Amino Acid Metabolism Flashcards
Source of METHYL groups in metabolism
PRECURSOR of CYSTEINE
METHIONINE
Synthesized from methionine and ATP
S- ADENOSYLMETHIONINE (SAM)
Enzymes involved in metabolism of sulfur containing amino acid
Methiobine adenosyl transferase Methyl transferase Adenosyyl homocysteinase Methionine synthase Cystathionine B synthase Cystathionase
After donating its methyl group SAM is converted to
S-ADENOSYLHOMOCYSTEINE
Catecholamines are inactivated (catabolized) by
MONOAMINE OXIDASE (MAO) and CATECHOL O METHYLTRANSFERASE (COMT)
NE and Epi are degraded to
VANILLYMANDELIC ACID (VMA)
increased in pheochromocytoma
Dopamine is degraded to
HOMOVANILLIC ACID (HVA)
DOPA Decarboxylase
L-DOPA – DOPAMINE
COFACTOR - B6 (pyridoxine)
Dopamine beta hydroxylase
DOPAMINE – NOREPINEPHRINE
COFACTOR: VITAMIN C
The MC metabolic disorder concerned w/ amino acid
Classic Phenylketonuria
Biochemical defect in PKU
PHENYLALANINE HYDROXYLASE DEFICIENCY
Phenylalanine hydroxylase
L PHENYLALANINE –> L TYROSINE
Phenylalanine hydroxylase
L PHENYLALANINE –> L TYROSINE
Phenylketonuria
ACCUMULATION OF PHENYLKETONES
phenylpyruvate (characteristic odor to the urine)
phenyllactate
phenylacetate
mental retardation musty odor vomiting hyperactive with autistic behavior lighter in their complexion than unaffected siblings
The main organ affected by hyperphenylalaninemia
BRAIN
Treatment of Classical PKU
Dietary control to DECREASE PHENYLALANINE AND INCREASE TYROSINE
AVOID:
HIGH protein foods - meat, dairy, nuts, legumes
starches - bread, potatoes, corn and beans
ALLOWED
LOW protein foods - fruits, nonstarchy vegetables
Congenital deficiency of HEMOGENTISATE OXIDASE in the degradative pathway of tyrosine –> build up of HOMOGENTISIC ACID
ALKAPTONURIA
Alkaptonuria
alkapton bodies –> urine turn black on standing
dark CT (OCHRONOSIS)
benign disease but may have DEBILITATING ARTHRALGIAS
pigment deposition
GARRODS TETRAD
Alkaptonuria
Albinism
Pentosuria
Cystinuria
Treatment for alkaptonuria
aimed at reducing pigment deposition
reduce phenylalanine and tyrosine
VITAMIN C
Defective melanin synthesis from TYROSINE
ALBINISM
absence of copper requiring enzyme TYROSINASE
defective tyrosine transporters
Specialized products from TYROSINE
MELANIN
CATECHOLAMINES
THYROXINE
Type I Tyrosinemias
FUMARYL ACETOACETATE HYDROLASE DEFICIENCY
cabbage like odor
Type II Tyrosinemia
TYROSINE TRANSAMINASE DEFICIENCY
MC inborn error of methionine metabolism
Classic Homocystinuria
Enzyme deficient in Homocystinuria
CYSTATHIONINE B SYNTHASE
COENZYME: Pyridoxal phosphate
Defect in methionine degradation leads to
HIGH PLASMA AND URINARY LEVELS OF HOMOCYSTEINE AND METHIONINE
LOW LEVELS OF CYSTEINE
Homocystinuria
normal at birth
3 y/o - subluxation of the ocular lens (ECTOPIA LENTIS) – severe myopua and iridodonesis (quivering of the iris)
displacement is DOWNWARD
progressive INTELLECTUAL DISABILITY
SKELETAL ABNORMALITIES - tall, thin, w/ elongated limbs, arachnodactyl, pectus excavatum or carinatum, genu valgum, pes cavus
THROMBOEMBOLIC EPISODES - both large and small vessels
- MI
- stroke in the young
Diagnostics of Homocystinuria
ELEVATIONS - methionine and homocystine (or homocysteine)
LOW - cystine in the plasma
Treatment of Homocystinuria
Restriction of Methionine
- limit eggs, fish and meat
- encourage protein from plant foods (soya, nuts)
Supplementation with vitamins B6, B12 and folate
Inherited defect of renal tubular amino acid transporter for (COLA) CYSTINE ORNITHINE LYSINE ARGININE
CYSTINURIA
excess cystine in urine –> precipitation if cystine kidney stones and staghorn calculi
Treatment for Cystinuria
ACETAZOLAMIDE - alkalinize the urine
Defect in the conversion of methylmalonyl CoA to succinyl CoA
Involves metabolism of AA that ate converted to propionyl CoA:
ISOLEUCINE, VALINE, THREONINE and METHIONINE
METHYLMALONIC ACIDEMIA
seizure, encephalopathy, stroke at the age of 1 month to 1 year
Treatment for Methylmalonic Acidemia
Protein Restricted diet (0.5 - 1.5 g/kg/d with L carnitine and cobalamin supplementation
Blocked degradation of branched amino acids (ISOLEUCINE, VALINE, LEUCINE!!) d.t. deficiency in alpha ketoacid dehydrogenase complex
MAPLE SYRUP URINE DISEASE
vomiting, seizures, mental retardation
Treatment for Maple Syrup Urine Disease
Dietary restriction
Limit intake of valine, isoleucine and leucine
Affected infants who are normal at birth develop poor feeding and vomiting in the 1st week of life
lethargy, coma, convulsions
metabolic acidosis
hypertonicity, muscular rigidity with severe opisthonos
Maple Syrup Urine Disease
Function of Histamine and Receptor Responsible for its Action
H1 - smooth muscle contraction; increased vascular permeability
H2 - gastric HCL secretion
H3 - synthesis and release of histamine in the brain
Metabolic error d.t. deficiency of HISTIDASE
histidase - converts HISTIDINE to UROCONATE
HISTIDINEMIA
autosomal recessive
benign
