Amino Acids: Structure, Classes, and More

• Amino acids are the fundamental building blocks of proteins and crucial biological compounds.
• Each amino acid contains an amine (-NH2) group, a carboxylic acid (-COOH) group, and a unique side chain denoted as (R).
• The structure, properties and diversity due to these side chains are responsible for the 20 amino acids.

Classification of Amino Acids

• Nonessential amino acids are synthesised by the body.
• Essential amino acids can't be synthesized by the body, they must be obtained from the diet.
• Conditionally essential amino acids cannot be synthesised in the human body due to illness or lack of necessary precursors.
• Examples of conditionally essential amino acids inclue cysteine (important for premature infants) and tyrosine (relevant in PKU).

Essential Amino Acids

• Essential amino acids can't be synthesised by the body, they must be obtained from the diet.
• Essential Amino Acids: Phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine.

Non-Essential Amino Acids

• The 10 amino acids that can be produced by the body include: alanine, asparagine, glutamate, glutamine, cysteine, aspartate, glycine, tyrosine, proline and serine.
• A mnemonic for recalling these amino acids: Almost All Girls Go Crazy After Going To Panorama Stores.

pH and Chemical Properties

• At low pH (high proton concentration), both amine and carboxylic acid groups are protonated (-NH3+ & -COOH).
• At high pH (low proton concentration), both amine and carboxylic acid groups are deprotonated (-NH2 & -COO−).
• At neutral pH, amines are protonated (-NH3+), and carboxylates are deprotonated (-COO−).

Metabolic Disorders Relation

• Amino acids serve as the building blocks of proteins and fulfill numerous bodily functions.
• Hereditary disorders disrupting amino acid metabolism arise from defects in either amino acid breakdown or their cellular transport.
• Due to the early onset of symptoms, newborns are routinely screened for these disorders.

Aminoacidopathies

• Aminoacidopathies are rare, inherited "inborn errors" of amino acid metabolism.
• Screening for these diseases varies by country, depending on the specific diseases suspected.

Phenylketonuria (PKU)

• Accumulation of phenylalanine in blood, CSF and urine causing mental retardation beginning in the first week of life.
• Phenylketonuria (PKU) is inherited as an autosomal recessive trait.
• PKU occurs in about 1 in 15,000 births.
• The classic form of PKU causes absence of activity of the enzyme phenylalanine hydroxylase (PAH).
• PAHcatalyzes the conversion of phenylalanine to tyrosine.

Normal Phenylalanine Metabolism

• Dietary sources, particularly plant proteins phenylalanine which is broken down (via enzyme PAH) into Tyrosine which is used in body proteins.

Abnormal Phenylalanine Metabolism

• Dietary sources, particularly plant proteins phenylalanine increases, resulting in phenylacetic acid and hydroxyphenylacetic acid
• Deficiency of the enzyme PAH is the cause of the elevated PHenylalanine levels.

Phenylketonuria Symptoms

• When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (Phenylketone) which can be detected in urine.
• Phenylketone can cause significant brain problems.
• Phenylalanine derivative compounds are found in both the blood and the urine of a PKU patient

Determining Phenylketonuria

• Normal phenylalanine levels are up to 120 µmole/l.
• Results are usually greater than 1200 µmole/l in the absence of the enzyme PAH.
• Untreated, PA will be as high as 2.4 mM/L.

Preventatives for Phenylketonuria PKU

• Brain damage can be avoided if the disease is detected at birth and the infant is maintained on a diet containing very low levels of phenylalanine.
• Women with PKU who are untreated during pregnancy typically give birth to babies who are microcephalic and mentally retarded.
• The fetal effects of maternal PKU are preventable.

Phenylketonuria Etilogy

• Autosomal recessive disorder is from a mutation in PAH gene.
• Located on the 12th chromosome.
• A carrier does not have symptoms of disorder.

Symptoms of Phenylketonuria

• Most babies with phenylketonuria appear healthy at birth.
• Symptoms usually only develop due to complications that arise if the condition is not treated properly.
• Untreated effects on the brain and nervous system include: learning disabilities, behavioural difficulties and/or epilepsy.

Other Symptoms of Phenylketonuria

• Those with disorder often have lighter skin, hair, and eyes than siblings.
• Other symptoms include: eczema, recurrent vomiting, jerking movements in arms and legs, tremors, mood disorders, or microcephaly.

Other Causes of High Phenylalanine

• Defect in the enzymes needed for the regeneration and synthesis of Tetrahydrobiopterin (BH4).
• BH4 is a cofactor required for the enzymatic hydroxylation of the aromatic amino acids phenylalanine, tyrosine, and tryptophan.
• A deficiency of BH4 results in elevated blood levels

Tests for Phenylketonuria (PKU)

• The upper limit of normal for a phenylalanine level is 120 mol/L .
• "The Guthrie test" is semiquantitative, bacterial inhibition assay for phenylalanine, it uses the ability of phenylalanine .
• In newborns, blood is collected on a filter paper and punched out into an agar containing Bacillus subtilis and B-2-thienylalanine,
• B-2-thienylalanine supports growth.
• In the presence of phenylalanine, it can be overcome and the bacteria can grow

Guthrie Assay

• The Guthrie assay is sensitive enough to detect serum phenylalanine levels of 180-240 umol/L.
• A bacterial halo on newborn blood tests indicates PKU.
• The healthy control is no bacterial growth however positive controls with increasing serum levels show halos
• Absence of bacterial growth in the blood test indicates healthy infant.

Phenylketonuria Diagnosis

• Screening on blood samples is during the first week of life.
• If PKU is confirmed, the child will need regular blood tests.
• A PKU test is done one or two days after baby.
• Done once the baby is 24 hours old, consuming some proteins allowing accurate results.
• Few drops of blood are from baby's heel or the bend the baby's arm.
• Positive results should be quanitatively measured.

Phenylketonuria Treatment

• This disorder can be successively treated with a low-protein diet and dietary supplements.
• Strict adherance is crucial.
• It is recommended those diagnosed continue said diet into adulthood in order improve mental and phsical health

Hereditary Details

• Two people who conceive a child must both be the carriers of the defective gene in order for their child to to express disorder.
• The "carrier" for PKU shows no symptoms.
• A PAH (Phenylalanine Hydroxylase gene) tolerance is 20 mg/kg/day.
• Missense mutations and deletions occur in single mutant recessive allele.
• Excess plant protein in diet also causes a disorder.

Treatment Details

• Those with PKU require ongoing doctor visits, dietary restrictions, and monitoring blood's phenylalanine levels.