 There are 20 amino acids which are grouped as
1. 9 essential amino acids: cannot be synthesized by the body, they must be
included in diet (histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, threonine, tryptophan, and valine).
2. 11 Non-essential: are synthesized by the body: Alanine, Arginine,
Asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine,
Proline, Serine, and tyrosine.
Amino Acid Disorders
 Something goes wrong with metabolic process is called disorder. But when
something goes wrong with metabolism of amino acid specifically at that
time it is termed as disorders associated with amino acid metabolism.

4. There are many disorders associated with amino acid metabolism such as:
• Phenylketonuria
• Marple syrup urine disease (MSUD)
• Albinism
• Homocystinuria
• Alkaptonuria
• Primary hyperoxaluria
• Cystinuria
• Tyroxinaemia
• Histidinaemia
• Hartnup disease

5. Phenylketonuria (PKU)
 Most common disease of amino acid metabolism
 Occur due to deficiency of phenylalanine hydroxylase enzyme
 Unable to break down phenylalanine.
 This causes a buildup of phenylalanine in the body
 Results in hyperphenylalaninemia and tyrosine deficiency

6. Phenylketonuria (PKU) Cont.
Other Reason for hyperphenylalaninemia:
 Deficiency in Tetrahydrobiopterin (BH4)
 Conversion of Phenylalanine to Tyrosine requires BH4, so even though
phenylalanine hydroxylase level is normal, the enzyme will not function
without it.
 Hence Phenylalanine accumulates.
This Deficiency of BH4 Caused by deficiency of:
1- Dihydropteridine reductase.
2- Dihydrobiopterine synthetase .
3- Carbinolamine dehydratase.
Leading to a typical PKU

7. Characteristics of PKU
Note:
• (normally tyrosine is not an essential amino acid but in the case of PKU it becomes
essential. Therefore tyrosine supplements are given to the patient)
“Atypical hyperphenylalaninemia”
 Deficiency in dihydropteridine reductase, dihydrobiopterine synthetase enzyme es and
Carbinolamine dehydratase. (which recycles BH4 when deficient BH4 can not
be recycled back deficiency in BH4 No Tyrosine formation in the body)
 In the absence of BH4, Phenylalanine will not be converted to Tyrosine
 Tyrosine will not be converted to catecholamine and tryptophan will not be converted
to serotonin as they require BH4
 Catecholamine and serotonin are neurotransmitters
 Elevated phenylalanine in tissues, plasma, urine
 Phenylalanine is degraded to phenyllactate, phenylacetate, phenylpyruvate
 Gives urine a mousy odor

9. Symptoms of PKU
• CNS symptoms: Mental retardation, failure to walk or talk, seizures, microcephaly,
Tremors etc.
• Hypopigmentation – fair hair, light skin color and blue eyes
• Urine has a musty (mousy) odor.
Diagnosis:
• Prenatal diagnosis is done by detecting gene mutation in fetus.
• Neonatal diagnosis in infants is done by measuring levels of blood Phenylalanine. (24-48
hours after birth, phenylalanine levels are measured to check for any deficiencies)
Treatment:
• Life long Phenylalanine-restricted diet and Tyrosine supplementation.
• Medication- Sapropterin (Kuvan) for the treatment of PKU.
• Sapropterin helps lower phenylalanine levels.

10. Maple syrup Urine disease (MSUD)
• Due to deficiency of branched chain α-keto acid dehydrogenase (BCKD).
• This enzyme decarboxylates leucine, isoleucine and valine. When BCKD is deficient,
these amino acids and their keto-acids accumulate in blood.
Sign and Symptoms of MSUD
mental retardation, physical disability, metabolic acidosis, lethargy, seizures, high-pitched
cry, weight loss, poor appetites, irregular sleep pattern, poor growth, weak sucking ability,
maple sugar odor of urine (sweet smell),
Types of MSUD
1. Classic type:
• Most common and severe form of the condition. due to little or no activity of branched
chain α-keto acid dehydrogenase – about 2% or less of the normal activity.
• Symptoms are present in newborns within few days of birth.
• Onset is usually triggered when the infant’s body begin to process protein from feedings.

