Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMB > CMB Week 1 > Flashcards

CMB Week 1 Flashcards

1
Q

what is the function of the plasma membrane of cells?

A
  • compartment separation - receptor sites and signal transduction -movement in and out of the cell through channels and carriers on the plasma membrane -cell to cell adhesion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The nucleus is composed of …

A

nuclear membrane, chromatin, nucleolus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the nuclear envelope?

A

double membrane of nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the nucleolus?

A

site of rRNA transcription and ribosome subunit assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the purpose of the ribosome?

A

site of protein synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is glycosylation?

A

addition of glycans to proteins, lipids and other organic molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the function of the smooth ER?

A

lipid synthesis, glycogenolysis, detoxification, Calcium metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of the rough endoplasmic reticulum?

A

contains enzymes for protein folding and glycosylation; membrane specialized for ribosome binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is glycogenolysis?

A

breakdown of glycogen to glucose-6-phosphate and smaller glycogen (n-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the function of the golgi apparatus?

A
  • Glycosylation and deglycosylation of proteins and lipids - Assembly of proteoglycans - Phosphorylation and sulfation of proteoglycans and proteins - Transport of proteins and lipids from RER to lysosomes, secretory granules or plasma membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is an endosome?

A

membrane bound compartment in eukaryotic cells, provides an environment for materials to be sorted before it reaches the degradative lysosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the function of lysosomes?

A

cellular organelles that contain acid hydrolase enzymes that break down waste materials and cellular debris

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the function of peroxisomes?

A

contains the enzyme catalase, which metabolizes hydrogen peroxide. Also contains enzymes for beta oxidation of long chain fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the primary function of the mitochondria?

A

production of ATP and cellular metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the function of microtubules?

A

part of the cytoskeleton, functions - mechanical support, organization of the cytoplasm, transport, motility and chromosome segregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are microfilaments (actin filaments)?

A

thinnest filaments of the cytoskeleton, involved in cytokinesis, movement and changes in cell shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the cytoskeleton?

A

a meshwork of protein filaments within the cytoplasm that is responsible for cell morphology and movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the composition of microtubules?

A

Alpha and beta tubulins form a protofilament. 13 protofilaments align side by side in a circle to form a microtubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are intermediate filaments?

A

part of the cytoskeleton, involved in regulating cell shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is desmin?

A

intermediate filament found in muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is vimentin?

A

intermediate filament found in mesenchymal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is neurofilament protein?

A

intermediate filament found in neuronal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is keratins?

A

intermediate filament found in epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is epithelium tissue?

A

lines or covers organ surfaces, regulates the transport of materials, forms glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the four main types of tissue?

A

epithelium, connective, muscle and nerve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How are subtypes of epithelium tissue classified?

A

by the number of cell layers and the shape of the cells forming the epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the functions of connective tissue?

A

forms skeletal structures (bone, cartilage, tendon and ligament) provides conduit for blood vessels and nerves provides attachment and support

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the function of muscle tissue?

A

specializes in contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the three types of muscle tissue?

A

skeletal, cardiac, and smooth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the function of skeletal tissue?

A

attached to the skeleton for voluntary body movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the function of smooth tissue?

A

responsible for autonomic visceral movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the function of cardiac tissue?

A

muscle forming the walls of the heart chambers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the function of nerve tissue?

A

specialized for transmission of electrical signals which regulate brain function, muscle and gland activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are the two major cell types in nerve tissue?

A

neurons and glia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the function of neurons?

A

cells that generate and receive electrical signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the function of glia cells?

A

provides metabolic and structural support to neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is a globin fold motif?

A

protein motif with 8 alpha helices (A-H) in a specific 3D orientation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is hemoglobin (Hb)?

A

a globular, tetrameric protein found primarily in red blood cells and functions to deliver O2 from lungs to peripheral tissues and eliminate CO2 and protons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is myoglobin?

A

globular protein found primarily in muscles that binds oxygen molecules delivered by Hb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is heme?

A

an iron-chelated porphyrin prosthetic group found in hemoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the principle type of heme found in oxygen binding proteins?

A

Heme B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the composition of heme B?

A

protoporphyrin IX (4-linked pyrrole groups) and a ferrous ion Fe2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Which histidine molecule is replaced when O2 binds to the ferrous ion?

A

the distal Histidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is the composition of Hb?

A

two alpha type subunits and two beta type subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are the alpha type subunits that can be found in Hb?

A

5’ - zeta - alpha2 - alpha1 - 3’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What are the beta type subunits that can be found in Hb?

A

5’ - epsilon - gamma G - gamma A - delta - beta - 3’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Which chromosome are the genes for alpha subunits of Hb localized on?

A

chromosome 16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Which chromosome are the genes for beta subunits of Hb localized on?

A

chromosome 11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the two types of Hb found in embryos?

A

Hb Gower-1 and Hb Portland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the chain composition of Hb Gower-1?

A

ζ2ε2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the chain composition of Hb Portland?

A

ζ2γ2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the chain composition of fetal Hb (HbF)?

A

α2γ2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What % of adult Hb is composed of HbF?

A

less than 1%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is the composition of HbA1 (adult Hb)?

A

α2β2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What % of adult Hb is composed of HbA1?

A

98%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is the composition of HbA2 (adult Hb)?

A

α2δ2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What % of adult Hb is composed of HbA2?

A

2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Approximately how long after birth is HbF replaced with HbA?

A

12-18 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the deoxygenated form of Hb and myoglobin called?

A

Tense state (T-state)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What is the oxygenated form of Hb and myoglobin called?

A

Relaxed (R-state)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is the effect of 2,3-biphosphoglycerate (BPG) on Hb?

A

Increase quantities of BPG —> Increased affinity of Hb to BPG —> decreased affinity of Hb to O2 —>Hb releases O2 (right shift in curve)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is the oxygen-binding curve for myoglobin?

A

Hyperbolic (simple dissociation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is the oxygen-binding curve for hemoglobin?

A

sigmoidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is the Bohr effect?

A

Decrease in pH (periphery -tissues) –> decreases Hb affinity for O2 —> Hb releases O2. Shifts the equilibrium to T-state (right shift in curve)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is the mutation for sickle cell anemia?

A

HbS B6 (beta -6): glutamine to valine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what is the mutation for anemia (HbC)?

A

HbC (beta -6): glutamine to lysine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is the mutation for mild anemia (HbE)?

A

HbE (beta 26): glutamine to lysine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What is the mutation for Hb M-Boston (methemoglobin)?

A

beta58 (histidine to tyrosine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What is the mutation for Hb M-Saskatoon (methemoglobin)?

A

beta63 (histidine to tyrosine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What is carbon monoxide poisoning?

A

Hb has very high affinity for CO —> CO binds Hb 200x stronger than O2, displacing the oxygen. Carboxyhemoglobin circulates in blood for an extended time without releasing the CO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is the treatment for CO poisoning?

A

Using 100% oxygen to compete with the CO, reducing carboxyhemoglobin levels rapidly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is collagen?

A

most abundant (fibrillar) protein in the human body, with 20 different types

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Abnormal collagen synthesis or structure causes dysfunction of…

A
  • cardiovascular organs - bone (fragile) - skin - joints (hyper mobility and arthritis) - eyes (dislocation go lens)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What is the amino acid composition of collagen type I?

A

33% glycine, 10-13% proline, 10% hydroxyproline (OH-Pro), and 1% hydroxylysine (OH-Lys)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What are the three enzymes that are required for post translational modification (hydroxylation) of Pro and Lys?

