Module 3 Flashcards
(189 cards)
1
Q
I-cell disease affected enzyme (Dr. R)
A
N-Acetylglucosamine-1-phosphotransferase (missing mannose-6-phosphate tag)
2
Q
I-cell disease biomarker (Dr. R)
A
Elevated lysosomal enzymes in plasma (inclusion bodies)
3
Q
I-cell disease symptoms (Dr. R)
A
Coarse facial features
Developmental delay
Skeletal abnormalities
Restricted joint movement
Enlarged liver and spleen
4
Q
Gaucher disease affected enzyme (Dr. R)
A
Glucocerebrosidase
5
Q
Gaucher disease biomarker (Dr. R)
A
Elevated chitotriosidase
6
Q
Gaucher disease symptoms (Dr. R)
A
Enlarged liver and spleen
Bone pain
Fatigue
Bruising and bleeding
Lung disease
Growth retardation
7
Q
Fabry disease affected enzyme (Dr. R)
A
Alpha-galactosidase A
8
Q
Fabry disease biomarker (Dr. R)
A
Elevated globotriaosylceramide (ceramide trihexoside)
9
Q
Fabry disease symptoms (Dr. R)
A
Pain in hands and feet
Kidney problems
Heart issues
Angiokeratomas
Corneal opacities
Gastrointestinal problems
10
Q
Tay-Sachs disease affected enzyme (Dr. R)
A
Hexosaminidase A
11
Q
Tay-Sachs disease biomarker (Dr. R)
A
Elevated GM2 ganglioside
12
Q
Tay-Sachs disease symptoms (Dr. R)
A
Progressive neurological deterioration
Cherry-red spot-on macula
Seizures
Muscle weakness
Vision and hearing loss
Developmental delay
13
Q
Krabbe disease affected enzyme (Dr. R)
A
Galactocerebrosidase
14
Q
Krabbe disease biomarker (Dr. R)
A
Galactocerebroside, psychosine
15
Q
Krabbe disease symptoms (Dr. R)
A
Peripheral neuropathy
Destruction of oligodendrocytes
Developmental delay
Optic atrophy
Globoid cells
16
Q
Niemann-Pick disease affected enzyme (Dr. R)
A
Sphingomyelinase
17
Q
Niemann-Pick disease biomarker (Dr. R)
A
Elevated sphingomyelin
18
Q
Niemann-Pick disease symptoms (Dr. R)
A
Enlarged liver and spleen
Neurological decline
Ataxia
Interstitial lung disease
Feeding difficulties
Failure to thrive
19
Q
MLD affected enzyme (Dr. R)
A
Arylsulfatase A
20
Q
MLD biomarker (Dr. R)
A
Elevated sulfatides
21
Q
MLD symptoms (Dr. R)
A
Progressive neurological decline
Motor function loss
Behavioral changes
Seizures
Peripheral neuropathy
22
Q
Hurler syndrome affected enzymes (Dr. R)
A
Alpha-L-iduronidase
23
Q
Hurler syndrome biomarker (Dr. R)
A
Elevated dermatan sulfate and heparan sulfate
24
Q
Hurler syndrome symptoms (Dr. R)
A
Developmental delay
Skeletal abnormalities
Airway obstruction
Corneal clouding
Hepatosplenomegaly
25
Hunter syndrome affected enzymes (Dr. R)
Iduronate-2-sulfatase
26
Hunter syndrome biomarker (Dr. R)
Absence of plasma iduoronate-2-sulfatase
Elevated urinary glycosaminoglycan
27
Hunter syndrome symptoms (Dr. R)
Mild Hurler plus aggressive behavior
Hepatosplenomegaly
28
What is a sphingolipid
A lipid molecule with a long-chain or sphingoid base that may be linked to a fatty acid via an amide bond
29
What is a mucopolysaccharide
A polysaccharide formed by repeated disaccharides
30
Examples of mucopolysaccharide
Glycosaminoglycans (GAG's) (hyaluronic acid, chondroitin/dermatan/heparin/keratan sulfate)
Proteoglycans (aggrecan, decorin)
31
Examples of sphingolipids
Glycosylceramide
32
Non autosomal recessive LSD's
Fabry disease
Hunter syndrome
33
Sphingolipidosis diseases
Tay-Sachs (GM2 Type A)*
Sandhoff (GM2 Type O) Activator deficiency (GM2 Type AB)
Niemann-Pick (A, B, C)*
Gaucher (1, 2, 3)*
Fabry (Classic, Adult)*
Metachromatic leukodystrophy (MLD)*
Krabbe (Globoid leukodystrophy)*
GM1 gangliosidosis (1, 2, 3)
Multiple sulfatase deficiency
34
Oligosaccharide diseases
Alfa mannosidiosis
Schindler disease
Aspartylglusocaminuria
Fucosidosis
35
Mucopolysaccharidosis syndromes
