Step1_Biochemistry Flashcards
_______ disease is caused by a deficiency in α-galactosidase A.
Fabry
Fabry disease is caused by a deficiency in _______
α-galactosidase A.
________ disease is caused by a deficiency in glucocerebrosidase (β-glucosidase).
Gaucher.
leads to an accumulation of glucocerebroside.
treatment for Gaucher disease is recombinant glucocerebrosidase.
Gaucher disease is caused by a deficiency in ____________
glucocerebrosidase (β-glucosidase).
leads to an accumulation of glucocerebroside.
treatment for Gaucher disease is recombinant glucocerebrosidase.
___________ disease is caused by a deficiency in sphingomyelinase.
Niemann-Pick
Niemann-Pick disease is caused by a deficiency in ___________.
sphingomyelinase
________ disease is caused by a deficiency in hexosaminidase.
Tay-Sachs.
This leads to the accumulation of GM2 gangliosides.
Tay-Sachs disease is caused by a deficiency in ____________.
hexosaminidase A.
This leads to the accumulation of GM2 gangliosides.
“Gargoylism”, a somewhat outdated term that refers to the physical features typical of ________ syndrome: clawed hands and thick, coarse facial features with a low nasal bridge)
Hurler syndrome
What enzyme catalyzes hydrolysis of arginine to yield urea and regenerate ornithine?
Arginase I
All lysosomal storage disorders are autosomal recessive, EXCEPT: (2)
Fabry’s disease.
Hunter’s syndrome.
These are X-linked recessive.
What is the RDS step of the Urea cycle?
The first step, the conversion of CO2 and ammonia to carbamoyl phosphate.
Enzyme: carbamoyl phosphate synthetase I
Obligate activator: N-acetyl-glutamate
________ Disease has a deficiency in galactocerebrosidase (galactocerebroside β-galactosidase). This leads to an accumulation of galactocerebroside and psychosine.
Krabbe disease
Krabbe Disease has a deficiency in what enzyme?
Krabbe Disease has a deficiency in galactocerebrosidase (galactocerebroside β-galactosidase). This leads to an accumulation of galactocerebroside and psychosine.
Cherry-red spots on the macula is ~w/ what lysosomal storage disease?
Niemann-Pick
____________ is the enzyme that converts tyrosine to the L isomer of Di-hydrOxy-PhenylAlanine (or L-DOPA, often just referred to as DOPA).
Tyrosine hydroxylase.
THB (tetrahydrobiopterin) is a necessary cofactor for the enzyme tyrosine hydroxylase. THB is also a cofactor for phenylalanine hydroxylase.
Tyrosine is a precursor for many important molecules such as:
(4)
Epinephrine and norepinephrine
Dopamine
Melanin
Thyroid hormones
____________ cells are abnormal nucleated erythroblasts that have iron granules accumulated in perinuclear mitochondria (seen as “constellations” around the nucleus with Prussian Blue stain.)
Sideroblasts
Phenylketonuria (PKU) is caused by autosomal recessive defects in the enzyme _______________.
phenylalanine hydroxylase (PAH)
______________ is an autosomal dominant defect of UROD (uroporphyrinogen decarboxylase).
Porphyria cutanea tarda
What is the cell does heme synthesis occur?
he first step and last 3 steps of heme synthesis occur in mitochondria, the rest occur in the cytosol.
What is the Tx of Acute Intermittent Porphyria?
glucose and heme in order to inhibit ALA synthase. This bypasses the defective heme synthesis pathway.
_____________anemia is the most common genetic cause of sideroblastic anemia and results from a defect in the ALA synthase-2 gene.
X-linked sideroblastic
n acute intermittent porphyria, what product accumulates and episodically becomes symptomatic.
porphobilinogen
What heme synthesis product is elevated in porphyria cutanea tarda, but this affects the skin (blistering) and lacks the GI and neurologic effects.
Uroporphyrinogen III
Microcytic anemia combined with elevated serum lead level indicates lead poisoning. Lead poisoning is also characterized by RBCs showing ______________. Lead inhibits two heme pathway enzymes: aminolevulinic acid dehydratase and ferrochelatase.
basophilic stippling
Microcytic anemia combined with elevated serum lead level indicates lead poisoning. Lead poisoning is also characterized by RBCs showing basophilic stippling. Lead inhibits what two heme pathway enzymes?
Lead inhibits two heme pathway enzymes:
aminolevulinic acid (ALA) dehydratase
ferrochelatase.
Pt. with Mouse like order or musty odor, think?
phenylketonuria.
The defective enzyme is phenylalanine hydroxylase, which requires tetrahydrobiopterin as a cofactor. The mousy odor is due to phenylacetate, a metabolic product of Phe. The other answer choices are cofactors in several other reactions.
What disease is Caused by a defective phosphotransferase enzyme which leads to the inability to properly synthesize the mannose-6-phosphate tag required for targeting enzymes to lysosomes?
Where do the high level of enzymes build up?