A

Lysyl hydroxylase Prolyl-4-hydroxylase Prolyl-3-hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is Prolyl-4-hydroxylase?

A

hydroxylates the proline in X-Pro-Gly to 4-OH-Pro

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What is Prolyl-3-hydroxylase?

A

hydroxylates the proline in Hyp-Pro-Gly to 3-OH-Pro

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is a polyproline type II helix?

A

Secondary structure of collagen - each strand is a loose, left-handed helix, with three residues per turn

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What is required in post translational modification of collagen?

A

Fe2+, oxygen, alpha-ketoglutarate, and ascorbic acid (Vit C)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

pinocytosis

A

the non-specific ingestion of fluid and small molecules via small vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

phagocytosis

A

ingestions of large particles, cell debris, bacteria via pseudopodia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

receptor mediated endocytosis

A

allows entry to specific molecules via receptors in the plasma membrane and clathrin coated pit/vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

methemoglobinemia

A

Mutations cannot bind O2, since the Fe2+ ion is oxidized to Fe3+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

thallasemia

A

general term for an autosomal recessive disorder where one of the globin genes is not expressed properly, leading to anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What is the advantage of having glycine in collagen?

A

-small structure allows the formation of triplex - the 3 collagen chains are able to be packed tightly together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What helps stabilize the triplex of collagen (besides Gly)?

A
  • Hydrogen bonds between the neighboring chains - Disulfide chain interactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

telopeptides

A
  • N and C terminus segments in collagen triple helical region -site of cross linking
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What are the steps in the biosynthesis of collagen inside the cell?

A
  1. Translation of alpha chains (two alpha-1 and one alpha-2 chains) on the ribosomes of the RER 2. Peptide chains sent to lumen of RER 3. Signal peptidase cleaves the signal peptides from end of preprocollagen –> procollagen 4. Hydroxylation of Pro and Lys 5. Glycosylation on specific hydroxylysines (helps stabilize the triple helix) 6. Intra and inter chain disulfide bond formation 7. Triple helical structure formed inside RER 8. Procollagen goes to the Golgi Apparatus, glycosylation is completed, and procollagen is secreted via exocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

preprocollagen

A

precursor peptide chains of collagen, with signal peptide that directs the chains to the ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What are the steps in the biosynthesis of collagen outside of the cell?

A
  1. Registration peptides are cleaved from both end of the molecule by procollagen peptidase forming tropocollagen 2. multiple tropocollagen molecules self assemble into collagen fibrils, which form into collagen fibers 3. Maturation - intra and inter molecular cross-links of the tropocollagen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

catalyzes the hydrolysis of collagen

A

collagenases - a matrix metalloproteinase (MMPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

after hydrolysis of the collagen by collagenases, this enzyme finishes the degradation

A

gelatinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What are the two major categories of collagen?

A

fibrillar and network-forming

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

Name the fibrillar type collagens

A

types I, II, III, V and XI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Name the network-forming collagen

A

type IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

Name the fibril-associated collagens

A

types IX and XII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What is scurvy?

A

nutritional condition cause by deficiency in vitamin C. very diverse symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

What is Ehler-Danlos Syndrome?

A

group of connective tissue disorders (10 types)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Describe type IV Ehler-Danlos Syndrome

A
  • autosomal dominant mutation resulting in deficiency in type III collagen formation - symptoms: thin skin, easily ruptured arteries and internal viscera
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Describe type VI Ehler-Danlos Syndrome

A
  • autosomal recessive deficiency in lysyl hydroxylase - Symptoms: scoliosis, velvety skin, hypermobile joints, tendency towards ocular injuries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Describe type VII Ehler-Danlos Syndrome

A
  • autosomal dominate mutation leads to an inability to remove the N terminal propeptide - Symptoms: hypermobile joint, prone to joint dislocations, soft skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Describe type IX Ehler-Danlos Syndrome

A
  • X-linked recessive deficiency in lysyl oxidase that results in decreased cross linking - could also be due to copper deficiency - Symptoms: hyper extensible skin, bladder diverticula, skeletal deformities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

What is elastin?

A
  • fibrillar protein that provides elasticity to tissue - fibrous and insoluble in H2O
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Explain secondary structure in elastin

A
  • lacks a secondary structure, has a coiled structure in which the amino acid residues are highly mobile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What is allysines?

A

modified lysine residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

enzyme that catalyze lysine to allysine

A

lysyle amino oxidase also lysyl oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

structure of elastin

A

3 allysines and an unmodified lysine from different regions of the polypeptide chain react to form the heterocyclic structure of desmosine and isodesmosine desmosines covalently cross-link the chains in elastin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

what is needed for protein glycosylation?

A

-an activated sugar (UDP-glucose) - glycosyl transferase enzyme - acceptor protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

In protein glycosylation, how are sugars linked?

A

covalently through O-links: glycans attach to the hydroxyl oxygen (OH) on serine or threonine N-links: glycans are attached to the nitrogen on asparagine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

In N-linked glycosylation, what is the composition of the sugar precursor being added?

A

14 sugar precursor contains 3 glucose, 9 mannose, and 2 N-acetylglucosamine molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

dolichol

A

carrier molecule that is attached to the 14-sugar precursor in N-linked glycosylation, transfers the glycans to the asparagine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What are the two major saccharides from N-linked glycosylation

A
  • high mannose oligos (two N-acetylglucosamines with many mannose residues) - complex oligos: contains any number of of types of saccharides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Inclusion (I)-cell disease

A

a lysosomal storage disease: defective phosphotransferase - enzyme that transfers phosphates to mannose residues on specific proteins, which serves as a marker for these proteins to be moved to the lysosome. Without the marker, the proteins are not transferred to the lysosome, without these proteins, the lysosome cannot degrade substances, leading to a buildup

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

gamma carboxyglutamic acid (Gla)

A
  • glutamate side chain modified with addition of a second carboxyl group - found in clotting factors and other protein of the coagulation cascade - requires vitamin K
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

kinases

A

enzymes that phosphorylate proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

phosphatases

A

enzymes that remove phosphates from proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

in animal cells, which three amino acids are subject to phosphorylation

A

serine, threonine, and tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

which amino acid has sulfate modification

A

tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

proteasome

A

major mechanism for destruction of cellular proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Where is the proteasome located?

A

cytosol and nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

ubiquitin

A

before being recognized by the proteasome, proteins are tagged by ubiquitin, a small 76 amino acid protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

steps of ubiquitin process

A

1) ubiquitin-activating enzyme binds ubiquitin to the enzyme via a high energy (ATP) bond 2) this ubiquitin intermediate is transferred to the substrate protein by ubiquitin-conjugating enzymes 3) the ubiquitin is covalently attached to the amino group of an internal lysine of the protein, carried out by ubiquitin-protein ligases 4) ubiquinated proteins are recognized by the proteasome for degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

disease states associated with the ubiquitin modification system

A
  • defective ubiquitination in cancer result from defective growth promoting proteins - defection ubiquitination is associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What is SUMO-ylation?

