PROTEINS Flashcards
enzyme deficient in PKU
phenylalanine hydroxylase
without PAH enzyme, what is the value of phenylalanine levels?
> 1,200 umol/L
newborn upper limit for pku
120umol/L or 2mg/dL
value of phenylalanine in untreated classic PKU
as high as 2.4 mM/L
what are the metabolites of phenylalanine that may be present in urine sample of a px with PKU?
- phenylpyruvate or phenylketone
- phenylpyruvicacid
-phenyllactic acid
odor of urine in PKU?
musty odor
phenylalanine levels of partial deficiencies of PAH or “mild pku”
600-1200 umol/L
Non-PKU mild hyperphenylalaninemia
180-600 umol/L
is a co – factor in the
enzymatic hydroxylation of phenylalanine, tryptophan and tyrosine
tetrahydrobiopterin
a non-protein chemical/entity that
must bind to a particular enzyme before
reaction occurs
co-factor
goal of pku treatment
maintain blood level of phenylalanine (2-10 mg/dL or 120- 160 μmol/L)
first drug to manage pku?
kuvan (sapropterin dihydrochloride)
action of kuvan?
helps reduce the phenylalanine levels by increasing the activity of PAH enzyme
color of urine in ferric chloride tube test for PKU
permanent blue green color
sensitivity of Guthrie Inhibition Test for PKU
180-240 umol/L
inhibitor of B. subtilis in PKU
B2-thienlyalanine
Describes the ability of phenylalanine to facilitate bacterial growth in a culture medium even under the presence of inhibitor
Guthrie Test or Guthrie Inhibition Assay
- Direct measurement of phenylalanine in dried blood filter disks; quantitative
- Principle: It is based on the fluorescence of a complex formed of phenylalanine– ninhydrin–copper in the presence of a dipeptide.
microfluorometric assay
wavelengths at which the fluorescence is measured in the microfluorometric assay for PKU
360 nm and 530 nm
wavelengths at which the fluorescence is measured in the microfluorometric assay for PKU
360 nm and 530m,
Reference method for quantitative serum phenylalanine
HPLC
Used in screening for inherited disorders in newborns
ms/ms
Amino acids are extracted from neonatal blood
samples and rapidly derived with N,Obis (trimethylsilyl)-trifluoroacetamide under microwave irradiation.
Microwave-assisted silylation followed by gas chromatography–mass spectrometry (GC/MS):
what is the purpose of silylation?
to increase the stability of the analyte and improve the gas chromatography behavior
silylating agent used in Microwave-assisted silylation followed by gas chromatography–mass spectrometry (GC/MS):
N,Obis(trimethylsilyl)-trifluoroacetamide
characterized by the excretion of tyrosine and tyrosine catabolites in urine
tyrosinemia
give the enzymes deficient in the 3 types of Tyrosinemia
Type 1: fumarylacetoacetate hydrolase
Type 2: tyrosine aminotransferase
Type 3: 4-hydroxyphenylpyruvate dioxygenase
diagnostic criteria for tyrosinemia?
- increased tyrosine level detected using ms/ms
- confirmatory test for elevated level of succinylacetone
color of urine sample in ferric chloride tube test for tyrosinemia
transient green color
color of urine sample in nitroso-naphthol test for tyrosinemia?
orange red color
drug treatment for tyrosinemia
nitisinone
action of nitisinone as a drug treatment for tyrosinemia?
Prevents the formation of malylacetoacetic acid
and fumarylacetoacetic acid which can be
converted to succinylacetone
treatment for tyrosinemia?
- low protein diet
- nitisione
- partial or full liver transplant
- most severe form of tyrosinemia
- Failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, distended abdomen, swelling
of legs, and increased predisposition for bleeding - Can lead to liver and kidney failure, nervous system problems, and an increased risk of cirrhosis or liver cancer later in life
type 1
- tyrosinemia that occurs in 1 in every 250,000 births
- Mental retardation and have symptoms of
excessive tearing, photophobia, eye pain and redness, and painful skin lesions on the palms and soles of the feet
type II
Mild mental retardation, seizures, and periodic
loss of balance and coordination
type III tyrosinemia
enzyme deficient in alkaptonuria?
homogentisate oxidase
Significant manifestation of alkaptonuria
Patient’s urine turns brownish-black when it mixes with air
indicate the color manifested in urine sample for the ff tests for alkaptonuria:
- Ferric chloride tube test
- Clinitest
- Homogentisic acid test
- Ferric chloride tube test - deep blue (Strasinger) / black (Bishop)
- Clinitest - yellow precipitate
- Homogentisic acid test - black
treatment for alkaptonuria?
high dose of vitamin C
enzyme deficient in MSUD?
a-ketoacid decarboxylase
odor of urine in msud?
maple syrup or burnt sugar odor of urine
in msud, what are the 3 branched-chain amino acids whose metabolism is blocked?
leucine
isoleucine
valine