I-cell disease!
high levels of lysosomal enzymes build up in the extracellular space.
Tyr is synthesized from Phe using what enzyme?
Tyr is synthesized from Phe using the enzyme phenylalanine hydroxylase. This is important to remember because phenylalanine hydroxylase deficiency causes phenylketonuria. Moreover, tyrosine is a precursor for:
catecholamines
several neurotransmitters (DOPA)
melanin and thyroid hormones
_____________ is a very rare inherited zinc deficiency caused by mutations in a gene.
Acrodermatitis enteropathica is a very rare inherited zinc deficiency caused by mutations in a gene that encodes a zinc transporter in the small intestine.
In patients with PKU, what amino acid becomes an essential amino acid since it cannot be created from phenylalanine
tyrosine
NADPH is used to reduce _____________, which is a coenzyme for glutathione peroxidase which prevents oxidative damage by converting H2O2 → H2O. This is especially important in RBCs.
glutathione
Both phases of the HMP shunt occur in cytosol.
NADPH is used to reduce glutathione [GSSG (oxidized) → GSH (reduced)], which is a coenzyme for _________________ which prevents oxidative damage by converting H2O2 → H2O. This is especially important in RBCs.
glutathione peroxidase
Both phases of the HMP shunt occur in cytosol.
S/Sx
- child with pain in hands and feet.
- lack of sweat
- skin findings
Fabry’s Disease [X-linked]
def. in alpha-galactosidase A
accumulation of ceramide trihexoside.
What immune cell is abnormal in Gaucher disease?
Macrophages “crinkle paper”
Jewish Kid with splenomegaly, anemia, bruising, joint pain == ?
Gaucher disease [AR]
def. in glucocerebrosidase
accum: glucocerebroside
macrophages with lipid “foam cells” ==?
Niemann-pick
Niemann-pick eye finding?
Cherry red spot
S/Sx:
- previously well child
- weakness, loss of motor func.
- cherry red spot on eye
- enlarged liver of spleen
???
Niemann pick disease
def. in sphinomyelinase
accum: sphinomyelin
What are Sx of anti-cholinergic toxicity and what type of acid-base disturbance is it associated with?
Fever, altered mental status, tachycardia
NOT ~w/ significant acid-base disturbance.
Anything that causes hyperventilation will produce what type of acid-base disturbance?
Respiratory Alkalosis.
ex: anxiety, hypoxemia, salicylate toxicity, pressure or trauma to the respiratory center.
a defect in the enzyme cystathionine beta-synthase results in elevated levels of the amino acid homocysteine is called?
Homocystinuria
How does Betatine work in the Tx of Homocystinuria?
Betaine decreases the concentration of homocysteine, by promoting the conversion of homocysteine to methionine.
Phenylalanine is an intermediate in the synthesis of ____________.
Phenylalanine is an intermediate in the synthesis of catecholamines. In the disease Phenylalanine accumulates in the disease phenylketonuria, which is caused by a defect in phenylalanine hydroxylase.
In ornithine transcarbamylase deficiency, there is a defect in what enzyme?
Orotic acid increases with defects in the Urea Cycle. In ornithine transcarbamylase deficiency, there is a defect in the enzyme ornithing transcarbamylase. Carbamylphosphate cannot be converted to citrulline and so is shunted to orotic acid.
there is a decrease in citruline.
type III dyslipoproteinemia or dysbetalipoproteinemia, which is characterized by high levels of cholesterol and triglycerides in the bloodstream carried by intermediate density lipoproteins (IDL) and chylomicrons. The disease predisposes patients to early atherosclerosis and cardiovascular disease.
Type III dyslipoproteinemia is caused by a mutation in the genes that code for _______________
apolipoprotein E (ApoE)
What is the normal actions of ApoE and what happens fi ApoE is mutated?
ApoE is a protein that mediates cellular uptake (and hence bloodstream removal) of triglyceride-rich IDL and chylomicron remnants. Lack of ApoE leads to the inability of chylomicrons and IDL to be cleared from the blood, leading to increased serum cholesterol and triglycerides and decreased serum high density lipoprotein (HDL.
Patients with dysbetalipoproteinemia present with tuberoeruptive xanthomas (firm, nontender yellow-orange nodules along extensor surfaces), and commonly have premature heart disease and peripheral vascular disease.
The urine sample from a patient turns black when allowed to stand. The patient has no known health issues, and a blood smear shows normal findings.
What product is likely elevated in the patient’s urine?
Homogentisate
Urine turning black when left standing is a defining feature of __________.
alkaptonuria
alkaptonuria is a defect in what enzyme?
homogentisate dioxygenase results in a build-up of homogentisate.
Normally tyrosine is degraded to fumarate, with homogentisate being an intermediate in this pathway. The most serious complication is a potential for joint disease later in life.
What are echinocytes?
a form of red blood cell that has an abnormal cell membrane characterized by many small, evenly spaced thorny projections.
A more common term for these cells is burr cells.