A

post-translational modification involved in - transcriptional modification - apoptosis - response to stress - progression through cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

free energy of activation

A

available energy used to form the reaction intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

name the 6 functional classes of enzymes

A
  1. oxidoreductases 2. transferases 3. hydrolases 4. lyases 5. isomerases 6. ligases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

oxidoreductases

A

act on many chemical groupings to add or remove hydrogen atoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

transferases

A

transfer functional groups between donor and acceptor molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

lyases

A

Add water, ammonia or carbon dioxide across double bonds, or remove these elements to produce double bonds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

hydrolases

A

Add water across a bond, hydrolyzing it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

isomerases

A

Carry out many kinds of isomerization (optical or geometric isomers): e.g. L to D isomerizations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

ligases

A

Catalyze reactions in which two chemical groups are joined (or ligated) with the use of energy from ATP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Klenow fragment

A

5’—>3’ exonuclease activity is located on a portion of the enzyme (30kDa) that can be separated from the larger portion of the enzyme (70kDa). The 70kDa fragment contains the 5’—>3’ polymerization and the 3’–>5’ exonuclease activity - this is the Klenow fragment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

(Prokaryotes) Single-stranded DNA-binding proteins (SSB)

A

during replication, binds to the DNA to keep the two strands from annealing (keeps it open)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

(Eukaryotes) Replication protein A (RPA)

A

during replication, binds to the DNA to keep the two strands from annealing (keeps it open)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

Primosome

A

complex consisting of primases, ligases, helicases, and other proteins that bind to the Ori and are necessary to synthesize the primer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

Replisome complex (OriC)

A

contains the primosome and other molecules like SSB, pol III and I that are necessary for DNA replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

replicons

A

In eukaryotic DNA replication, these are the segments between Oris

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

Modification of the primary transcript (precursor to mature RNA) includes:

A
  1. removal of both external and internal nucleotides by ribonucleases 2. base modification 3. addition of nucleotides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

tRNA post-transcriptional modification

A
  • 5’ end of tRNA is removed by ribonuclease P (a ribozyme) - 3’ end is removed, the terminal CCA (cytosine-cytosine-adenine) is synthesized - nucleotide bases are modified
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

mRNA post-transcriptional modification

A
  • addition of a 3’ terminal poly A tail - addition of methylated internal nucleotides and the methylated inverted cap at the 5’ terminus -splicing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

initial velocity (Vo)

A

measured at the very beginning of an enzyme reaction when very little product has been made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

steady state

A

point at which the enzyme-substrate (ES) intermediate remains constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

Assumptions for the Michaelis-Menten rate equations

A
  1. [S] >> [E] so only small amount of S bound to E. 2. [ES] does not change, stays at steady state. 3. Initial velocities (Vo) are used so no P is converted to S.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

Michaelis-Menten equation

A

v = Vmax * [S]/K m + [S]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

What is Km?

A
  • measure of [S] required for effective catalysis to occur - [S] at 1/2 Vmax - estimate of the equilibrium constant for a given enzyme - small Km: tight binding of S to E - large Km: weak binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

What is Vmax?

A
  • theoretical maximal rate of a reaction - at Vmax, all active sites of the enzyme are saturated with substrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

What is kcat?

A
  • turnover number: max number of substrate molecules converted to product per enzyme per unit of time - kcat = Vmax/E * t
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

Competitive enzyme inhibition

A
  • inhibitor binds specifically at the catalytic site, competes with substrate for binding - reversible by substrate - Km increased in presence of competitive inhibitor - more substrate is needed for effective catalysis - Vmax - unchanged
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

Noncompetitive inhibitor

A
  • Binds E or ES complex other than at the catalytic site - substrate can still bind, but with the inhibitor altering the enzyme configuration, the ESI (enzyme-substrate inhibitor) complex becomes inactive - Km - no change, no competition for the substrate binding site - Vmax decreased proportionately to inhibitor concentration (more inhibitors = slower rate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

ACE inhibitors (angiotensin-converting enzyme)

A
  • group of drugs used for treatment of hypertension and congestive heart failure - inhibits ACE to lower blood pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

Methotrexate

A
  • competitively inhibits dihydrofolate reductase (DHFR) - DHFR synthesizes tetrahydrofolate (folic acid), needed for synthesis of DNA, RNA, thymidylates, and proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

Aspirin (as an inhibitor)

A

causes irreversible inactivation of cyclooxygenase (enzyme required for prostaglandin and thromboxane synthesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

Allosteric inhibition

A

allosteric inhibitor binds to the allosteric site —> causes the active site to become distorted —> substrate cannot bind

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Allosteric activation

A

there’s a distorted active site on enzyme (S cannot bind) allosteric activator binds to the allosteric site —> active site changes shape to fit substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

heterotropic effectors

A

Activating and inhibiting effectors that bind at the allosteric sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

homotropic effectors

A

Substrate induces distant allosteric effect when it binds to the catalytic site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

Feedback inhibition

A

Product of a metabolic pathway inhibits the activity of an enzyme involved in its synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

The vast majority of the cells in the body at any given time are in the …

A

Go phase (resting phase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

Cell cycle

A

G1 –> S —> G2 —> Mitosis –> cytokinesis —> Go

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

G1 phase

A

cellular contents (excluding chromosomes) are duplicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

S phase

A

Chromosomes duplicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

G2

A

Cell ‘double checks’ duplicated chromosomes for error, making any needed repairs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

Retinoblastoma protein (pRb)

A
  • tumor suppressor that when hypophosphorylated is ACTIVE: inhibits cell cycle progression - when phosphorylated, pRb is INACTIVE: allowing cell cycle progression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

When it is time for a cell to enter S phase, pRb is..

A

phosphorylated by CDKs (cyclin dependent kinases) and cyclins, which inactivates pRb, allowing cell cycle progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

pRb becomes more and more…

A

phosphorylated as it goes further in the cell cycle and then becomes hypophosphorylated after mitosis (to inhibit a new cycle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

pRb encoded by…

A

Rb1 gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

If both alleles of the Rb1 gene are mutated early in life…

A

the pRb becomes inactivated (allowing cell progression) and results in retinoblastoma - cancer of the eye

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

cyclins

A

regulatory molecules controls a cell’s progress through the cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

CDKs are activated when …

A

bound to a cyclin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

The cyclin-CDK pair …

A

allows phosphorylation to either activate or inactive target proteins for coordinated entry into the next phase of the cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

Cyclins are synthesized…

A

at specific stages of the cell cycle in response to various molecular signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
173
Q

neoplasms

A

abnormal growth of tissue, disturbances in cell cycle control mechanisms are often seen in human neoplasms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
174
Q

Overexpression of cyclin C is associated with what?

A

Overexpression of cyclin C has been found in both neurons and astrocytes in Alzheimer’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
175
Q

….. often expressed abnormally in lung premalignancy and malignancy, negative marker for prognosis

A

Cyclin E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
176
Q

Overexpression of cyclin A

A

accelerates pRb phosphorylation, promoting cell cycle progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
177
Q

p53

A
  • tumor suppressor protein that has a role at G1/S checkpoint. - p53 can activate DNA repair, can induce growth arrest in the presence of damaged DNA, initiates apoptosis if damaged DNA cannot be repaired
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
178
Q

Morphological changes during apoptosis:

A
  • DNA and organelles fragmented and disintegrated - apoptotic body formation that is quickly engulfed by nearby macrophages - no spilling out of content of cell - no inflammation of surrounding area
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
179
Q

cell necrosis

A

traumatic cell death from acute injury with spillage of cell contents into the surrounding area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
180
Q

What are the intracellular signals for apoptosis?

