AMINOACIDOPATHIES Flashcards
Rare, inherited disorders of amino acid metabolism
AMINOACIDOPATHIES
2 abnormalities in AMINOACIDOPATHIES
Specific enzyme (defect or deficiency) in metabolic pathway or membrane transport system
PHENYLKETONURIA (PKU) is the Total absence of activity of ___
PHENYLALANINE HYDROXYLASE
PHENYLALANINE HYDROXYLASE catalyzes the conversion of
phenylalanine to ___
tyrosine
There is an accumulation of levels of Phenylalanine and its metabolites (eg. phenylpyruvic acid, phenylpyruvate also known as phenylketone, and phenylacetic
PHENYLKETONURIA (PKU)
Increase of Phenylalanine on the blood
Hyperphenylalaninemia
There is a presence of Phenylalanine in the Urine
Phenylketonuria
The presence of Phe in urine happens because it surpases the amount of proteins or metabolites that the kidney can filter or what we call ___
Renal Threshold
Phenylketonuria causes the urine to have a characteristic ___ odor.
“musty” or “mousy”
Complications in infants and children with Phenylketonuria
retarded mental development and microcephaly
Fetal effects of maternal PKU are preventable
if the mother maintains a ___ before conception and throughout pregnancy.
phenylalanine-restricted diet
Metabolites of Phenylalanine
Phenylpyruvate, Phenylacetic acid, Phenylacetylglutamine
is derived from the deamination of phenylalanine
Phenylpyruvate
Decarboxylation and Oxidation of Phenylpyruvate
Phenylacetic acid
Occurs as a result of the toxic effects of the brain of phenylpyruvate or
one of its metabolic by-products
Retarded mental development
Retarded mental development occurs in what week of life
2nd or 3rd week of life
glutamine conjugate of phenylacetate
Phenylacetylglutamine
a semiquantitative, bacterial inhibition assay for phenylalanine based on the ability of phenylalanine to facilitate bacterial growth in a culture medium despite the presence of a growth inhibitor.
Guthrie Bacterial Inhibition Assay
in Guthrie Bacterial Inhibition Assay, spores of __ are incorporated into an agar plate that contains ___ (antagonist or inhibitor)
Bacillus subtilis; beta-2- thienylalanine
If blood phenylalanine exceeds
___ mg/dL, phenylalanine
counteracts the antagonist
and bacterial growth occurs
3-4
In Guthrie Bacterial Inhibition
Assay:
Presence of Bacterial Halo = __
Absence of Bacterial Halo = __
Positive
Negative
direct measurement of
phenylalanine in dried blood
filter disks
Microfluorometric assay
Microfluorometric assay in phenylketonuria is based on the ___ of a
complex formed of
___ in
the presence of a dipeptide ___
fluorescence; phenylalanine-ninhydrin-copper; Lleucyl-L-alanine
in Microfluorometric assay in phenylketonuria:
Excitation wavelengths = ___
emission wavelengths = ___
360 nm
530 nm
Microfluorometric assay in Phenylketonuria requires pretreatment of the dried blood filter disk with ___
trichloroacetic acid (TCA)
The reference method or standard method for detecting PKU
High-Performance Liquid Chromatography (HPLC)
In High-Performance Liquid Chromatography (HPLC), phenylketonuria is detected in newborn’s blood in ___ mg/dL
1.2 -3.4 mg/dl (70/200 umol/L)
in Microfluorometric Assay, the microtiter plate is made of a mixture of ___, ____, ___ in the presence of ___.
ninhydrin, succinate, and leucylalanine; copper tartrate
Used for Monitoring in phenylketonuria and a Reagent Strip Test
Urine Test
Urine Test involves the reaction of ___ with __ in urine to produce a ___ color
ferric chloride; phenylpyruvic acid; green
Characterized by excretion of tyrosine and tyrosine catabolites in urine
TYROSINEMIA
is the most severe form
of TYROSINEMIA
Type I Tyrosinemia
a type of Tyrosinemia which symptoms are failure to thrive, diarrhea, vomiting, jaundice, a cabbage-like odor, distended abdomen, swelling of the legs, and an increased predisposition for bleeding.