11. Types of MSUD cont’d
2. Intermediate:
• Is a rare version of MSUD,
• Peoples with this type of MSUD have a higher level of enzyme activity than classic MSUD –
about 3 – 8% of the normal activity.
3. Intermittent forms:
• This form does not interfere with physical and intellectual growth and development.
• Symptoms usually don’t appear until a child is between 1 – 2 years of age.
• It’s a milder form of classic MSUD. Individual have a significant enzyme activity – about 8- 15%
of the normal activity
• The initial reaction of the disease occurs when the child experiences stress, illness or an unusual
increase in protein.
4. Thiamine-responsive form:
• This is rare form of the condition, often improves with large dose of thiamine, or vitamin B1.
• Symptoms usually occur after infancy, even though thiamine can be beneficial, dietary restrictions
also necessary.

12. Degradation of branched-chain amino acids: valine, isoleucine and leucine.
Deficiency of branched chain α-keto acid dehydrogenase leads to MSUD.

13. Treatment for Maple syrup urine disease
• Treatment involved dietary restriction of the amino acids leucine,
isoleucine, and valine.
• Patients can be treated with an intravenous (given through a vein) solution
that helps the body use up excess leucine, isoleucine, and valine for
protein synthesis.
• Gene therapy is also a potential future treatment for patients with MSUD.
This treatment would involve replacing the mutated gene with a good
copy, allowing the patient's cells to make a functional BCKD protein
complex and break down the excess amino acids.

14. Albinism
First: What is albinism?
• It is a disease of Tyrosine metabolism, It is occur due to absence or defect in tyrosinase
enzyme. This enzyme is involved in melanin production.
• This condition is totally opposite of melanism. An organism with complete absence of melanin
is called an albino.
• Genetic disorder in which humans have complete or partial absence of pigment in skin, hair
and eyes. Due to lack of skin pigment, the person get more susceptible to sunburn and skin
cancer.
• It is rear diseases
Second: What is Melanin?
• Melanin is a pigment of hair, skin and eyes.
Third: Why does it happen?
• It happens due to Tyrosinase deficiency, which causes Melanin deficiency.
• Melanin is absent in Albino patients, so the hair, and skin appear white. Eyes are red along with
vision defects and photophobia.

15. Causes of Albinism
• It is caused by the deficiency of melanocyte tyrosinase, an enzyme involved in melanin
production.
• There are two forms of albinism
• Hypomelanism or hypomelanosis
• Amelanosis
• Symptoms and effects: lack of pigmentation, white hair, pink skin, red eyes.
• Treatment:
• Albinism is a genetic disorder, and there is currently no cure.
• Treatment focuses on getting proper eye care and monitoring skin for the problems.

16. Albinism

17. Homocystinuria
• Due to deficiency of cystathionine β-synthase which leads to defects in homocysteine
metabolism.
• Converts homocysteine to cystathionine. (cysteine is a non-essential amino acid.
• The enzyme cystathionine beta-synthase is required for the early synthesis of cysteine;
when deficient cysteine becomes essential amino-acid).
• High plasma and urine levels of homocysteine and methionine and low levels of
cysteine.
• High levels of homocysteine is a risk factor for atherosclerosis and heart diseases.
Symptoms
• Skeletal abnormalities, osteoporosis, mental retardation, displacement of eye lens,
nearsightedness, etc...

18. Homocysteinuria

19. Treatment of homocysteinuria
• Oral administration of vitamins B6
• Vitamin B6 is a cofactor of cystathionine β-synthase
• Methionine-restricted diet.
Hyperhomocysteinemia is also associated with:
• Neural tube defect (spina bifida)
• Vascular disease (atherosclerosis)
• A risk factor of heart disease

20. Alkaptonuria
• Rare disease of phenylalanine and tyrosine degradation.
• Due to deficiency of homogentisic acid oxidase. Lead to accumulation of
homogentisic acid (molecule produced in the tyrosine degradation pathway) in
the tissue and cartilage) leads to alkaptonuria.
• Homogentisic aciduria: elevated homogentisic acid in urine

21. Characteristics of Alkaptonuria
• Homogentisic aciduria: elevated homogentisic
acid in urine which is oxidized to dark pigment
over time (only symptoms during childhood)
• Arthritis, Black pigmentation of cartilage, tissue
• Usually asymptomatic until adulthood
Treatment:
• Restricted intake of tyrosine and phenylalanine
reduces homogentisic acid and dark pigmentation

22. Summary
Diseases Enzymes Amino acids involved
Phenylketonuria Phenylalanine hydroxylase Phenylalanine
Maple syrup urine disease Alpha-ketoacid dehydrogenase Isoleucine, leucine
and valine
Albinism Tyrosinase Tyrosine
Homocystinuria Cystathionine β-synthase Methionine
Alkaptonuria Homogentisic acid oxidase Tyrosine and phenylalanine

23. Thank You!