A

Intracellular signals - can be induced to undergo cell death b/c of lack of nutrients, low oxygen, heat, hypercalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
181
Q

The apoptotic pathway can be controlled by:

A

direct transduction from pro-apoptotic cytokines: - Tumor necrosis factor (TNF) - primarily produced by macrophages - Fas Ligand- transmembrane protein that binds to its receptor to induce apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
182
Q

Stem cells have the ability of:

A
  • self-renewal through mitosis (indefinitely) - Differentiating into specialized cell types
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
183
Q

Totipotent stem cells

A

Have the ability to differentiate into all cell types and give rise to an entire organism (e.g. zygote)

184
Q

Progenitor cells

A

cannot divide and reproduce themselves indefinitely

185
Q

Multipotent (progenitor) cells …

A

can give rise to multiple but limited cell lineages e.g. hematopoietic cells can give rise to all blood cell lines but nor cells of the CNS.

186
Q

Unipotent (progenitor) cells

A

can give rise to only one cell or tissue type

187
Q

Embryonic stem cells are derived from

A

Derived from the inner cell mass of the blastocyst prior to implantation

188
Q

Induced pluripotent stem cells

A

Somatic (body) cells which are reprogrammed to be pluripotent

189
Q

Erythrocyte (red blood cell) function

A
  • To deliver oxygen to all cells/tissues of the body through blood circulation - Gas exchange through diffusion through the membrane as cells squeeze through capillaries
190
Q

When RBCs undergo shear stress in constricted vessels, they …

A

release ATP, leading to vessel wall relaxation and dilation thus promoting blood flow

191
Q

RBC structure

A

Plasma membrane of RBC maintains a flexible biconcave disc shape to the cell, which provides greater surface area through gas exchange can occur and increases laminar flow

192
Q

Rouleaux formation

A
  • occurs when level of serum proteins in elevated - RBCS stack or aggregate - nonspecific indicator of the presence of disease
193
Q

Mature human RBCs lacks…

A

a cell nucleus (thus cannot be targeted by viruses) and organelles

194
Q

RBC Development Pathway

A

Hemocytoblast (stem cell) —> proerythroblast (committed cell) —> early erythroblast —> late erythroblast —> normoblast —> reticulocyte —> erythrocyte

195
Q

Hemocytoblast

A
  • stem cell that gives rise to all blood cells - found in the red bone marrow
196
Q

Normoblasts

A

Stage at which immature RBC ejects their organelles

197
Q

Reticulocyte

A
  • no organelles - cell leaves the bone marrow for blood circulation, then most will mature into RBCs - about 1% of red cells in circulation are reticulocytes
198
Q

Maturation from hemocytoblast to mature RBC takes…

A

~7 days

199
Q

How long do RBC’s circulate in the bloodstream?

A

~120 days

200
Q

Factors that lead to hypoxia, thereby stimulating RBC production

A
  • hemorrhage - damage to bone marrow - exposure to high altitude - exercise - hemolytic disease (abnormal breakdown of RBCs) - low Hb levels
201
Q

Where are RBS degraded?

A

Broken down by macrophages within the liver and spleen,(small amount gets broken down in bone marrow).

202
Q

What happens to the plasma membrane of RBCs as they age?

A
  • Phosphatidylserine is a phospholipid normally found only in the inner layer of the RBC membrane - As the membrane ages, it displays phosphatidylserine on its surface, allowing for recognition by macrophages
203
Q

What is the rate of RBC destruction?

A

~2.5 million/second

204
Q

What happens when RBCs are hemolyze in the circulation?

A
  • the RBC fragments are engulfed by macrophages and degraded via lysosomal enzymes and: - Iron is released from the heme molecules and stored or released to the blood - Globin is further broken down to AAs - Heme degrades to bilirubin
205
Q

Hormonal control of RBC concentration

A
  • Erythropoietin is produced and released in response to low blood O2. - Erythropoietin increases RBC production and protects the cell line from apoptosis
206
Q

Heinz bodies

A

small round inclusions found within RBCs that result from: - damaged Hb - an inherited mutation - chronic liver disease The damaged cells will be eliminated by macrophages, often leading to Heinz body anemia

207
Q

Mendel’s 3 Functional Principles

A
  1. Traits are passed on by genes 2. Genes have more than one form called alleles 3. There are at least 2 alleles for each trait
208
Q

Mendel’s 2 laws of inheritance

A
  1. Law of Segregation 2. Law of Independent Assortment
209
Q

Law of Segregation

A

Every individual possesses a pair of alleles for any particular trait and each parent passes only one randomly selected copy of its alleles to offspring

210
Q

Law of Independent Assortment

A

Separate genes code for separate traits, and are passed independently of one another (not entirely correct in modern genetics)

211
Q

genotype

A

genetic makeup of a person

212
Q

phenotype

A

physical appearance

213
Q

Autosomal dominant disorders

A

Manifest in the heterozygous state (one allele is mutated)

214
Q

Incomplete penetrance

A

individual inherits mutant gene, but appears normal

215
Q

variable expressivity

A

A trait is seen in all patients carrying a mutant gene, but is expressed differently in the phenotype

216
Q

Autosomal Recessive disorders

A
  • both alleles at a gene locus is mutated - unaffected parents are called carriers and each of their offspring has 25% of having the autosomal recessive trait - tend to be more severe and appears in childhood
217
Q

X-linked disorders

A
  • occur from mutations on the X chromosome - affected male does not transmit the disease to his son but all of his daughters are carriers
218
Q

X-inactivation

A

One of the X chromosomes is randomly inactivated in the cells of women

219
Q

How many genes on mitochondrial DNA?

A
  • 37 genes, all of which are essential for normal mitochondrial function - 13 of these genes provide instructions for making enzymes involved in oxidative phosphorylation
220
Q

Mitochondrial DNA is usually inherited…

A

from the maternal lineage

221
Q

Mutations in mtDNA mostly affect which system/organs?

A

The central nervous system; organs that are dependent on oxidation phosphorylation

222
Q

Heteroplasmy

A

Presence of more than one mtDNA variant (normal and mutated) within a cell, tissue or individual.

223
Q

DNA sequencing

A

Process of determining the precise order of nucleotides within a DNA molecule

224
Q

Epigenetics

A

The study of changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA

225
Q

Hardy-Weinberg equilibrium equation

A

p (squared) + 2pq + q (squared) = 1; p (Squared) = frequency of homozygosity for allele p q (Squared) = frequency of homozygosity for allele q 2pq = frequency of heterozygosity

226
Q

Imprinting

A

Important functional differences exist b/w the paternal allele and the maternal allele - these differences result from an epigenetic process called imprinting

227
Q

Imprinting occurs in the …

A

ovum or the sperm, before fertilization

228
Q

Maternal imprinting refers to …

A

transcriptional silencing of the maternal allele (Paternal imprint - silence of paternal allele)

229
Q

Prader-Willi syndrome is characterized by

A

mental retardation, short stature, hypotonia, profound hyperphagia, obesity, small hands and feet, and hypogonadism

230
Q

Angelman syndrome is characterized by

A

mental retardation, ataxic gait, seizures, and inappropriate laughter

231
Q

In Prader-Willi syndrome, which chromosome is affected?

A

an interstitial deletion in paternal chromosome 15

232
Q

Heme containing proteins

A
  1. O2 binding proteins - Hb and Myoglobin 2. microsomal and mitochondrial cytochromes 3. enzymes
233
Q

In Angelman syndrome, which chromosome is affected?

A

an interstitial deletion in maternal chromosome 15

234
Q

Enzyme used in the initial enzymatic step in heme biosynthesis

A

ALA-synthase (E1)

235
Q

Enzymes used in the last enzymatic steps in heme biosynthesis

A

E7 - protoporphyrin III oxidase E8 - ferrochelatase

236
Q

ALA-synthase (E1)

A

catalyzes the synthesis of d-Amino-levulinic acid (1st precursor in heme synthesis)

237
Q

The ring system of heme is derived from ….

