Step1_Biochemistry Flashcards
1
Q
_______ disease is caused by a deficiency in α-galactosidase A.
A
Fabry
2
Q
Fabry disease is caused by a deficiency in _______
A
α-galactosidase A.
3
Q
________ disease is caused by a deficiency in glucocerebrosidase (β-glucosidase).
A
Gaucher.
leads to an accumulation of glucocerebroside.
treatment for Gaucher disease is recombinant glucocerebrosidase.
4
Q
Gaucher disease is caused by a deficiency in ____________
A
glucocerebrosidase (β-glucosidase).
leads to an accumulation of glucocerebroside.
treatment for Gaucher disease is recombinant glucocerebrosidase.
5
Q
___________ disease is caused by a deficiency in sphingomyelinase.
A
Niemann-Pick
6
Q
Niemann-Pick disease is caused by a deficiency in ___________.
A
sphingomyelinase
7
Q
________ disease is caused by a deficiency in hexosaminidase.
A
Tay-Sachs.
This leads to the accumulation of GM2 gangliosides.
8
Q
Tay-Sachs disease is caused by a deficiency in ____________.
A
hexosaminidase A.
This leads to the accumulation of GM2 gangliosides.
9
Q
“Gargoylism”, a somewhat outdated term that refers to the physical features typical of ________ syndrome: clawed hands and thick, coarse facial features with a low nasal bridge)
A
Hurler syndrome
10
Q
What enzyme catalyzes hydrolysis of arginine to yield urea and regenerate ornithine?
A
Arginase I
11
Q
All lysosomal storage disorders are autosomal recessive, EXCEPT: (2)
A
Fabry’s disease.
Hunter’s syndrome.
These are X-linked recessive.
12
Q
What is the RDS step of the Urea cycle?
A
The first step, the conversion of CO2 and ammonia to carbamoyl phosphate.
Enzyme: carbamoyl phosphate synthetase I
Obligate activator: N-acetyl-glutamate
13
Q
________ Disease has a deficiency in galactocerebrosidase (galactocerebroside β-galactosidase). This leads to an accumulation of galactocerebroside and psychosine.
A
Krabbe disease
14
Q
Krabbe Disease has a deficiency in what enzyme?
A
Krabbe Disease has a deficiency in galactocerebrosidase (galactocerebroside β-galactosidase). This leads to an accumulation of galactocerebroside and psychosine.
15
Q
Cherry-red spots on the macula is ~w/ what lysosomal storage disease?
A
Niemann-Pick
16
Q
____________ is the enzyme that converts tyrosine to the L isomer of Di-hydrOxy-PhenylAlanine (or L-DOPA, often just referred to as DOPA).
A
Tyrosine hydroxylase.
THB (tetrahydrobiopterin) is a necessary cofactor for the enzyme tyrosine hydroxylase. THB is also a cofactor for phenylalanine hydroxylase.
17
Q
Tyrosine is a precursor for many important molecules such as:
(4)
A
Epinephrine and norepinephrine
Dopamine
Melanin
Thyroid hormones
18
Q
____________ cells are abnormal nucleated erythroblasts that have iron granules accumulated in perinuclear mitochondria (seen as “constellations” around the nucleus with Prussian Blue stain.)
A
Sideroblasts
19
Q
Phenylketonuria (PKU) is caused by autosomal recessive defects in the enzyme _______________.
A
phenylalanine hydroxylase (PAH)
20
Q
______________ is an autosomal dominant defect of UROD (uroporphyrinogen decarboxylase).
A
Porphyria cutanea tarda
21
Q
What is the cell does heme synthesis occur?
A
he first step and last 3 steps of heme synthesis occur in mitochondria, the rest occur in the cytosol.
22
Q
What is the Tx of Acute Intermittent Porphyria?
A
glucose and heme in order to inhibit ALA synthase. This bypasses the defective heme synthesis pathway.
23
Q
_____________anemia is the most common genetic cause of sideroblastic anemia and results from a defect in the ALA synthase-2 gene.
A
X-linked sideroblastic
24
Q
n acute intermittent porphyria, what product accumulates and episodically becomes symptomatic.
A
porphobilinogen
25
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
26
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
27
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.
28
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.
29
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.
30
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
31
_____________ 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.
32
In patients with PKU, what amino acid becomes an essential amino acid since it cannot be created from phenylalanine
tyrosine
33
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.
34
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.
35
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.
36
What immune cell is abnormal in Gaucher disease?
Macrophages "crinkle paper"
37
Jewish Kid with splenomegaly, anemia, bruising, joint pain == ?
Gaucher disease [AR]
def. in glucocerebrosidase
accum: glucocerebroside
38
macrophages with lipid "foam cells" ==?
Niemann-pick
39
Niemann-pick eye finding?
