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Module 3 Flashcards

1
Q

I-cell disease affected enzyme (Dr. R)

A

N-Acetylglucosamine-1-phosphotransferase (missing mannose-6-phosphate tag)

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2
Q

I-cell disease biomarker (Dr. R)

A

Elevated lysosomal enzymes in plasma (inclusion bodies)

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3
Q

I-cell disease symptoms (Dr. R)

A

Coarse facial features
Developmental delay
Skeletal abnormalities
Restricted joint movement
Enlarged liver and spleen

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4
Q

Gaucher disease affected enzyme (Dr. R)

A

Glucocerebrosidase

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5
Q

Gaucher disease biomarker (Dr. R)

A

Elevated chitotriosidase

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6
Q

Gaucher disease symptoms (Dr. R)

A

Enlarged liver and spleen
Bone pain
Fatigue
Bruising and bleeding
Lung disease
Growth retardation

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7
Q

Fabry disease affected enzyme (Dr. R)

A

Alpha-galactosidase A

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8
Q

Fabry disease biomarker (Dr. R)

A

Elevated globotriaosylceramide (ceramide trihexoside)

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9
Q

Fabry disease symptoms (Dr. R)

A

Pain in hands and feet
Kidney problems
Heart issues
Angiokeratomas
Corneal opacities
Gastrointestinal problems

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10
Q

Tay-Sachs disease affected enzyme (Dr. R)

A

Hexosaminidase A

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11
Q

Tay-Sachs disease biomarker (Dr. R)

A

Elevated GM2 ganglioside

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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

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13
Q

Krabbe disease affected enzyme (Dr. R)

A

Galactocerebrosidase

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14
Q

Krabbe disease biomarker (Dr. R)

A

Galactocerebroside, psychosine

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15
Q

Krabbe disease symptoms (Dr. R)

A

Peripheral neuropathy
Destruction of oligodendrocytes
Developmental delay
Optic atrophy
Globoid cells

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16
Q

Niemann-Pick disease affected enzyme (Dr. R)

A

Sphingomyelinase

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17
Q

Niemann-Pick disease biomarker (Dr. R)

A

Elevated sphingomyelin

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18
Q

Niemann-Pick disease symptoms (Dr. R)

A

Enlarged liver and spleen
Neurological decline
Ataxia
Interstitial lung disease
Feeding difficulties
Failure to thrive

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19
Q

MLD affected enzyme (Dr. R)

A

Arylsulfatase A

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20
Q

MLD biomarker (Dr. R)

A

Elevated sulfatides

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21
Q

MLD symptoms (Dr. R)

A

Progressive neurological decline
Motor function loss
Behavioral changes
Seizures
Peripheral neuropathy

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22
Q

Hurler syndrome affected enzymes (Dr. R)

A

Alpha-L-iduronidase

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23
Q

Hurler syndrome biomarker (Dr. R)

A

Elevated dermatan sulfate and heparan sulfate

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24
Q

Hurler syndrome symptoms (Dr. R)

A

Developmental delay
Skeletal abnormalities
Airway obstruction
Corneal clouding
Hepatosplenomegaly

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25
Q

Hunter syndrome affected enzymes (Dr. R)

A

Iduronate-2-sulfatase

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26
Q

Hunter syndrome biomarker (Dr. R)

A

Absence of plasma iduoronate-2-sulfatase
Elevated urinary glycosaminoglycan

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27
Q

Hunter syndrome symptoms (Dr. R)

A

Mild Hurler plus aggressive behavior
Hepatosplenomegaly

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28
Q

What is a sphingolipid

A

A lipid molecule with a long-chain or sphingoid base that may be linked to a fatty acid via an amide bond

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29
Q

What is a mucopolysaccharide

A

A polysaccharide formed by repeated disaccharides

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30
Q

Examples of mucopolysaccharide

A

Glycosaminoglycans (GAG’s) (hyaluronic acid, chondroitin/dermatan/heparin/keratan sulfate)
Proteoglycans (aggrecan, decorin)

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31
Q

Examples of sphingolipids

A

Glycosylceramide

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32
Q

Non autosomal recessive LSD’s

A

Fabry disease
Hunter syndrome

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33
Q

Sphingolipidosis diseases

A

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

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34
Q

Oligosaccharide diseases

A

Alfa mannosidiosis
Schindler disease
Aspartylglusocaminuria
Fucosidosis

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35
Q

Mucopolysaccharidosis syndromes

A

Hurler*
Scheie
Hurler-Scheie
Hunter*
San Filippo (A, B, C, D)
Morquio (A, B)
Maroteaux-Lamy
Sly