Hurler*
Scheie
Hurler-Scheie
Hunter*
San Filippo (A, B, C, D)
Morquio (A, B)
Maroteaux-Lamy
Sly
36
Neuronal ceroid lipofuscinosis disorders
CLN1 - CLN14
V. sialic acid
37
Galactosialidosis diseases
Infantile sialic acid storage
Salla
Sialuria
38
Mucolipidosis diseases
Sialidosis I and II (mucolipidois I)
I-cell (mucolipidois II)*
Psuedo-Hurler-Polydystrophy (mucolipidois III)
Mucolipidois IV
39
Miscellaneous LSD's
Lysosomal acid lipase deficiency (Infant, Child, Adult) (cholesterols, triglycerides)
Pompe (Glycogen type II)
Danon (Glycogen)
Cystinosis (Cystine)
40
What happens when eIF-2 is phosphorylated
Inactivated
41
What is a nuclear signal and where is it located in the protein
Short, basic, and internally
42
What is a mitochondrial signal and where is it located
N-terminal, amphipathic, alpha-helix entry sequence
43
What is a peroxisomal signal and where is it located
C-terminus tripeptide signal
44
What amino acids have phosphorylation occur
Serine*
Threonine
Tyrosine
45
What amino acids have glycosylation occur
Asparagine
Arginine
Cysteine
Glutamine
Hydroxylysine
Hydroxyproline
Serine*
Threonine*
Tryptophan
Tyrosine
46
What amino acids have hydroxylation occur
Proline
Lysine
(Vitamin C dependent hydroxylases)
47
Where does N-glycosylation occur
Rough ER
48
Where does O-glycosylation occur
Golgi
49
What molecule signals transport of N-glycosylated acid hydrolases for lysosomes
Mannose-6-phosphate
50
What amino acid have carboxylation occur
Glutamate (Vitamin K dependent carboxylases)
51
What amino acids are biotinylated
Epsilon-amino groups of lysine
52
What amino acid is farnesylated
Cysteine
53
What is a peroxisomal importomer
Tripeptide sequence on C-terminus indicating peroxisome destination
54
What is the cause of Zellweger syndrome
Peroxisome formation defects
55
What is the cellular stress response
UPR (Unfolded Protein Response)
56
What is the UPR pathway
Stress
PERK represses mRNA by phosphorylating eIF-2
P-IRE1 recruits tumor necrosis factor (TNF) receptor associated factor 2 (TRAF2) to activate kinases
Activated JNK phosphorylates activator protein 1 (AP1)
Activated IKK phosphorylates IB
Activated NF-B and AP1 enter nucleus inducing inflammatory genes
57
Diseases related to UPR overreaction
Creutzfeldt-Jakob
Alzheimer
Parkinson
Huntington
Atherosclerosis
Obesity
Diabetes type II
Neurodegenerative diseases
58
Movement from ER to Golgi is mediated by
COP II
59
Movement from Golgi back to ER is mediated by
COP I
60
What is the retrieval signal between ER and Golgi
KDEL
61
What is the final glycan released by the Golgi
4 GlcNAc
3 Mannose
2 Galactose
2 Sialic acid
62
What surrounds M6P containing vessicles
Clathrin
63
Golgi functions
Synthesis and loading of lysosomes
Recycle plasma membrane
Modify glycoproteins and hormones from RER
O-linked glycosylation
Modified phosphorylation
64
Lysosome funcitons
Degrade cellular debris
Maintain macromolecules
65
What are multivesicular bodies
endosomal compartments that sort ubiquitinated membrane proteins by incorporating them into vesicles
66
MVB proteins that incorporate vesicles
ECRT I–III. (Vps4p is an AAA‐type ATPase also involved)
67
Classifications of endosomes
Early
Sorting
Late
68
What does SNARE protein mean
Soluble N-ethylmaleimide-sensitive factor Attachment Receptor Protein
69
Example of a SNARE protein
Sec22 - associated with atherosclerosis and Alzheimer disease
70
What is the secretion process called of continuous release vesicles
Constitutive secretion
71
What is the secretion process called of discontinuous release vesicles
Regulated secretion
72
Relationship between autophagy and aging
Decreased removal of aggregated proteins
73
Relationship between autophagy and cancer
Attacks tumor cell growth in early stages
Defends in later stages
74
Relationship between autophagy and diabetes and obesity
Decrease in adiposity
Insulin resistance
75
Relationship between autophagy and neurodegeneration
Decreased removal of neuronal aggregated proteins
76
Relationship between autophagy and lysosomal storage disorders
Decreased removal of stored cholesterol and fatty acids
77
Relationship between autophagy and infectious diseases and immunity
Removal of pathogens through sequestration in autophagic vacuoles
78
Standalone features of I-Cell disease
Coarse facial features
Corneal clouding*
Claw hand
79
Standalone features of Gaucher disease
Most common
Avascular necrosis of femur
Thrombocytopenia
Osteoporosis
80
Diseases most common in Ashkenazi Jews
Gaucher (Type I)
Tay-Sachs
Neimann-Pick
81
Key diagnostic feature of Gaucher disease
Gaucher cell - lipid rich macrophages that resemble crumpled tissue paper
82
Standalone features of Fabry disease
Mainly affects boys
Acroparesthesia (Fabry pain)
Angiokeratoma
Anhidrosis/hypohidrosis
83
What other ethnicities commonly have Tay-Sachs
Irish American
French Canadian
Louisiana Cajun
84
Key diagnostic feature of Fabry disease
Foamy urine
Zebra bodies
85
Standalone features of Tay-Sachs
Rapid reduction of physical and mental abilities between 3-6 months
Cherry red spot in macula
No hepatosplenomegaly
86
Key diagnostic feature of Tay-Sachs
Onion lysosomes
87
Standalone features of Krabbe disease
Opisthotonus posture (Tetanus)
Optic atrophy
88
Key diagnostic features of Krabbe
Globoid cell - large multinucleated cell clustered in the brain
89
Standalone features of Niemann-Pick disease
Cherry red spot in macula
Hepatosplenomegaly
90
Key diagnostic features of Niemann-Pick disease
Lipid laden macrophages (foam cells) in marrow, liver, spleen
Cherry red spot in macula
Hepatosplenomegaly
91
Standalone features of metachromatic leukodystrophy (MLD)
Motor regression
Infant or juvenile onset
Ataxia
Hyporeflexia
Progressive demyelination of PNS AND CNS
92
What accumulates in metachromatic leukodystrophy (MLD)
Cerebroside sulfate
93
Key diagnostic features of I-Cell
Inclusion bodies in peripheral lymphocytes
94
Standalone features of Hurler syndrome
Facial dysmorphism
Corneal clouding
Inguinal hernias
95
Key diagnostic features of Hurler syndrome
Test urine for GAG's
Test blood for alpha-L-iduronidase
96
Standalone features of Hunter syndrome
Facial dysmorphism (mild)
Aggressive behavior
Carpal tunnel syndrome
97
Key diagnostic features of Hunter syndrome
Test urine for GAG's
Test blood for iduronate-2-sulfatase
98
Structural components of basal lamina
Type IV collagen
Laminins
Entactin (Nidogen)
Perlecan
99
What is Type IV collagen
3 dimensional network of trimeric a-chain collagen proteins containing rodlike or spherical domains
100
Collagen IV dysfunction diseases
Alport syndrome
Goodpasture syndrome
101
What causes Alport syndrome
Mutations in C-terminal globular domain of certain collagen IV chains
102
Symptoms of Alport syndrome
Progressive renal failure
Sensorineural hearing loss
Ocular abnormalities
103
What is Goodpasture syndrome
a rare autoimmune disease, auto-antibodies bind to the 3 chains of type IV collagen in the glomerular basement membrane and lungs
104
Symptoms of Goodpasture syndrome
Progressive renal failure Pulmonary hemorrhage
105
What are laminins
Glycoproteins with α, β, and γ chains that bind with type IV collagen, proteins, polysaccharides, receptors, growth factors, and hormones
106
Laminin deficiency diseases
Laminin α2-dystrophy (merosin deficiency)
Epidermolysis bullosa
Pierson syndrome
Dilated cardiomyopathy
107
What causes laminin α2-dystrophy
Mutation in LAMA2 gene
108
Symptoms of laminin α2-dystrophy
Hypotonia
Respiratory failure
Contractures
109
What causes epidermolysis bullosa
Mutation in LAMA3
110
What causes Pierson syndrome
Mutation in LAMA2
111
Symptoms of Pierson syndrome
Congenital nephrotic syndrome
Ocular abnormalities
Neurological abnormalities
112
What causes dilated cardiomyopathy
Mutations in laminin A/C genes
113
What is entactin (nidogen)
Rod-like sulfated protein crosslinking laminin and collagen type IV incorporating ECM components
114
Entactin (Nidogen) deficiency syndromes
Oral cavity squamous cell carcinoma
Gastric cancer
Clivus chordoma
115
What causes oral cavity squamous cell carcinoma
Nidogen-1 upregulated
116
What causes gastric cancer
Nidogen-2 is upregulated
117
What causes Clivus chordoma
Mutation in nidogen-2
118
Symptoms of Clivus chordoma
Malignant tumors at primitive notochord
119
What is perlecan
Large proteoglycan multidomain crosslinking and binding ECM and cell surface proteins
120
Perlecan dysfunction diseases
Myotonic myopathy
Schwartz Jampel syndrome
121
What causes myotonic myopathy
Mutation in HSGP2
122
What causes Schwartz Jamel syndrome
Mutation in HSGP2
123
Symptoms of Schwartz Jamel syndrome
Myotonia
Chondrodysplasia
Impaired collagen and bone development
124
Functions of basal lamina
Structural foundation for epithelium
Selectively permeable barrier
Collection site for soluble proteins
Guidance signal for migrating neurons
Embryonic development
Tissue regeneration
125
Components of ECM structure
Adhesive proteins
Structural proteins
Proteoglycans
126
What is the function of adhesive proteins
Anchor and link
127
Examples of adhesive ECM proteins
Integrins
Cadherins
Actin
128
Function of structural ECM proteins
Strength
Mechanical resistance
Firmness
129
Example of structural ECM proteins
Collagen
Elastin
Keratin
130
Function of proteoglycans
Hydrate cells
Cushion cells
131
Examples of proteoglycans
Chondroitin
Keratin sulfate
Hyaluronic acid
132
What synthesizes and secretes ECM
Fibroblasts
133
Fibril forming collagen types
I
II
III
134
Network forming collagen types
IV
VIII
135
Fibril associated collagen types
IX
XII
136
Key structure of collagen
Glycine-proline-hydroxyproline with hydroxylysine
137
What 2 cofactors are required for collagen synthesis
Vitamin C
Iron (Fe2+)
138
What specific enzymes degrade collagen
Matrix metalloproteinase (MMP)
Cathepsin K
Plasmin and proteinases
139
What remodels ECM
Zinc-dependent Matrix Metalloproteinases (MMP's)
A Disintegrin And Metalloproteinase with Thrombospondin (ADAMT)
140
In what environment are plasmin and cathepsin G (serine proteinases) active
Neutral pH
141
In what environment are lysosomal cathepsin B and L (cysteine, aspartate, and threonine proteinases) active
Acidic pH
142
What regulates MMP's and ADAMT's
Tissue Inhibitors of Matrix Metalloproteinases (TIMP's)
143
What happens to vascular smooth muscle when elastin is fragmented
Calcification
144
What is a reversible issue for elastin normally but irreversible with oxidation
Glycation
145
What enzyme dysregulation can affect elastin's durability
MMP's
146
What causes osteogenesis imperfecta (brittle bone or Lobstein syndrome)
Mutation in COL1A1 and COL1A2 causing collagen type I deficiency
147
How many types of Lobstein syndrome are there and what are the genotypes for each
4
Type 1 - autosomal dominant
Type 2 - autosomal both
Type 3 - autosomal both
Type 4 - autosomal dominant
148
Symptoms of Lobstein syndrome
Excessive bone fractures
Bone deformities
Short height
Basilar invagination
149
Types of Ehlers-Danlos syndrome
Type 1
Type 2
Type 3
Type 4
Type 6
Type 7a
Type 7b
Type 7c
150
What is Ehlers-Danlos syndrome
Structural weakness in connective tissue due to defective collagen (joint hypermobility and increased bleeding)
151
Symptoms of scurvy
Perifollicular hyperkeratosis
Perifollicular hemorrhage
Coiled fragile corkscrew hair
Palpable purpura
Gingivitis
Swollen and painful joints
152
Function of tight junctions
Selective permeability
153
Function of adherens junctions and desmosomes
Cement cells together
Resist tearing
154
Function of gap junctions
Intercellular communication
155
Function of hemidesmosomes
Cement layer to underlying structure
156
Main cell to cell adhesion molecule
E-cadherin
157
What determines cellular barrier permeability
Occludins
Claudins
158
What molecule suppression leads to metastasis of many cancers
E-cadherin
159
What cadherins are in desomosomes
Desmoglein 1
Desmoglein 3
160
What are gap junctions
2 connexon hemi-channels composed of 6 connexin monomers each
161
What are gap junctions gated by
Changes in Vm
Calcium
pH
Phosphorylation/dephos
162
________ extend into the extracellular space and attach via _______ to the basal lamina
Integrins
Laminins
163
What is kinesin
Protein transport of vesicles from inner cell to peripheral
164
What is dynein
Protein that transports vesicles from peripheral to the inner cell
165
What is myosin
A motor protein that supports actin
166
What proteins are associated with tight junctions
Claudins
Occludins
167
What proteins are associated with adhering junctions
Vinculin (Intramembrane anchor)
Catenin (Intramembrane anchor)
Cadherins (Ca dependent adhesion proteins linking anchors)
168
What is pemphigus vulgaris
Autoimmune antibodies against desmoglein 1 and 3
169
What proteins are associated with hemidesmisomes
Integrins
Keratin
170
Function of tight junctions
Prevent pericellular transport
171
Function of adhering junctions
Connects cells to each other
172
Function of desmosomes
Linking transcellular intermediate filaments
173
Function of hemidesmosomes
Anchor cells to basal lamina
Maintain integrity of basal lamina
174
What is bullous pemphigoid
Autoantibodies against hemidesmosomes
175
What is laminin
Protein providing fibrous structure to basement membrane
176
What is fibronectin
Protein that binds collagen to laminins
177
Function of collagen type I
Bone
Skin
Tendons
Ligaments
Fascia
Dentin
Cornea
Organs
Scar tissue (late)
178
Function of collagen type II
Cartilage
Vitreous humor
Intervertebral discs
179
Function of collagen type III (reticulin)
Reticular fibers of the skin
Blood vessels
Scar tissue (early)
Fetal through embryogenesis
180
Function of collagen type IV
Basement membrane
Lens
181
Function of collagen type V
Bone
Skin
Fetal
Placenta
182
Disease associated with collagen type I
Osteogenesis imperfecta
Ehlers-Danlos Type I
183
Disease associated with collagen type II
Achondrogenesis
184
Disease associated with collagen type III
Ehlers-Danlos Type IV
185
Disease associated with collagen type IV
Alport
Goodpasture
186
Disease associated with collagen type V
Ehlers-Danlos (classic)
187
Function of vanca alkaloids
Inhibit microtubule polymerization
188
Function of taxanes/taxels
Inhibit microtubule disassembly/Stabilize GDP-bound tubulin
189
Function of colchicine
Inhibit microtubule polymerization (Gout)