Cherry red spot
40
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
41
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.
42
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.
43
a defect in the enzyme cystathionine beta-synthase results in elevated levels of the amino acid homocysteine is called?
Homocystinuria
44
How does Betatine work in the Tx of Homocystinuria?
Betaine decreases the concentration of homocysteine, by promoting the conversion of homocysteine to methionine.
45
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.
46
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.
47
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)
48
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.
49
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
50
Urine turning black when left standing is a defining feature of __________.
alkaptonuria
51
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.
52
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.
53
How do Patients with PK deficiency typically have increased tolerance to anemia?
In the glycolysis pathway, PK is downstream from the step in which the metabolic intermediate, 2,3-bisphosphoglycerate (2,3-BPG), is formed. Increased 2,3-BPG levels cause a rightward shift of the oxygen dissociation curve. Decreased activity of PK causes 2,3-BPG to accumulate. This results in a rightward shift of the oxygen dissociation curve for hemoglobin in patients with PK deficiency. The rightward shift leads to better oxygen delivery to the tissues and superior tolerance for anemia.
54
what do Pilocytic astrocytoma stain positive for?
Glial Fibrillary Acidic Protein (GFAP).
All astrocytes stain (+)GFAP.
55
What are Pilocytic astrocytomas?
Pilocytic astrocytomas are slow growing, well-demarcated tumors that occur predominantly in children and young adults.
Pilocytic astrocytomas often arise in the cerebellar hemispheres and around the third ventricle.
Tumors often have a cystic component that enhance on CT and MRI due to the vascularity of the tumor.
Microscopically, pilocytic astrocytomas have cell cytoplasm that stain for glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed by numerous cell types in the central nervous system such as astrocytes.
56
Pilocytic astrocytomas arise where in the brain?
Pilocytic astrocytomas often arise in the cerebellar hemispheres and around the third ventricle.
57
What is Williams Syndrome?
Williams syndrome is a genetic disorder resulting from the deletion of approximately 26 genes from chromosome 7q11.23. The majority of cases are due to random event at fertilization. One of the deleted genes is ELN, encoding the protein elastin, which may contribute to many of the symptoms.
58
What are some S/Sx of Williams Syndrome?
Williams syndrome has a variable clinical presentation. Typical facial features include “elf-like” characteristics such as wide mouth, full lips, short flat nose, and full cheeks. Most patients show mild to moderate intellectual disability. Emotionally, a notable feature of Williams syndrome is their high sociability and empathy. Supravalvular aortic stenosis may be seen as well.
In Williams syndrome, there may be increased sensitivity to vitamin D, resulting in hypercalcemia.
59
One of the nitrogen groups found in urea is provided by ammonia, and the other is provided by aspartate. What metabolic process directly provides aspartate to the urea cycle?
TCA cycle (Citric acid cycle)
60
Respiratory burst is an essential step for which of the following events in an acute inflammatory response?
Generation of Microbicidal Activity
61
What is the Taut form of hemoglobin? Where in the body do you see it?
The taut form has a low affinity for oxygen, whereas the relaxed form has a high affinity for O2 (300 times higher).
deoxyhemoglobin is more tense (taut), so you would see it in muscles/tissues
62
Hemoglobin is more likely in the RELAXED form where in the body?
in the lungs
63
What is the only polymerase with 5' --> 3' exonuclease activity?
DNA pol 1
64
If a male and a female are affected in the bottom generation → ??
the disease is not X-linked
65
Neither of the parents have the disease phenotype → the disease is not ???
disease cannot be autosomal dominant, X-linked dominant, or codominant
66
the main prokaryotic polymerase = ?
DNA Pol III
67
N-linked glycosylation occurs in the ___________
rough ER
68
retrograde transport of vesicles: from trans-Golgi network (TGN) to cis-Golgi network (CGN) and from the cis-Golgi network to rER;
due to ???
COPI
"COPi goes Inwards"
69
What enzyme converts glucose-6-phosphate to glucose in gluconeogenesis, and where is it found?
Glucose-6-phosphatase
on the membrane of the smooth endoplasmic reticulum.
70
List XLR disorders:
```
Bruton Agammaglobulinemia
Wiskott-Aldrich
Fabry disease
G6PD deficiency
Ocular albinism
Note: Oculocutaneous albinism is different than ocular albinism. Oculocutaneous albinism is cau
```
71
Arsenic poisoning interferes with enzymes that use what cofactor?
lipoic acid cofactor;
Tender Care And Love For Nancy Enzymes
72
Arsenic poisoning interferes with lipoic acid cofactor containing enzymes; what are they? (3)
pyruvate dehydrogenase complex (PDC)
α-ketoglutarate dehydrogenase
branched-chain α-keto acid dehydrogenase.