Type I Tyrosinemia
complications of tyrosinemia
Leads to liver damage (Cirrhosis and liver cancer)
type 3 tyrosinemia enzyme deficiency
4-hydroxy-phenylpyruvic acid oxidase
type 1 tyrosinemia enzyme deficiency
Fumarylacetoacetate (FAA) hydrolase
type 2 tyrosinemia enzyme deficiency
tyrosine aminotransferase
ALKAPTONURIA is the lack of ___
homogentisate oxidase
homogentisic acid (HGA) accumulates in connective tissue
causing generalized pigmentation
of these tissues called ___, an
arthritis-like degeneration
Ochronosis
Accumulation of homogentisic acid (HGA) is characterized by ___ of urine
darkening
2 clinical manifestations of alkaptonuria
ochronosis and darkening of urine
Familial inheritance aminoacidopathy
ALKAPTONURIA
elevated concentrations of homogentisic acid (HGA) in the blood
alkaptonuria
Characterized by burnt sugar odor of the urine, breath, and skin
MAPLE SYRUP URINE DISEASE
MAPLE SYRUP URINE DISEASE lacks the enzyme ___
branched-chain alpha-ketoacid decarboxylase
alpha-ketoacid decarboxylase blocks the normal metabolism of
Leucine, Isoleucine and Valine
COMPLICATIONS:
Lethargy, failure to thrive, Muscle rigidity, Respiratory irregularities,
Mental retardation, Convulsions, Acidosis and hypoglycemia
MAPLE SYRUP URINE DISEASE
in Microfluorometric assay in MAPLE SYRUP URINE DISEASE, pretreatment used are
solvent mixture of methanol and acetone
in Microfluorometric assay in MAPLE SYRUP URINE DISEASE, extract used is
Leucine dehydrogenase
in Microfluorometric Assay in Maple Syrup Disease:
excitation wavelength = ___
emission wavelength = ___
360 nm
450 nm
above __ mg/dL is indicative of MAPLE SYRUP URINE DISEASE
4
ISOVALERIC ACIDEMIA
is the deficiency of ___ in leucine pathway
isovaleryl-CoA dehydrogenase
odor of urine in ISOVALERIC ACIDEMIA
sweaty feet
in HOMOCYSTINURIA, there is an increase in ___
homocysteine
Intermediate amino acid in the synthesis of cysteine from
methionine
Homocysteine
In homocystinuria, there is an impaired activity of ___ which converts homocysteine to
___
cystathionine beta-synthase; cysteine
– Cysteine and homocysteine are reduced by sodium cyanide to
free-thiol
– Then, reacted to sodium nitroprusside to produce a ___color
Cyanide-Nitroprusside Urine Spot Test; red-purple
Confirmation for homocysteine
* Silver nitrate reduces homocysteine to form __ color
Silver-nitroprusside Test; reddish
COMPLICATIONS:
– Thromboembolism, Cardiovascular risk, Atherosclerotic
disease, Low folate concentrations, Vitamin B12 deficiency
HOMOCYSTINURIA
2 diseases that results from inherited enzyme deficiencies in the urea cycle
CITRULLINEMIA and ARGININOSUCCINIC ACIDURIA
TYPE 1 CITRULLINEMIA lacks the enzyme ___
argininosuccinic acid synthetase (ASS)
complications of citrullinemia
Vomiting, high ammonia levels and Mental retardation
caused by a mutation of the gene that would provide instructions for
making the protein citrin
TYPE 2 CITRULLINEMIA
lack of __ inhibits the urea cycle and disrupts the production of proteins and
nucleotides and this happens in what type of disease?
citrin; Type II Citrullinemia
in Type I Citrullinemia, there is an increase in ___ and it will not be converted to ___
citrulline; arginosuccinic acid
The resulting accumulation of ___ and other toxic substances in citrullinemia leads to confusion, restlessness, memory loss, personality changes, seizures, and coma
ammonia
deficiency in argininosuccinate lyase (ASL) prevents the conversion of argininosuccinic acid into ___
arginine
in ARGININOSUCCINIC ACIDURIA, there is deficiency in ___
argininosuccinate lyase (ASL)
a defect in the amino acid transport system rather than a metabolic
enzyme deficiency
CYSTINURIA
ARGININOSUCCINIC ACIDURIA complications
Vomiting, high ammonia levels and Mental retardation
in ARGININOSUCCINIC ACIDURIA, there is accumulation of __
argininosuccinate
in cystinuria, there is Increased urinary excretion of ___
cystine
Increased urinary excretion of cystine resulting from genetic defect in the ___
renal resorptive mechanism
Cystine is insoluble and tends to precipitate in the kidney tubules and cause ___
URINARY CALCULI or kidney stones