A

8 residues each of Succinyl CoA and glycine

238
Q

In heme biosynthesis, the Suc-CoA is produced by the …

A

Krebs cycle

239
Q

In heme biosynthesis, the glycine comes from the …

A

cytosol

240
Q

In heme biosynthesis, the Fe2+ ion is transported from the …

A

cytosol

241
Q

Protoporphyrin-III oxidase (E7) ….

A

Converts protoporphyrinogen to protoporphyrin

242
Q

Ferrochelatase (E8) …

A

Inserts the iron (Fe2+) ion into the ring

243
Q

The initial step (E1) and last steps (E7 and E8) of the biosynthesis of heme occur in the

A

mitochondria

244
Q

The intermediate steps in heme take place in the ….

A

cytosol

245
Q

Heme A is found in

A

cytochrome A

246
Q

Heme C is found in

A

cytochrome C

247
Q

ALA synthase is synthesized in the …. and acts in the …..

A

cytosol, mitochondria

248
Q

ALA-synthase uses ….. as a coenzyme for ….

A

pyridoxal-phospate (Vit B6); decarboxylation

249
Q

Two isoforms of ALA synthase

A
  1. ALAS-E or ALAS2 or erythroid - expressed in RBC precursor cells 2. ALAS-N or ALAS 1 - nonspecific isoform
250
Q

Heme acts as a ….inhibitor, repressing …..

A

feedback; transcription of the gene for d-Aminolevulinate synthase

251
Q

Inherited ALAS-E deficiency is responsible for ….

A

sideroblastic anemia

252
Q

Porphyria results in.. .

A

the excretion and accumulation in tissues of heme biosynthetic intermediates

253
Q

Nitrogen oxide is bound to …. of Hb, and is ….

A

bound to the R form of Hb and is released in the periphery when Hb releases O2

254
Q

Heme oxygenase is found in …

A

Reticuloendothelial cells

255
Q

Neurologic porphyria

A
  • example of Acute intermittent porphyria - due to porphobilinogen deaminase deficiency (E3) - Permanent nerve damage and death may result if not treated promptly
256
Q

In the first step of heme degradation, heme is converted to …. by ….

A

biliverdin; heme oxygenase

257
Q

What are the extracellular signals for apoptosis?

A

Extracellular signals - hormones, toxins, cytokines, growth factor withdrawal

258
Q

Pluripotent stem cells

A

Can differentiate into any of the fetal or adult cell type, but cannot give rise to an embryo

259
Q

S nitrosothiols (function)

A

When Hb is deoxygenated, RBCs release S nitrosothiols, which dilates vessels thus directing more blood to areas of oxygen depletion

260
Q

Erythropoietin (function)

A

A hormone that acts on hemocytoblasts to become proerythroblast, thereby becoming committed to the RBC line

261
Q

What role does testosterone play on RBC production?

A

Increases production and effectiveness of erythropoietin

262
Q

What organ produces erythropoietin?

A

kidneys

263
Q

Assumptions of the Hardy-Weinberg Law

A

For a single autosomal locus in a large population, genotype frequencies can be calculated from allele frequencies after one generation if: 1) mating takes place at random 2) allele frequencies are the same in men and women 3) mutation, selection, and migration are negligible

264
Q

Hematocrit

A

Volume percentage of RBCs in blood (normal in adults 40-45%)

265
Q

Mean Corpuscular Volume (MCV)

A
  • average volume of one RBC - Total blood volume * Hematocrit/# of RBCs
266
Q

Mean Corpuscular Hemoglobin (MCH)

A

In a blood sample, the average mass of Hb per red blood cell

267
Q

Allosteric activators …. the apparent Km

A

decrease

268
Q

Allosteric inhibitors … the apparent Km

A

increase

269
Q

In heme degradation, biliverdin is reduced by …. to …. This reaction requires …

A

In heme degradation, biliverdin is reduced by biliverdin reductase to bilirubin IX. This reaction requires NADPH.

270
Q

Where is bilirubin catabolized?

A

Liver

271
Q

Bilirubin is ….. in aqueous solutions at physiological pH, needs a …. in blood

A

poorly soluble; transporter

272
Q

What is the molecule that transports bilirubin in the blood?

A

albumin

273
Q

Secretion of bilirubin diglucuronide

A

Secreted into bile —> intestine —> feces

274
Q

Some bilirubin diglucuronide can be …. from the intestine and transported to the …. for excretion

A

reabsorbed; kidney

275
Q

Unconjugated bilirubin is bound …. to albumin

A

noncovalently

276
Q

Hyperbilirubinemia

A

abnormalities may occur in any one or more of the biosynthesis steps, leading to hyperbilirubinemia, in which there is either an elevation in unconjugated bilirubin or both unconjugated and conjugated bilirubin

277
Q

Three genetic disorders associated with the overproduction of unconjugated bilirubin (unconjugated Hyperbilirubinemia)

A
  • Gilbert’s syndrome (neonatal jaundice) - Crigler-Najjar syndrome type I - Crigler-Najjar syndrome type II
278
Q
  • Gilbert’s syndrome (neonatal jaundice) - Crigler-Najjar syndrome type I - Crigler-Najjar syndrome type II
A

Three genetic disorders associated with the overproduction of unconjugated bilirubin (unconjugated Hyperbilirubinemia)

279
Q

These disorders are caused by a mutation in what gene? Gilbert’s syndrome (neonatal jaundice); Crigler-Najjar syndrome type I and type II

A

glucuronyl transferase gene

280
Q

Crigler-Najjar syndrome type I is associated with …

A

severe jaundice and neurological impairment due to kernicterus (bilirubin encephalopathy)

281
Q

Crigler-Najjar syndrome type II is less …. and is associated with

A

severe; lower serum bilirubin concentration and affected patients survive into adulthood without neurological impairment

282
Q

In neonatal or physiological jaundice, the glucuronyl transferase enzyme is …

A

temporarily decreased in newborns

283
Q

Neonatal or physiological jaundice resolves itself as …; and the infant is treated with …

A

the liver matures after a few days following birth; exposure to UV light

284
Q

Anemia is a condition in which the body does not have enough …

A

healthy RBCs

285
Q

Two main reasons for anemia

A
  1. underproduction of mature RBCs 2. Loss of RBCs
286
Q

Idiopathic aplastic anemia is a condition in which …

A

the bone marrow fails to properly make blood cells. May result from injury to the blood stem cells

287
Q

Aase syndrome

A

anemia caused by poor development of the bone marrow

288
Q

Fanconi’s anemia

A

due to an abnormal gene that damages cells, which keeps them from repairing damaged DNA

289
Q

Megaloblastic anemia

A

anemia with larger then normal RBCs due to deficiency in folic acid or vit B12

290
Q

Pernicious anemia

A

decrease in RBCs that occurs when the body cannot properly absorb B12 from the gastrointestinal tract

291
Q

Hypochromic anemia

A

underproduction of Hb, less Hb is deposited in the cells

292
Q

Iron deficiency anemia

A
  • most common form of anemia - causes of Fe deficiency: blood loss, poor absorption of Fe by the body, and too little Fe in the diet
293
Q

Hemolytic anemia

A

Due to premature destruction of RBCs

294
Q

Intrinsic (genetic) reasons for hemolytic anemia

A
  • abnormalities in the proteins that build normal RBCs - hemoglobinopathies
295
Q

Extrinsic reasons for hemolytic anemia

A
  • abnormal immune system responses - blood clots in small blood vessels - certain infections - side effects from medications
296
Q

Congenital spherocytic anemia

A

disorder of the surface layer (membrane) of RBCs - leads to RBCs that are shaped like spheres and premature breakdown of RBCs

297
Q

…. can modify bases and cause the introduction of base changes to subsequent DNA replication. These inducers of mutations are called ….