73
increase in serum alanine & increase in lactic acid == > what enzyme def.???
pyruvate dehydrogenase complex (PDC)
increase in serum alanine via alanine aminotransferase.
+ neurological signs
74
all daughter of affected father are affected ==> what mode of inheritance?
X-linked Dominant
No father-to-son transmission.
75
No father-to-son transmission ==> what mode of inheritance?
X-linked recessive.
sons of heterozygous mothers have a 50% chance of being affected.
76
Key histological features of the brain seen with pyruvate dehydrogenase deficiency include
gray matter degeneration with brainstem necrosis and capillary proliferation.
77
________ directs vesicles from the trans-Golgi network (TGN) to lysosomes.
Clathrin
78
Clathrin is also involved in the formation of vesicles during ???
endocytosis (receptor-mediated endocytosis).
79
The PDC is activated by ????
pyruvate
NAD+
ADP
Ca2+
Low-energy state
80
The PDC is inhibited by ???
ATP, acetyl-CoA, and NADH.
| high Energy State
81
Termination of eukaryotic translation requires what?
protein release factors binding to stop codons, which release the polypeptide from the ribosome and cause the ribosomal subunits to dissociate
82
Prokaryotic DNA polymerases with 3′ → 5′ exonuclease activity include: (3)
DNA polymerase I
DNA polymerase II
DNA polymerase III
In contrast, DNA polymerase I is the only prokaryotic polymerase with 5′ → 3′ exonuclease activity.
83
Initiator tRNA is the only tRNA that can bind to what site?
Initiator tRNA is the only tRNA that can bind to the P-site; all others bind to A-site.
84
All daughters of a male with an _____________ disorder will inherit the disease-causing mutation.
X-linked dominant
85
A family pedigree showing only affected males and no affected females suggests what mode of inheritance?
XLR
affected Pt.'s parents are unaffected and most people affected are Males
86
Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than or equal to _____ mmHg at rest.
25 mm Hg
87
Familial hypercholesterolemia is an _____________ condition due to mutations in the gene encoding the receptor for low-density lipoprotein (LDL)
autosomal dominant
88
Familial hypercholesterolemia is an autosomal dominant condition due to mutations in the gene encoding the receptor for ________________
low-density lipoprotein (LDL)
89
Bilateral acoustic neuromas
+
neurofibromas, meningiomas, gliomas, and schwannomas of cranial and spinal nerves
=== ???
Neurofibromatosis type 2 (NF2)
90
Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger == > what trisomy?
Trisomy 18
91
multiple congenital anomalies, including clenched fist with overlapping fingers, prominent occiput, inward turning "rocker-bottom" feet, congenital heart defects, low-set ears, micrognathia, and severe intellectual disability.
what trisomy?
18
92
```
Testicular atrophy
High-pitched voice
Gynecomastia
Hypogonadism
Infertility is common
Low Testosterone
Elevated FSH and LH
```
==> ?
Klinefelter syndrome; 47, XXY
93
mental retardation, simian crease (a single transverse palmar crease), duodenal atresia and congenital heart disease ===> ???
trisomy 21
94
long and narrow face with prominent forehead and chin, large ears, and testicular enlargement ==> ???
Fragile X syndrome (X-linked dominant disease) is the most common inherited cause of mental retardation.
CGG triNuc expansion.
95
In ____________________ inheritance, both male-to-male and female-to-male transmission are present, and multiple generations are affected, except in cases of incomplete penetrance.
autosomal dominant
96
______________ syndrome, sometimes called the "happy puppet syndrome", is associated with severe developmental delay, especially in language acquisition, and an ataxia.
Angelman
97
Cri-du-chat syndrome is due to a terminal deletion of the short arm of what chromosome? and what is a common additional finding?
Chr. 5
VSD
98
Wilms Tumor, also known as nephroblastoma, is associated with the WT1 gene mutation, located on the short arm of what chromosome?
chromosome 11.
99
____________ disease is caused by a mutation in the gene that encodes the lysosomal enzyme hexosaminidase A (HEXA).
It is inheritated in _________
Tay-Sachs
Autosomal recessive
100
_____1_____ is an _____2_____ disorder generally characterized by a defect in the tyrosinase enzyme, resulting in an inability to produce melanin.
1. Albanism
| 2. autosomal recessive
101
_____________ syndrome results from a deletion at a specific gene locus on the paternally derived chromosome 15 that is imprinted on the maternally derived chromosome 15.
Prader-Willi
102
If the embryo contains two or more X chromosomes, the extra ones will be inactivated until only one X chromosome remains active in a given cell line.
This is called what?
Barr Bodies.
47, XXY
103
define: Pleiotrophy
Pleiotrophy refers to the multiple, often unrelated phenotypic effects from a mutation within a single gene.