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36
Q

Neuronal ceroid lipofuscinosis disorders

A

CLN1 - CLN14
V. sialic acid

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37
Q

Galactosialidosis diseases

A

Infantile sialic acid storage
Salla
Sialuria

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38
Q

Mucolipidosis diseases

A

Sialidosis I and II (mucolipidois I)
I-cell (mucolipidois II)*
Psuedo-Hurler-Polydystrophy (mucolipidois III)
Mucolipidois IV

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39
Q

Miscellaneous LSD’s

A

Lysosomal acid lipase deficiency (Infant, Child, Adult) (cholesterols, triglycerides)
Pompe (Glycogen type II)
Danon (Glycogen)
Cystinosis (Cystine)

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40
Q

What happens when eIF-2 is phosphorylated

A

Inactivated

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41
Q

What is a nuclear signal and where is it located in the protein

A

Short, basic, and internally

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42
Q

What is a mitochondrial signal and where is it located

A

N-terminal, amphipathic, alpha-helix entry sequence

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43
Q

What is a peroxisomal signal and where is it located

A

C-terminus tripeptide signal

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44
Q

What amino acids have phosphorylation occur

A

Serine*
Threonine
Tyrosine

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45
Q

What amino acids have glycosylation occur

A

Asparagine
Arginine
Cysteine
Glutamine
Hydroxylysine
Hydroxyproline
Serine*
Threonine*
Tryptophan
Tyrosine

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46
Q

What amino acids have hydroxylation occur

A

Proline
Lysine
(Vitamin C dependent hydroxylases)

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47
Q

Where does N-glycosylation occur

A

Rough ER

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48
Q

Where does O-glycosylation occur

A

Golgi

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49
Q

What molecule signals transport of N-glycosylated acid hydrolases for lysosomes

A

Mannose-6-phosphate

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50
Q

What amino acid have carboxylation occur

A

Glutamate (Vitamin K dependent carboxylases)

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51
Q

What amino acids are biotinylated

A

Epsilon-amino groups of lysine

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52
Q

What amino acid is farnesylated

A

Cysteine

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53
Q

What is a peroxisomal importomer

A

Tripeptide sequence on C-terminus indicating peroxisome destination

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54
Q

What is the cause of Zellweger syndrome

A

Peroxisome formation defects

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55
Q

What is the cellular stress response

A

UPR (Unfolded Protein Response)

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56
Q

What is the UPR pathway

A

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

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57
Q

Diseases related to UPR overreaction

A

Creutzfeldt-Jakob
Alzheimer
Parkinson
Huntington
Atherosclerosis
Obesity
Diabetes type II
Neurodegenerative diseases

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58
Q

Movement from ER to Golgi is mediated by

A

COP II

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59
Q

Movement from Golgi back to ER is mediated by

A

COP I

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60
Q

What is the retrieval signal between ER and Golgi

A

KDEL

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61
Q

What is the final glycan released by the Golgi

A

4 GlcNAc
3 Mannose
2 Galactose
2 Sialic acid

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62
Q

What surrounds M6P containing vessicles

A

Clathrin

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63
Q

Golgi functions

A

Synthesis and loading of lysosomes
Recycle plasma membrane
Modify glycoproteins and hormones from RER
O-linked glycosylation
Modified phosphorylation

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64
Q

Lysosome funcitons

A

Degrade cellular debris
Maintain macromolecules

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65
Q

What are multivesicular bodies

A

endosomal compartments that sort ubiquitinated membrane proteins by incorporating them into vesicles

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66
Q

MVB proteins that incorporate vesicles

A

ECRT I–III. (Vps4p is an AAA‐type ATPase also involved)