A

Chemical and irradiation-inducted reactions; mutagens

298
Q

Phenotypically silent mutations

A

If a mutation occurs in the noncoding regions of the DNA sequence. Will not alter proteins

299
Q

Silent mutation

A

mutations that occur within coding sequence, but does not cause a change in the protein

300
Q

Phenotypically expressed mutations

A
  • If the mutation occurs in coding regions and causes a change in protein, its presence will be known. - Alters the structure and function of the protein - phenotypically expressed mutation may or may not result in pathology
301
Q

Conservative change (amino acid)

A
  • when an amino acid is changed to another AA of similar size and chemical nature - generally does not change the structure of the protein
302
Q

Non-conservative change (amino acid)

A
  • when an AA is changed to another AA of different size and/or chemical nature - usually results in the change of the structure of the protein
303
Q

Invariant Amino Acids

A
  • AAs that are necessary for the function of the protein - if change occurs in the functionally active site of the molecule, even conservative changes can result in the loss of function
304
Q

Missense mutations

A

Point mutations where a base change causes coding for a different AA

305
Q

Nonsense mutations

A

Result when a codon that codes for an AA is mutated to form a termination codon

306
Q

Read-through mutation

A

Mutation of termination codon to an AA codon, resulting in a larger than normal protein

307
Q

Frameshift mutation

A

Caused by the insertion or deletion of a single nucleotide within the coding region

308
Q

Transition mutation

A

when one purine-pyrimidine pair is substituted for another purine-pyrimidine pair

309
Q

Transversion mutation

A

a purine-pyrimidine pair is substituted for a pyrimidine-purine pair

310
Q

Triplet expansion mutation

A
  • generally a series of G and C that are repeated hundreds or thousands of times
311
Q

While both the alpha and beta genes may have mutations, the most frequently seen hemoglobinopathies result from mutations in the ….

A

beta gene

312
Q

Mutations of Hb globin genes can cause …

A
  1. unstable Hb structure 2. increased or decreased O2 affinity 3. increase in the rate of oxidation of the heme Fe2+ ion to the ferric Fe3+ state 4. an imbalance in the synthesis of globin chains 5. changes in the properties of the globin chain
313
Q

Beta-thalassemia

A

synthesis of the beta globin gene is decreased or absent

314
Q

How is HbF affected by beta-thalassemias?

A

HbF is synthesized normally since the alpha chain (and gamma subunit) synthesis is normal

315
Q

In beta-thalassemia, the alpha chains form …., and these …. resulting in cell death, thus RBC cannot …

A

In β-thalassemia, the alpha chains form tetramers, and these precipitate resulting in cell death, thus RBC cannot mature

316
Q

Hb Bart’s

A
  • gamma tetramer - found in individuals with α-thalassemia and β-thalassemia
317
Q

Beta Thalassemia minor

A
  • Individuals make some adult hemoglobin - only one of the beta globin alleles is mutated (heterozygous) - microcytic anemia
318
Q

Genotype for beta thalassemia minor

A

β/β-

319
Q

Beta thalassemia major (Cooley’s disease)

A
  • homozygous - both alleles of beta chain are mutated - severe anemia (hypochromic anemia) - need blood transfusions - short life span (15-25 yrs)
320
Q

Genotype for beta thalassemia major

A

β-/β-

321
Q

α-thalassemia

A

Synthesis of the α-globin chain is defective

322
Q

How many copies of the α-globin gene on each chromosome 16?

A

Two copies (4 alleles)

323
Q

When one of the four α-globin genes is defective, the individual is a …., with …

A

When one of the four α-globin genes is defective, the individual is a silent carrier, with no symptoms

324
Q

Genotype for α-thalassemia (silent carrier)

A

α1/α1 α2/α2-

325
Q

When two of the four α-globin genes are defective, the individual has …., with …

A

When two of the four α-globin genes are defective, the individual has α-thalassemia trait, with mild anemia

326
Q

Genotype for α-thalassemia trait

A

α1-/α1- α2/α2 OR α1/α1- α2/α2-

327
Q

When three of the four α-globin genes are defective, the individual has …., with …

A

When three of the four α-globin genes are defective, the individual has hemoglobin H disease, with mild to severe hemolytic anemia

328
Q

Genotype for Hemoglobin H disease

A

α1-/α1- α2-/α2

329
Q

If all four of the α-globin genes are defective, … results

A

hydrops fetalis (fetal death)

330
Q

Hb Bart’s has an extremely … for oxygen, resulting in almost …. to the tissues

A

Hb Bart’s has an extremely high affinity for oxygen, resulting in almost no oxygen delivery to the tissues

331
Q

In Hemoglobin H disease, … tetramers …

A

beta tetramers precipitate

332
Q

Aneuploidy

A

the presence of an abnormal number of chromosomes in a cell

333
Q

Trisomy

A

the presence of three sets of a chromosome

334
Q

Down’s Syndrome

A
  • trisomy 21 - genetic disorder caused by the presence of all or part of a third copy of chromosome 21. - Associated with physical growth delays, characteristic facial features, and mild to moderate intellectual disability
335
Q

Edward’s syndrome

A
  • trisomy 18 - has a very low rate of survival - heart abnormalities, kidney malformations, and other internal organ disorders
336
Q

Monosomy

A
  • cells are missing a chromosome
337
Q

Trisomy 13

A
  • abnormalities in nervous system, musculoskeletal, and urogenital
338
Q

Trisomy 22

A
  • frequent cause of spontaneous abortion during the first trimester of pregnancy - Progression to the second trimester and livebirth are rare
339
Q

Klinefelter Syndrome

A
  • presence of more then two X chromosomes in males (XXY, XXXY) - primary feature is sterility – more severe if three or more X chromosomes are present
340
Q

Turner Syndrome

A
  • condition in which females are partly or completely missing an X chromosome (XO)
341
Q

Mosaic or Mosaicism

A

denotes the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg

342
Q

Microdeletion

A

tiny deletion that cannot be seen in a chromosome test (karyotype)

343
Q

Barr body

A

inactive X chromosome

344
Q

In females with extra copies of the X chromosome, how many of the X chromosomes is active?

A

Only one X chromosome is active - all extra copies are inactivated

345
Q

Interstitial duplication

A

duplications within a chromosome

346
Q

Interstitial duplication results in … than extra chromosome duplication

A

less impairment

347
Q

When duplicated chromosomes are maternal, it is …

A

more likely to result in pathologies.

348
Q

Chromosome Translocations

A

a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes

349
Q

Balanced Translocation

A

even exchange of material with no extra or missing genetic information

350
Q

Unbalanced Translocation

A

the exchange of chromosome material is unequal resulting in extra or missing genes

351
Q

Karyotype

A

the number and appearance of chromosomes in the nucleus of a eukaryotic cell

352
Q

What type of abnormalities can be seen with karyotype?