104
__________ refers to the multiple, often unrelated phenotypic effects from a mutation within a single gene.
Pleiotrophy
example of this is albinism, in which a single gene defect affects pigmentation but also can present with visual problems as well.
105
Define: locus heterogeneity
refers to mutations at different gene loci resulting in the same phenotype
106
Hemophilia A and B are due to mutations in clotting factors VIII and IX, respectively.
What is their mode of inheritance?
X-linked recessive diseases
107
For ________________ disorders, all of the daughters of an affected male will be carriers.
X-linked recessive
108
In _______________ diseases, carrier mothers pass the disease to half their sons.
In X-linked recessive diseases, carrier mothers pass the disease to half their sons.
Affected fathers can have carrier daughters, but their sons will not be affected.
109
Both orotic aciduria and ornithine transcarbamylase deficiency present with elevated levels of orotic acid, however, they can be differentiated by the presence of hyperammonemia, which is exclusive to which deficiency?
ornithine transcarbamylase deficiency
110
Defect in what enzyme can lead to Orotic aciduria?
Orotic aciduria is caused by an autosomal recessive defect in UMP synthase.
111
What enzyme does NOT play a role in Base Excision repair of DNA?
DNA polymerase delta.
112
UMP synthase deficiency (aka hereditary orotic aciduria) leads to ???
an inability to convert orotic acid to UMP during pyrimidine synthesis. This results in orotic aciduria.
113
What toxin inhibits RNA polymerase II?
α-amanitin is a toxin found in Amanita phalloides (deadly toxin found in certain mushrooms). It inhibits RNA polymerase II and can cause liver damage when ingested.
114
Antibodies directed against U1 RNP (ribonucleoprotein) are associated with what disease.
mixed connective tissue disease (MCTD).
115
What enzyme is required to metabolize chylomicrons and VLDL?
Lipoprotein Lipase (LPL)
116
what enzyme catalyzes the conversion of triglycerides in chylomicrons and VLDL to free fatty acids and glycerol.
Lipoprotein lipase
117
Deficiency of this enzyme would lead to elevated levels of chylomicrons (chylomicronemia) and VLDL.
Lipoprotein Lipase (LPL)
118
what carries dietary fats and VLDL carries predominantly fat that is synthesized in the liver.
Chylomicrons
119
What deficiency causes accumulation of C8–C10 acylcarnitines?
MCAD
Impairment of fatty acid beta-oxidation (which requires the MCAD enzyme) in the liver during fasting conditions results in low ATP levels.
120
MCAD deficiency results what changes?
MCAD deficiency results in fasting hypoglycemia and hypoketonemia.
Hypoglycemia results in glucagon secretion, which activates adipose lipolysis.
121
If tyrosine kinase activity is increased, several rate-limiting enzymes in what pathways will have increase activity?
anabolic pathways will have increased activity.
This is when insulin binds to its receptor, which is a tyrosine kinase.
122
What does insulin activity do to cAMP concentration?
Insulin DECREASES cAMP.
*** cAMP activates Protein Kinase A***
123
What enzyme is phosphorylated and activated by protein kinase A (PKA), an enzyme activated by glucagon; in the liver?
Glycogen phosphorylase kinase
124
Is hexokinase/Glucokinase regulated by Insulin?
FUCK to the hells NOOOOOO!!!
125
what are lipoproteins that primarily carry dietary triglycerides from the intestine to the tissues?
Chylomicrons
126
Lipoprotein lipase is the enzyme required for the metabolism of ____________ & ____________ and is specifically found on the luminal surface of endothelial cells lining the capillaries.
chylomicrons and VLDL
127
what enzyme is the enzyme required for the metabolism of chylomicrons and VLDL and is specifically found on the luminal surface of endothelial cells lining the capillaries?
Lipoprotein lipase
128
In diabetic ketoacidosis, the level of ______________ increases approximately 5 times the increase in acetoacetate.
3-hydroxybutyrate
in pathologic conditions such as poorly controlled diabetes and alcoholism, in which the concentration of NADH is high, the ratio shifts and 3-hydroxybutyrate predominates. Therefore, the ratio of acetoacetate to 3-hydroxybutyrate actually decreases, while the net amount of ketoacids increases.
129
what type of stone are specifically associated with excessive indirect bilirubin production, such as that which occurs in hemolytic anemias, including sickle cell anemia?
Calcium bilirubinate stones
130
Brown-Mixed stones arise from what?
Billiary Tract Infections
they are made up of:
varying degrees of cholesterol, calcium carbonate or palmitate, bilirubin, and calcium bilirubinate.
131
Where would you find Calcium oxalate stones and Cystine stones?
in the KIDNEY!!!
these are NOT gallstones.
