Phenylketonuria (PKU) is an inherited metabolic disorder caused by a recessive gene, meaning a child must inherit a copy of the mutated allele from each parent to develop the condition. Individuals with PKU lack the enzyme needed to metabolize the amino acid phenylalanine. If the condition is not treated through a regulated diet, the resulting buildup of phenylalanine in the brain becomes toxic, leading to severe consequences such as significant deficits in cognitive function, intellectual disability, seizures, and an increased risk of various psychiatric disorders.

Phenylketonuria (PKU)

- Absence of enzyme homogentisate oxigenase
- Excreted in urine and produces melanin-like dark pigment when oxidized by air - black urine
- Relatively benign disease as homogentisate can be excreted


Alkaptonuria

- Branched-chain alpha-keto acid dehydrogenase complex is missing or defective
- Oxidative decarboxylation of alpha-ketoacids from branched-chain AA, (Ile Val Leu) does not occur
- Build up of these alpha-ketoacids and branched-chain AA in blood and urine
- Severe mental deficiency
- Failure to thrive
- Screening in NB blood sample
- Restricted diet


Maple-Syrup urine disease

- Phenylketonuria (PKU)
- Alkaptonuria
- Maple-Syrup urine disease

Michigan State University

Amino acids make up every protein. There are 20 total amino acids each with a unique side-chain group. Some additional amino acids are listed, but only 20 are coded from DNA directly. These side-chains allow for chemical interactions like sulfide bonds, hydrogen bonds, and ionic bonds. Amino acids are further divided by being non-polar, polar, and charged. They link together with a peptide bond making a string of amino acids a polypeptide. Finally, each amino acids is assigned a name, a three-letter symbol and a one-letter symbol. 


Amino Acids are involved in many systems and issues with its breakdown can cause diseases: 
- In the liver: major site of urea production in the urea cycle
- Alpha-keto acids can deliver amino groups to the liver 
- Ammonium is toxic: lethargy, headache, vomiting, seizures, death
- Seen in compromised liver


Amino Acids

- Enzyme: Glutamate dehydrogenase
- 1. Oxidation (NAD+ or NADP+) of glutamate to yield Schiff-base intermediate
- 2. Hydrolysis deamination of intermediate to make alpha-ketoglutarate
- Glutamate -> alpha-ketoglutarate and ammonium
- Mitochondrial enzyme: NH4+ is toxic
> Reactions close to equilibrium

> Usually pulled forward by loss of NH4+


Oxidative deamination of amino acids to yield glutamate in liver

- 1st amino group from ammonium, second amino group from aspartate, carbon comes from bicarbonate
- ** Fumarate is formed from the breakdown of argininosuccinate in the urea cycle, and links the urea cycle with the TCA cycle
- First reactions occur in the mitochondrial matrix

OVERVIEW
- Carbamoyl Phosphate synthesis
- Formation of Citrulline (in mitochondrial matrix)
- Formation of Argininosuccinate (cytoplasm)
- Formation of Fumarate
- Cleavage

- Eventually converted to OAA, cycle can start again


Urea Cycle

Inborn Errors of Amino Acid Catabolism

Protein structure is the 3-dimensional assembly caused by the string of amino acids translated from RNA . Protein structures varies immensely due to the assembly of the amino acids.
There are four subdivisions of proteins structures:
- Primary structure
- Secondary structure
- Tertiary structure 
- Quaternary structure 

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