Proteins and Amino Acids

what aminoacidopathy refers to a mutation in the PAH gene?

PKU

what enzyme does the PAH gene encode?

phenylalanine hydroxylase

newborn testing of which aminoacidopathy is required in the U.S.?

PKU

for PKU, metabolites such as phenylpyruvic acid, phenylpyruvate, and phenyllactic acid can cause significant and permanent ____ damage.

brain

for PKU, increased phenylalanine and metabolites in urine can cause a musty or ____ odor.

mousy

PKU testing is done on all newborns at day _____ after birth.

3

the guthrie test for PKU utilizes a plate that contains _____, an antagonist to the growth of spores of bacillus subtilis.

beta2-thienylalanine

in the guthrie test for PKU, increased phenylalanine will inhibit action of _____ so the spores of bacillus subtilis will grow.

beta2-thienylalanine

PKU testing via the guthrie test can detect up to ____mg/dL

3

what form of PKU testing refers to a ferric chloride reaction that is positive in UA with a blue-grey to green reaction (may be not detect early in disease)?

phenistix

what aminoacidopathy refers to excess tyrosine in blood that causes an overflow of tyrosine in urine (cabbage-like odor)?

tyrosinemia

which type of tyrosinemia refers to a mutation in the FAH gene?

1

which type of tyrosinemia refers to a mutation in the TAT gene?

2

which type of tyrosinemia refers to a mutation in the HPD gene?

3

which type of tyrosinemia is best described:

• most severe

• severe liver disease

• cirrhosis

• liver cancer risk later in life

1

which type of tyrosinemia is best described:

• impaired mental development

• painful skin lesions

• photophobia

2

which type of tyrosinemia is best described:

• impaired mental development

• seizures

• loss of balance

3

in tyrosinemia, there will be an increase in tyrosine and _____ in the blood.

succinylacetone

the nitrosonaphthol test for tyrosinemia will result in a positive ____ color.

red

____ crystals appear as fine silky needles arranged in sheaves or bundles in acid urine.

tyrosine

tyrosine crystals are commonly present in tyrosinemia. true or false?

false

in liver disease, tyrosine crystals may appear together with _____ crystals.

leucine

tyrosine crystals should NOT be confused with crystals caused by ____.

x-ray dye

_____ will cause urine specific gravity to be greatly increased (1.040 → biologically impossible).

x-ray dye

____ crystals are soluble in alkali or dilute mineral acid.

tyrosine

what aminoacidopathy refers to a mutation in the HGD gene?

alkaptonuria

the HGD gene encodes the enzyme _____ to metabolize homogentisic acid in the phe/tyr pathway.

homogentisate oxidase

patients with ____ develop dark blue brown to black pigmentation in cartilage and connective tissue and arthritis.

alkaptonuria

urine darkens (may turn black) upon standing at room temperature or at alkaline pH in which aminoacidopathy?

alkaptonuria

what aminoacidopathy refers to the absence or extremely low activity of a complex of enzymes known as branched-chain alpha-ketoacid dehydrogenase (BCKD)?

MSUD

in MSUD, the normal metabolism of the three essential branched-chain amino acids by BCKD is stopped. what are the 3 amino acids?

leucine, isoleucine, valine

the most striking feature of ____ is the “burnt sugar” smell of urine, sweat, and breath.

MSUD

what aminoacidopathy is marked by severe neonatal vomiting, acidosis, seizures, stupor, failure to thrive, mental retardation and if undiagnosed can lead to death?

MSUD

for MSUD, the modified guthrie test includes agar that contains the inhibitor _____ which blocks growth of bacillus subtilis.

4-azaleucine

in MSUD, in the presence of _____ (leached from newborn’s blood disk), bacteria will grow for the modified guthrie test.

branched chain amino acids

for the microfluorometric assay for MSUD testing, leucine levels of greater than ____ g/dL are indicative of MSUD.

4

a prenatal diagnosis of MSUD can be made through decarboxylase enzyme concentration in cells cultured from _____.

amniotic fluid

the most common form of homocystinuria is caused by a mutation in the ____ gene.

CBS

the CBS gene encodes the enzyme _____ which is necessary for methionine metabolism.

cystathionine beta-synthase

enzyme deficiency in homocystinuria leads to elevated levels of homocysteine and ____.

methionine

newbornes with homocystinuria show no clinical effect but in late childhood develop _____, mental retardation, and ocular damage.

vascular thrombosis

the modified guthrie test can be used for homocystinuria where the inhibitor is _____.

L-methionine sulfoximine

a methionine concentration of greater than ____ mg/dL indicates homocystinuria.

2

cystinuria or cystinosis: defective reabsorption of cystine and dibasic amino acids?

cystinuria

cystinuria or cystinosis: renal stones develop in long history cases?

cystinuria

cystinuria or cystinosis: cystine crystals in urine are diagnostic?

cystinuria

cystinuria or cystinosis: true inborn error of metabolism?

cystinosis

cystinuria or cystinosis: increased cystine in cornea, bone marrow, lymph nodes, and internal organs?

cystinosis

cystinuria or cystinosis: fanconi’s syndrome develops with renal failure?

cystinosis

blood should be collected at least after _____ hours of fasting to avoid the effects of absorbed amino acids from diet.