A

Monosomy, trisomy, big deletions, duplications and rearrangements

353
Q

Genomic array study

A
  • multiple probes are used - detects small deletions or duplications anywhere in chromosomes
354
Q

Subtelomeric FISH

A

Used to detect small deletions and translocations involving the tips of chromosomes

355
Q

Florescence in-situ hybridization (FISH) can detect …

A

microdeletions and microduplications

356
Q

Pathogenic CNVs are mostly

A
  • bigger - more deletions than duplications - contain genes expressed in CNS
357
Q

Copy Number Variant (CNV)

A
  • structural variations, alterations of the DNA - present in most individuals - due to genetic recombination - most CNVs are stable and heritable
358
Q

Florescence in-situ hybridization (FISH)

A

Use of florescent probes to detect and localize the presence or absence of specific DNA sequences on chromosomes

359
Q

Benign CNVs are mostly

A
  • smaller - present in healthy relative - more duplications than deletions
360
Q

Exome Sequencing

A

a technique for sequencing all the protein-coding genes in a genome

361
Q

Co-dominant Inheritance

A
  • two different versions of the allele can be expressed - each version makes a slightly different protein - Both alleles influence the genetic trait or determine the characteristics of the genetic condition
362
Q

Rett’s Syndrome

A
  • X-linked lethal because males die before birth - neurodevelopmental disease - Only females get disease
363
Q

Heme oxygenase catalyzes the cleavage of the …., opening the ring.

A

Heme oxygenase catalyzes the cleavage of the α-methene bridge on the porphyrin ring, opening the ring.

364
Q

Heme oxygenase requires … to cleave the porphyrin ring.

A

Heme oxygenase requires O2 and NADPH to cleave the porphyrin ring.

365
Q

The α-methene carbon from the porphyrin ring is converted to …, which is released via the ….

A

carbon monoxide (only endogenous source of CO), which is released via the respiratory tract.

366
Q

The iron ion from the breakdown of heme is released in …., bound by…

A

ferric form, ferritin

367
Q

UDP glucuronyl transferase transfers …; forming …

A

UDP glucuronyl transferase transfers UDP glucuronate onto bilirubin IX; forming diglucuronide

368
Q

In normal bile the …. is the major form of excreted bilirubin, with only small amounts of the …

A

In normal bile the diglucuronide is the major form of excreted bilirubin, with only small amounts of the monoglucuronide.

369
Q

Conjugated bilirubin

A

Bilirubin with its glucuronate donor: diglucuronide and monoglucuronide

370
Q

Conjugated bilirubin is relatively …., so very little should circulate in the blood.

A

Conjugated bilirubin is relatively water-soluble, so very little should circulate in the blood.

371
Q

Elevated conjugated bilirubin in circulation leads to high …

A

Elevated conjugated bilirubin in circulation leads to high urinary concentrations with the characteristic deep yellow-brown color

372
Q

The deposition of conjugated and unconjugated bilirubin in skin and the sclera …

A

The deposition of conjugated and unconjugated bilirubin in skin and the sclera gives the yellow to yellow-green color seen in patients with jaundice.

373
Q

Unconjugated bilirubin has a high affinity for …., which leads to the impairment of cell membrane function, especially in the …

A

Unconjugated bilirubin has a high affinity for membrane lipids, which leads to the impairment of cell membrane function, especially in the nervous system.

374
Q

Hepatocellular disease occurs when bilirubin ….

A

Hepatocellular disease occurs when bilirubin binds covalently to serum albumin.

375
Q

What is the rate limiting enzyme in heme biosynthesis?

A

δ-Aminolevulinic Acid Synthase (ALA)

376
Q

What is the most abundant type of collagen in the body?

A

type I (90%)

377
Q

The collagen protein is a … helix, usually composed of … and a third chain with …

A

The collagen protein is a triple helix, usually composed of two identical chains (α1) and a third chain with slightly different chemical composition (α2).

378
Q

The most common pattern (motif) in the amino acid sequence of collagen are …, where X is an …

A

The most common pattern (motif) in the amino acid sequence of collagen are Gly-Pro-X and Gly-X-Hyp, where X is an amino acid other than Gly, Pro, or Hyp

379
Q

Collagen is synthesized by what type of cell?

A

Fibroblast

380
Q

Secondary structure: alpha helix

A
  • right-hand coil or spiral (helix) conformation where each backbone N-H (amide) group is hydrogen bonded to the backbone carboxyl group of an amino acid 4 residues away - the side chains of the amino acid are pointed outward
381
Q

Oxygen trap

A

the storage of blood in the presence of anticoagulant acid citrate dextrose will result in lower levels of BPG, and when this stored blood is transfused, this leads to poor release of O2

382
Q

Genotype for HbS

A

α2βS2

383
Q

Genotype for HbC

A

α2βC2

384
Q

partial pressure of O2 (pO2) in lungs

A

100mm Hg

385
Q

pO2 in tissues

A

26 mm Hg

386
Q

Acidic Bohr effect; location

A

When Hb is deoxygenated, some ionic and hydrogen bonds are formed, and protons are taken up. Occurs in tissues

387
Q

Alkanine Bohr effect; location

A

When Hb is oxygenated, some ionic and hydrogen bonds are broken, and protons are released. Occurs in lungs

388
Q

The amino groups of lysine are enzymatically converted to aldehyde groups to form … This is done by the enzyme …

A

In collagen, the amino groups of lysine are enzymatically converted to aldehyde groups to form allysine. This is done by the enzyme lysyl oxidase.

389
Q

The aldehyde groups on allysine reacts with … or with another … to form covalent bonds, called ….

A

The aldehyde groups on allysine reacts with Lys amino groups or with another aldehyde group of another allysine to form covalent bonds, called cross-links.

390
Q

The enzyme lysyl oxidase is dependent on …

A

copper

391
Q

chain composition of type I collagen

A

two α1 chains and one α 2 chain

392
Q

Defect in intracellular copper transport results in

A

Menke’s kinky hair syndrome

393
Q

Defect in intracellular copper distribution results in

A

cutis laxa (inelastic skin)

394
Q

Elastase

A

enzyme that cleaves and degrade elastin

395
Q

Elastase is inhibited by

A

alpha-1-antitrypsin

396
Q

If elastase inhibitor is decreased in concentration, this causes elastase to …

A

If elastase inhibitor is decreased in concentration, this causes elastase to degrade elastin in the lungs.

397
Q

Two main extracellular fibrillar proteins

A

collagen and elastin

398
Q

Three categories of intracellular fibrillary proteins

A

microfilament, microtubules, and intermediate filament

399
Q

Structure of myosin contains heads that … and a …

A

Structure of myosin contains heads that bind actin and a coiled-coil tail.

400
Q

Microtubules are constructed as …, to enable cells to …

A

Microtubules are constructed as hollow tubes, to enable cells to change shape in response to external and internal signals.

401
Q

Two drugs that interfere with microtubule formation

A

colchicine and taxol

402
Q

Colchicine, … microtubules, resulting in the inhibition of the …

A

Colchicine, disassembles microtubules, resulting in the inhibition of the action of the white blood cells that mediate inflammation by the precipitation of uric acid in the joints.

403
Q

Taxol is used as an … drug because it blocks … by binding to the ….

A

Taxol is used as an anticancer drug because it blocks cell division by binding to the beta-tubulin subunits in the microtubules.

404
Q

Microtubules are formed from the polymerization of

A

a dimer of alpha and beta tubulin (globular proteins)

405
Q

At one end of a protofilament, the alpha subunit is exposed and this is the …

A

At one end of a protofilament, the alpha subunit is exposed and this is the minus end.

406
Q

At one end of a protofilament, the beta subunit is exposed and this is the …

A

At one end of a protofilament, the beta subunit is exposed and this is the plus end.

407
Q

The minus end of the microtubule is called the

A

microtubule organizing center (MOC)

408
Q

The plus end of the microtubule is the …, where …

A

The plus end of the microtubule is the fast-growing end, where tubular monomers are added.

