Amino Acids Objectives

general structure of amino acid

• amino group

• r-group

• carboxyl group

3 sources of amino acid pool

• dietary protein

• tissue breakdown

• synthesis of non-essential amino acids

Gluconeogensis

• formation of glucose from non-carbohydrate sources

• Starting: glycerol, fatty acids, and AA

• Ending: glucose

• occurs in liver

Transamination

• transfer of amino group to make different amino acid

• Starting: any amino acid

• ending: alpha-keto acid

• occurs in liver

Deamination

• removal of amino group forming toxic ammonia

• Starting: amino acid

• Ending: ammonia

• occurs in liver

Renal aminoaciduria

• defective renal reabsorption

• Amino lvls in:

  • plasma = decrease or normal

  • urine = increase

Overflow aminoaciduria

• plasma lvl exceeds renal threshold for reabsorption

• amino acid lvls in:

  • plasma = increase

  • urine = increase

Cystinuria (renal aminoaciduria)

• error of AA transport (renal tubular reabsorption defect)

• COAL: increases Cystine, Ornithine, Lysine, and Arginine in urine

• Symptoms: ??

Hartnup Disease (renal aminoaciduria)

• renal tubular reabsorption defect for neutral AA

• neutral monocarboxylic AA increase in urine (ex: tryptophan)

• Symptoms: ??

Fanconi Syndrome (renal aminoaciduria)

• renal disfunction of proximal convoluted tubule (RIP the “PCT”)

• impaired reabsorption of AA, Calcium, bicarbonate, phosphate, urate and glucose

• Symptoms: ??

Phenylketonuria (overflow aminoaciduria)

• deficiency/absence of phenylalanine hydroxylase enzyme

• Increase serum phenylalanine, decrease serum tyrosine

• musty/mousy odor body/urine, spastic movements/seizures, eczema etc

Tyrosinemia Type 1 (overflow aminoaciduria)

• fumarylacetoacetase deficiency

• increase serum and urine tyrosine lvls, increase serum methionine

• most severe

• kidney and liver issues

Tyrosinemia Type 2 (overflow aminoaciduria)

• tyrosine aminotransferase deficiency

• increase serum and urine tyrosine

• serum methionine NOT elevated

• skin and eye issues

Tyrosinemia Type 3 (overflow aminoaciduria)

• 4-hydroxyphenyl-pyruvate dioxygenase deficiency

• increase PHPPA lvls

• very rare

Alkaptonuria (overflow aminoaciduria)

• homogentisic acid oxidase deficiency

• increase homo. acid in serum and urine

Homocystinuria (overflow aminoaciduria)

• CBS deficiency (cystathionine beta synthase)

• methionine and homocysteine increase in serum and urine

• skeleton abnormalities

Maple Syrup urine Disease (MSUD) (overflow aminoaciduria)

• alpha-ketoacid decarboxylase defect

• branched chain amino acids

• ketone bodies increase, ketoacids in blood and urine

Specific physical characteristics of urine from Alkaptonuria and Maple Syrup urine Disease

Alkaptonuria:

• urine turns black when exposed to air

Maple Syrup:

• has a sweet smelling urine

Citrullinemia Type 1 (urea cycle disorder)

• deficiency of arginosuccinate synthetase (ASS)

• ammonia lvl increase in plasma

Citrullinemia Type 2 (urea cycle disorder)

• deficiency of mitochondrial aspartate transporter (MAT)

• ammonia lvl increase

Arginiosuccinic aciduria (urea cycle disorder)

• deficiency of arginosuccinate lyase

• ammonia lvls increase

General Principles of TLC

• solid stationary phase and liquid mobile phase

• solute separates based on polarity for phases

General Principles of Gas-liquid chromatography

• takes up liquid sample, turns to gas, ions separated by absorption on fixed charges

• mobile phase has competing ions

General Principles of GC Mass Spec.

• converted to gaseous ions separated by mass filters based on mass-charge ratios

3 quantitative tests for presence of aminoacidurias

• DNA abnormality

• Enzyme defect

• metabolic abnormalities that result from defect