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67
Q

Classifications of endosomes

A

Early
Sorting
Late

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68
Q

What does SNARE protein mean

A

Soluble N-ethylmaleimide-sensitive factor Attachment Receptor Protein

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69
Q

Example of a SNARE protein

A

Sec22 - associated with atherosclerosis and Alzheimer disease

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70
Q

What is the secretion process called of continuous release vesicles

A

Constitutive secretion

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71
Q

What is the secretion process called of discontinuous release vesicles

A

Regulated secretion

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72
Q

Relationship between autophagy and aging

A

Decreased removal of aggregated proteins

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73
Q

Relationship between autophagy and cancer

A

Attacks tumor cell growth in early stages
Defends in later stages

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74
Q

Relationship between autophagy and diabetes and obesity

A

Decrease in adiposity
Insulin resistance

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75
Q

Relationship between autophagy and neurodegeneration

A

Decreased removal of neuronal aggregated proteins

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76
Q

Relationship between autophagy and lysosomal storage disorders

A

Decreased removal of stored cholesterol and fatty acids

77
Q

Relationship between autophagy and infectious diseases and immunity

A

Removal of pathogens through sequestration in autophagic vacuoles

78
Q

Standalone features of I-Cell disease

A

Coarse facial features
Corneal clouding*
Claw hand

79
Q

Standalone features of Gaucher disease

A

Most common
Avascular necrosis of femur
Thrombocytopenia
Osteoporosis

80
Q

Diseases most common in Ashkenazi Jews

A

Gaucher (Type I)
Tay-Sachs
Neimann-Pick

81
Q

Key diagnostic feature of Gaucher disease

A

Gaucher cell - lipid rich macrophages that resemble crumpled tissue paper

82
Q

Standalone features of Fabry disease

A

Mainly affects boys
Acroparesthesia (Fabry pain)
Angiokeratoma
Anhidrosis/hypohidrosis

83
Q

What other ethnicities commonly have Tay-Sachs

A

Irish American
French Canadian
Louisiana Cajun

84
Q

Key diagnostic feature of Fabry disease

A

Foamy urine
Zebra bodies

85
Q

Standalone features of Tay-Sachs

A

Rapid reduction of physical and mental abilities between 3-6 months
Cherry red spot in macula
No hepatosplenomegaly

86
Q

Key diagnostic feature of Tay-Sachs

A

Onion lysosomes

87
Q

Standalone features of Krabbe disease

A

Opisthotonus posture (Tetanus)
Optic atrophy

88
Q

Key diagnostic features of Krabbe

A

Globoid cell - large multinucleated cell clustered in the brain

89
Q

Standalone features of Niemann-Pick disease

A

Cherry red spot in macula
Hepatosplenomegaly

90
Q

Key diagnostic features of Niemann-Pick disease

A

Lipid laden macrophages (foam cells) in marrow, liver, spleen
Cherry red spot in macula
Hepatosplenomegaly

91
Q

Standalone features of metachromatic leukodystrophy (MLD)

A

Motor regression
Infant or juvenile onset
Ataxia
Hyporeflexia
Progressive demyelination of PNS AND CNS

92
Q

What accumulates in metachromatic leukodystrophy (MLD)

A

Cerebroside sulfate

93
Q

Key diagnostic features of I-Cell

A

Inclusion bodies in peripheral lymphocytes

94
Q

Standalone features of Hurler syndrome

A

Facial dysmorphism
Corneal clouding
Inguinal hernias

95
Q

Key diagnostic features of Hurler syndrome

A

Test urine for GAG’s
Test blood for alpha-L-iduronidase

96
Q

Standalone features of Hunter syndrome

A

Facial dysmorphism (mild)
Aggressive behavior
Carpal tunnel syndrome

97
Q

Key diagnostic features of Hunter syndrome

A

Test urine for GAG’s
Test blood for iduronate-2-sulfatase

98
Q

Structural components of basal lamina

A

Type IV collagen
Laminins
Entactin (Nidogen)
Perlecan

99
Q

What is Type IV collagen

A

3 dimensional network of trimeric a-chain collagen proteins containing rodlike or spherical domains

100
Q

Collagen IV dysfunction diseases

A

Alport syndrome
Goodpasture syndrome

101
Q

What causes Alport syndrome

A

Mutations in C-terminal globular domain of certain collagen IV chains

102
Q

Symptoms of Alport syndrome

A

Progressive renal failure
Sensorineural hearing loss
Ocular abnormalities

103
Q

What is Goodpasture syndrome

A

a rare autoimmune disease, auto-antibodies bind to the 3 chains of type IV collagen in the glomerular basement membrane and lungs

104
Q

Symptoms of Goodpasture syndrome

A

Progressive renal failure Pulmonary hemorrhage

105
Q

What are laminins

A

Glycoproteins with α, β, and γ chains that bind with type IV collagen, proteins, polysaccharides, receptors, growth factors, and hormones

106
Q

Laminin deficiency diseases

A

Laminin α2-dystrophy (merosin deficiency)
Epidermolysis bullosa
Pierson syndrome
Dilated cardiomyopathy

107
Q

What causes laminin α2-dystrophy

A

Mutation in LAMA2 gene

108
Q

Symptoms of laminin α2-dystrophy

A

Hypotonia
Respiratory failure
Contractures

109
Q

What causes epidermolysis bullosa

A

Mutation in LAMA3

110
Q

What causes Pierson syndrome

A

Mutation in LAMA2

111
Q

Symptoms of Pierson syndrome

A

Congenital nephrotic syndrome
Ocular abnormalities
Neurological abnormalities

112
Q

What causes dilated cardiomyopathy

A

Mutations in laminin A/C genes

113
Q

What is entactin (nidogen)

A

Rod-like sulfated protein crosslinking laminin and collagen type IV incorporating ECM components

114
Q

Entactin (Nidogen) deficiency syndromes

A

Oral cavity squamous cell carcinoma
Gastric cancer
Clivus chordoma

115
Q

What causes oral cavity squamous cell carcinoma

A

Nidogen-1 upregulated

116
Q

What causes gastric cancer

A

Nidogen-2 is upregulated

117
Q

What causes Clivus chordoma

A

Mutation in nidogen-2

118
Q

Symptoms of Clivus chordoma

A

Malignant tumors at primitive notochord

119
Q

What is perlecan

A

Large proteoglycan multidomain crosslinking and binding ECM and cell surface proteins

120
Q

Perlecan dysfunction diseases

A

Myotonic myopathy
Schwartz Jampel syndrome

121
Q

What causes myotonic myopathy

A

Mutation in HSGP2

122
Q

What causes Schwartz Jamel syndrome

A

Mutation in HSGP2

123
Q

Symptoms of Schwartz Jamel syndrome

A

Myotonia
Chondrodysplasia
Impaired collagen and bone development

124
Q

Functions of basal lamina

A

Structural foundation for epithelium
Selectively permeable barrier
Collection site for soluble proteins
Guidance signal for migrating neurons
Embryonic development
Tissue regeneration

125
Q

Components of ECM structure

A

Adhesive proteins
Structural proteins
Proteoglycans

126
Q

What is the function of adhesive proteins

A

Anchor and link

127
Q

Examples of adhesive ECM proteins

A

Integrins
Cadherins
Actin

128
Q

Function of structural ECM proteins

A

Strength
Mechanical resistance
Firmness

129
Q

Example of structural ECM proteins

A

Collagen
Elastin
Keratin

130
Q

Function of proteoglycans

A

Hydrate cells
Cushion cells

131
Q

Examples of proteoglycans

A

Chondroitin
Keratin sulfate
Hyaluronic acid

132
Q

What synthesizes and secretes ECM

A

Fibroblasts

133
Q

Fibril forming collagen types

134
Q

Network forming collagen types

135
Q

Fibril associated collagen types

136
Q

Key structure of collagen

A

Glycine-proline-hydroxyproline with hydroxylysine

137
Q

What 2 cofactors are required for collagen synthesis

A

Vitamin C
Iron (Fe2+)

138
Q

What specific enzymes degrade collagen

A

Matrix metalloproteinase (MMP)
Cathepsin K
Plasmin and proteinases

139
Q

What remodels ECM

A

Zinc-dependent Matrix Metalloproteinases (MMP’s)
A Disintegrin And Metalloproteinase with Thrombospondin (ADAMT)

140
Q

In what environment are plasmin and cathepsin G (serine proteinases) active

A

Neutral pH

141
Q

In what environment are lysosomal cathepsin B and L (cysteine, aspartate, and threonine proteinases) active

142
Q

What regulates MMP’s and ADAMT’s

A

Tissue Inhibitors of Matrix Metalloproteinases (TIMP’s)

143
Q

What happens to vascular smooth muscle when elastin is fragmented

A

Calcification

144
Q

What is a reversible issue for elastin normally but irreversible with oxidation

145
Q

What enzyme dysregulation can affect elastin’s durability

146
Q

What causes osteogenesis imperfecta (brittle bone or Lobstein syndrome)

A

Mutation in COL1A1 and COL1A2 causing collagen type I deficiency

147
Q

How many types of Lobstein syndrome are there and what are the genotypes for each

A

4
Type 1 - autosomal dominant
Type 2 - autosomal both
Type 3 - autosomal both
Type 4 - autosomal dominant

148
Q

Symptoms of Lobstein syndrome

A

Excessive bone fractures
Bone deformities
Short height
Basilar invagination

149
Q

Types of Ehlers-Danlos syndrome

A

Type 1
Type 2
Type 3
Type 4
Type 6
Type 7a
Type 7b
Type 7c

150
Q

What is Ehlers-Danlos syndrome

A

Structural weakness in connective tissue due to defective collagen (joint hypermobility and increased bleeding)

151
Q

Symptoms of scurvy

A

Perifollicular hyperkeratosis
Perifollicular hemorrhage
Coiled fragile corkscrew hair
Palpable purpura
Gingivitis
Swollen and painful joints

152
Q

Function of tight junctions

A

Selective permeability

153
Q

Function of adherens junctions and desmosomes

A

Cement cells together
Resist tearing

154
Q

Function of gap junctions

A

Intercellular communication

155
Q

Function of hemidesmosomes

A

Cement layer to underlying structure

156
Q

Main cell to cell adhesion molecule

A

E-cadherin

157
Q

What determines cellular barrier permeability

A

Occludins
Claudins

158
Q

What molecule suppression leads to metastasis of many cancers

A

E-cadherin

159
Q

What cadherins are in desomosomes

A

Desmoglein 1
Desmoglein 3

160
Q

What are gap junctions

A

2 connexon hemi-channels composed of 6 connexin monomers each

161
Q

What are gap junctions gated by

A

Changes in Vm
Calcium
pH
Phosphorylation/dephos

162
Q

________ extend into the extracellular space and attach via _______ to the basal lamina

A

Integrins
Laminins

163
Q

What is kinesin

A

Protein transport of vesicles from inner cell to peripheral

164
Q

What is dynein

A

Protein that transports vesicles from peripheral to the inner cell

165
Q

What is myosin

A

A motor protein that supports actin

166
Q

What proteins are associated with tight junctions

A

Claudins
Occludins

167
Q

What proteins are associated with adhering junctions

A

Vinculin (Intramembrane anchor)
Catenin (Intramembrane anchor)
Cadherins (Ca dependent adhesion proteins linking anchors)

168
Q

What is pemphigus vulgaris

A

Autoimmune antibodies against desmoglein 1 and 3

169
Q

What proteins are associated with hemidesmisomes

A

Integrins
Keratin

170
Q

Function of tight junctions

A

Prevent pericellular transport

171
Q

Function of adhering junctions

A

Connects cells to each other

172
Q

Function of desmosomes

A

Linking transcellular intermediate filaments

173
Q

Function of hemidesmosomes

A

Anchor cells to basal lamina
Maintain integrity of basal lamina

174
Q

What is bullous pemphigoid

A

Autoantibodies against hemidesmosomes

175
Q

What is laminin

A

Protein providing fibrous structure to basement membrane

176
Q

What is fibronectin

A

Protein that binds collagen to laminins

177
Q

Function of collagen type I

A

Bone
Skin
Tendons
Ligaments
Fascia
Dentin
Cornea
Organs
Scar tissue (late)

178
Q

Function of collagen type II

A

Cartilage
Vitreous humor
Intervertebral discs

179
Q

Function of collagen type III (reticulin)

A

Reticular fibers of the skin
Blood vessels
Scar tissue (early)
Fetal through embryogenesis

180
Q

Function of collagen type IV

A

Basement membrane
Lens

181
Q

Function of collagen type V

A

Bone
Skin
Fetal
Placenta

182
Q

Disease associated with collagen type I

A

Osteogenesis imperfecta
Ehlers-Danlos Type I

183
Q

Disease associated with collagen type II

A

Achondrogenesis

184
Q

Disease associated with collagen type III

A

Ehlers-Danlos Type IV

185
Q

Disease associated with collagen type IV

A

Alport
Goodpasture

186
Q

Disease associated with collagen type V

A

Ehlers-Danlos (classic)

187
Q

Function of vanca alkaloids

A

Inhibit microtubule polymerization

188
Q

Function of taxanes/taxels

A

Inhibit microtubule disassembly/Stabilize GDP-bound tubulin

189
Q

Function of colchicine

A

Inhibit microtubule polymerization (Gout)

Noorda FOM (18 decks)

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