6-8

for amino acid analysis, _____ plasma separated from cells immediately to avoid the smallest contamination of cells.

heparinized

hemolysis must be avoided for amino acid analysis samples. true or false?

true

deproteinization should be performed within ____ minutes of sample collection for amino acid analysis.

30

if analysis of amino acids cannot be performed immediately, the sample should be frozen at ____°C.

-20 to -40°C

urine can be random collection for screening purposes of amino acid analysis. true or false?

true

for quantitation of amino acids, a 24-hour urine specimen preserved with ____ or organic solvents is required.

thymol

in electrophoresis, which fraction contains the following:

• alpha anti-trysin

• alpha acid glycoprotein

alpha1-antitrypsin

in electrophoresis, which fraction contains the following:

• alpha3 macroglobulin

• haptoglobin

alpha2-macroglobulin

in electrophoresis, which fraction contains the following:

• hemopexin

• transferrin

• beta lipoproein

• complement C3

beta

in electrophoresis, which fraction contains the following:

• IgM

• IgG

• IgA

gamma

reference range of total protein.

6-8 g/dL

albumin reference range.

3.5-5.0 g/dL

globulin reference range.

1.8-4.5 g/dL

what is the range for A/G ratio?

1.3:1 to 1.8:1

how to calculate globulin?

total protein - albumin

____ (hypo) proteins is associated with:

• urinary loss

• liver and GI disorders

• malnutrition

• immunodeficiencies

• burns

decreased

____ (hyper) proteins is associated with:

• dehydration

• inflammation

• gammopathies

increased

alpha 1 globulin reference interval.

0.15-0.31 g/dL

alpha 2 globulin reference interval.

0.46-0.90 g/dL

beta globulin reference interval.

0.62-1.14 g/dL

gamma globulin reference interval.

0.60-1.70 g/dL

prealbumin will be a thick/strong band on SPE. true or false?

false

____ is associated with the following:

• precedes albumin (anodal)

• binds thyroxine (TBP)

• transthyretin

• retinol (vitamin A) binding protein

prealbumin

prealbumin has a thick/strong band on CSF electrophoresis. true or false?

true

_____ can assess nutrition status (half life of 2-3 days) and is increased in positive nitrogen balance seen with parenteral nutrition.

prealbumin

what protein electrophoresis fraction is responsible for 80% of colloidal oncotic pressure intravascular?

albumin

what protein electrophoresis fraction:

• transport surface

• serves as a source/reserve of amino acids

• serves as a plasma buffer

• provides antioxidant activity

• alters capillary permeability

albumin

albumin is _____ in renal and liver pathology.

decreased

albumin is ____ in malnutrition, impaired absorption/digestion, and inflammation.

albumin

albumin is ____ in dehydration.

increased

____ can be falsely increased when a tourniquet is left on too long or the specimen is allowed to evaporate.

albumin

what protein electrophoresis fraction is a serpin (serine protease inhibitor) that binds to and inactivates trypsin?

alpha1-antitrypsin

deficiency in ____ is associated with the following:

• pulmonary emphysema [Pi(null) allele or ZZ phenotype]

  • degradation of elastin in alveoli by neutrophil elastase

• cirrhosis (neonatal)

• hepatocellular carcinoma

alpha1-antitrypsin

alpha1-antitrypsin is _____ with inflammation (acute phase response) and estrogen increase.

increased

what protein electrophoresis fraction is the largest non-immunoglobulin in plasma?

alpha2-macroglobulin

what protein electrophoresis fraction is a protease inhibitor: inhibition of enzymes in the kinase, complement, coagulation and fibrinolytic systems?

alpha2-macroglobulin

alpha2-macroglobulin is _____ in nephrotic syndrome.

increased

alpha2-macroglobulin is _____ in acute pancreatitis.

decreased

which alpha2-macroglobulin protein refers to:

• copper transport protein

• levels fluctuate with variety of physiological states

  • measurement is used to screen for wilson’s disease

ceruloplasmin

which alpha2-macroglobulin protein refers to:

• binds to and preserves hemoglobin

• involved in inflammatory response

haptoglobin

hemolytic diseases can deplete haptoglobin. true or false?

true

C3 and C4 can migrate in the ____ region of SPE.

beta

complement is ____ in genetic deficiencies.

decreased

complement is ____ in inflammation.

increased

_____ is found on the surface of most nucleated cells, high in lymphocytes.

beta2-microglobulin

____ is high in inflammatory disorders RA and SLE from impaired renal tubular clearance.

beta2-microglobulin

which serum protein of the beta fraction is involved with iron transport and is increased in IDA?

transferrin

____ is only present in SPE when plasma is used or an incomplete clot → beta/gamma interface

fibrinogen

what is the most sensitive indicator of acute phase reactant (trauma, inflammation, infection, etc.)?

CRP

a single sharp peak in the gamma region indicates a paraprotein associated with a monoclonal gammopathy (multiple myeloma) → _____.

M protein