409
Q

The plus ends of the microtubules are oriented toward …

A

The plus ends of the microtubules are oriented toward the cell periphery (outside).

410
Q

Microtubules support the movement of …

A

Microtubules support the movement of organelles and vesicles in the cell.

411
Q

Kinesin is a

A

Kinesin is a motor protein that uses ATP to move along the microtubule.

412
Q

Kinesin has two … that bind to the … and a … that binds the …

A

Kinesin has two heads that bind to the microtubule and a tail that binds the vesicles being transported.

413
Q

Kinesin transports materials to the … of microtubules, i.e. from the … microtubule to the …

A

Kinesin transports materials to the plus end of microtubules, i.e. from the center of the microtubule to the periphery.

414
Q

The movement of kinesin from the minus end of the microtubule to the plus end is called

A

anterograde vesicular traffic

415
Q

Dynein is a

A

motor protein that uses ATP to move along the microtubule.

416
Q

Dyneins move vesicles to the … of the microtubule, i.e. from the …

A

Dyneins move vesicles to the minus end of the microtubule, i.e. from the periphery to the interior of the cell.

417
Q

The movement of dynein from the plus end of the microtubule to the minus end is called

A

retrograde vesicular traffic

418
Q

List the different domains in enzymes:

A
  • prodomain - catalytic domain - substrate-binding site -transmembrane domain
419
Q

Pro domain of the enzyme

A

keeps the enzyme inactive

420
Q

catalytic site of enzymes

A

contains the catalytic residues that catalyze the the reaction by acting on the substrate

421
Q

endogenous inhibitors

A

enzyme inhibitors that are present in the body, and act as naturally occurring inhibitors

422
Q

4 factors that regulate enzyme activity

A

1) substrate availability 2) enzyme availability 3) enzyme activation 4) enzyme inhibitors

423
Q

In enzyme regulation, substrate availability is related to

A
  • amount of substrate available - location of the substrate - conformation of the substrate
424
Q

active site of the enzyme

A

the catalytic site and the substrate-binding site

425
Q

Two types of cyclooxygenase (COX) enzymes

A

COX 1: constitutively expressed, including in the GI mucosa COX 2: induced by inflammation

426
Q

COX inhibitors inhibit …. synthesis. COX inhibitors therefore reduce ….

A

COX inhibitors inhibit prostaglandin and thromboxane synthesis. COX inhibitors therefore reduce inflammation.

427
Q

The valine amino acid on COX 2 allows for …, making COX 2 more …

A

The valine amino acid on COX 2 allows for preferential binding, making COX 2 more selective.

428
Q

Because COX 2 inhibitors are more selective, they have fewer …. than …

A

Because COX 2 inhibitors are more selective, they have fewer GI side effects than general COX inhibitors.

429
Q

Amyloid precursor protein (APP) is a transmembrane protein that is …

A

Amyloid precursor protein (APP) is a transmembrane protein that is critical to neuron growth, survival, and post-injury repair.

430
Q

Normally, APP is cleaved by

A

α-secretase

431
Q

In Alzheimer’s disease, APP is cleaved by …, generating two fragments, …

A

In Alzheimer’s disease, APP is cleaved by β-secretase (BACE1), generating two fragments, APPsβ and C99.

432
Q

In Alzheimer’s disease, the C99 fragment from beta cleavage, is further cleaved by …, generating …

A

In Alzheimer’s disease, the C99 fragment from beta cleavage, is further cleaved by γ-secretase, generating amyloid-beta protein (Aβ).

433
Q

In Alzheimer’s disease, amyloid plagues results from

A

accumulation and deposition of Aβ protein

434
Q

trypsin is secreted by the … as a zymogen, called ….

A

trypsin is secreted by the pancreas as a zymogen, called trypsinogen

435
Q

Trypsinogen is activated in the … by the highly specific enzyme called …

A

Trypsinogen is activated in the bowel by the highly specific enzyme called enterokinase.

436
Q

Acute pancreatitis, as a consequence of …, there is excess of active .. in relation to its …

A

Acute pancreatitis, as a consequence of inflammation/ irritation in the pancreas, there is excess of active trypsin in relation to its inhibitor

437
Q

What are the 4 major classes of proteases?

A
  1. serine proteases 2. aspartyl proteases 3. metalloproteases 4. cysteine proteases
438
Q

Proteases catalyze the …

A

Proteases catalyze the hydrolysis of peptide bonds

439
Q

Metalloproteases Use a metal … to coordinate and activate the …

A

Metalloproteases Use a metal (zinc) to coordinate and activate the attacking water molecule

440
Q

The extracellular matrix (ECM) plays key roles in ….

A

The extracellular matrix (ECM) plays key roles in supporting cells within tissues and maintaining cellular functions, including cell proliferation and differentiation, apoptosis.

441
Q

Matrix metalloproteinases

A

group of enzymes that are capable of degrading all kinds of extracellular matrix proteins

442
Q

Three families of Zn-dependent metalloproteases

A
  1. Matrix metalloproteinases (MMPs) 2. ADAMs (A Disintegrin and Metalloproteinase) 3. ADAMTSs (ADAMs with a thrombospondin motif)
443
Q

Proteases are involved in a wide variety of biological processes such as

A
  • digestion of food - intracellular protein degradation - orchestrating complex biological processes - remodeling of extracellular matrix proteins
444
Q

ADAMTS-2 cleaves

A

the propeptides of type I and II collagen prior to fibril assembly.

445
Q

Ehlers Danlos Syndrome type VIIC is caused by a mutation in …, this leads to…, causing …

A

Ehlers Danlos Syndrome type VIIC is caused by a mutation in ADAMTS-2, this leads to disorganized collagen fibers, causing skin and other connective tissue problems.

446
Q

When developing a catalytic site inhibitor as a drug, it is best to develop a … inhibitor, i.e. the drug will inhibit …. and not …. This reduces the potential …

A

When developing a catalytic site inhibitor as a drug, it is best to develop a selective inhibitor, i.e. the drug will inhibit only the targeted enzyme and not interfere with similar enzymes. This reduces the potential side effects.

447
Q

Protoporphyria: enzyme involved and characteristics

A

Ferrochelatase (E8) levels are down, resulting in the excretion of protoporphyrin IX in the feces. Both liver and erythropoietic tissues are affected

448
Q

General transcription factors

A

minimal requirement for recognition of the promoter, recruitment of RNA polymerase II and initiation of transcription

449
Q

Specific Transcription factors

A
  • bind sequences within and outside of the core promoter - required to regulate gene expression
450
Q

The transcription initiation complex is

A

involved in regulation of transcription; includes RNA polymerases and general transcription factors

451
Q

α2-macroglobulin is an example of an endogenous inhibitor. α2-macroglobulin: function

A

α2-macroglobulin is an example of an endogenous inhibitor. α2-macroglobulin: function - protease inhibitor with a bait region containing cleavage sites for many enzymes. When enzyme cleaves the region, the conformation of α2-macroglobulin tetramer changes and traps the enzyme (inactivates it).

452
Q

Congenital Disorders of Glycosylation (CDG)

A

inborn errors of metabolism in which glycosylation of a variety of tissues of proteins and/or lipids is deficient or defective

453
Q

Post-translational modification of insulin includes

A
  • synthesis of proinsulin in ER (includes folding, oxidation, and signal peptide cleavage) - Transported to Golgi, proinsulin is processed by a series of proteases to form mature insulin
454
Q

… residues in histones can activate transcription.

A

Acetylation of lysine

455
Q

… residues in histones can inactivate transcription

A

Methylation of lysine

CMB (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions