Final Flashcards

1
Q

What does the sliding clamp need to attach to DNA Polymerase?

A

Clamp loader and ATP

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2
Q

Role of DNA Polymerase Alpha?

A

With primase, it synthesizes RNA-DNA primer

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3
Q

What is the role of DNA polymerase epsilon?

A

Synthesizes leading strand

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4
Q

What is the role of DNA Pol delta?

A

Synthesizes lagging strand and fills in gaps

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5
Q

What is the role of FENI?

A

removes primers

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6
Q

Which strand is elongated by telomerase?

A

parent strand

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7
Q

After telomerase adds GGGTTA sequence, what is created to distinguish DNA ends from broken ones?

A

T loop

3’ end longer and tucks to protect ends

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8
Q

Describe dyskeratosis congenita

A

Patients carry mutant telomerase RNA gene. There are premature shortened telomeres

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9
Q

What neutralizes DNA in its chromatin form?

A

Lysine and Arginine residues in Histones: have a positive charge that neutralizes the DNA negative charge

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10
Q

Describe depurination

A

purines are removed due to spontaneous hydrolysis. 5,000 purines lost per day

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11
Q

Describe deamination

A

NH3 group removed due to hydrolysis
A->H
G->X
C->U

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12
Q

Describe the issue with methylated cytosine

A

Accounts for 1/3 of point mutations associated with inherited diseases
Deamination of methyl-C ->T
There is a special DNA glycosylase that removes the T but sucks at its job

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13
Q

What does direct repair fix and with what enzymes?

A

Pyrimidine dimers

DNA photolyase

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14
Q

What does BER fix and with what enzymes?

A

Depurination, single-base mismatch

Glycosylase, AP endonuclease, phosphodiester, DNA Pol beta, and DNA ligase

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15
Q

What does NER fix and with what enzymes?

A

Chemical adducts that distorts DNA

NER protein complex, DNA pol epsilon, and DNA ligase

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16
Q

What does MER fix and with what enzymes?

A

Mismatched base in daughter strand

MER complex, helicase/endonuclease, DNA Pol delta, DNA ligase

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17
Q

What DNA repair mechanism causes cockayne’s syndrome?

A

Transcription-coupled repair. RNA Pol stalled

Growth retard, skeletal abnormal, sensitive to UV

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18
Q

What can happen to the FMRI gene if there are more that 200 copies of CGG?

A

Susceptible to methylation of cytosine and gene becomes silenced

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19
Q

What is the sequence on the tRNA that binds to amino acids?

A

3’CCA

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20
Q

What catalyzes the activation of amino acids and transfers amino acids to tRNA? and how?

A

Aminoacyl tRNA synthetases
Catalyzes the activation of aa by transferring AMP to COOH end
Transfers aa from aa-AMP to cognate tRNA

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21
Q

What is silent mutation?

A

No change of aa

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22
Q

What is missense mutation

A

Changes aa in protein with no effect

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23
Q

What is nonsense mutation?

A

Stop codon, null mutation

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24
Q

What is frameshift mutation?

A

One or more nucleotide are deleted or inserted into open reading fram

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25
Q

What is are the start and stop codons?

A

Start: AUG
Stop: UAA, UAG, UGA

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26
Q

What is snRNA?

A

Direct splicing of pre-mRNA to form mRNA

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27
Q

What is siRNA?

A

Regulate eukaryotic gene expression by degrading select mRNA

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28
Q

What is miRNA?

A

regulates gene expression by blocking translation of select mRNA

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29
Q

What is a polysome?

A

Many ribosomes on one mRNA

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30
Q

Describe the cytoplasmic pathway

A

For proteins destined for cytosol. Mitochondria, nucleus, and peroxisomes

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31
Q

Describe the secretory pthway

A

For proteins destined for ER, lysosomes, secretion, or membranes

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32
Q

What protein binds to ER-target signal and ribosome during translation? What does it do?

A

SRP - wraps itself around ribosome - mRNA complex, tethering it to ER membrane and halting translation temporarily

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33
Q

Large proteins are at rrisk for aggregation and proteolysis, what can help get the protein to its native form?

A

Chaperons or chaperonins

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34
Q

What is the function of proteolytic cleavage?

A

Converts inactive forms to activated enzymes

Converts nascent precursor proteins to mature ones

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35
Q

What is the Law of Segregation?

A

Sexually reproducing organisms possess genes that occur in pairs and only one member of this pair is transmitted to offspring

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36
Q

What is the Law of Independent Assortment

A

The allele transmitted at one locus has no effect on which allele is transmitted at the other

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37
Q

Describe Class 1 - 6 CFTR enzyme defects

A

CFTF - Cl- channel
Class 1: has gene but not expressing protein
Class 2: so unstable its marked for degradation->proteosome
Class 3: Makes it to membrane but not regulated
Class 4: Does not transport well
Class 5: Protein normal but under produced
Class 6: Accelerated turnover

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38
Q

What causes PKU?

A

PAH enzyme defective and causes Phe to build dup

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39
Q

What is recurrent risk?

A

Probability subsequent children will also have disease

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40
Q

What is occurrence risk?

A

Parents at risk, no children-what are the chances of children getting disease

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41
Q

What is Penetrance?

A

Frequency a gene manifests itself

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42
Q

What is expressivity?

A

It is the range of phenotypes for a genotype

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43
Q

What is locus heterogeneity? Give an example

A

Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
Example-osteogenesis imperfecta - loci at 7 and 17; either mutation = same phenotype

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44
Q

What is probability?

A

The proportion of times that a specific outcome occurs in a series of events between 0 and 1

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45
Q

What is the multiplication rule?

A

The probability of two or more independent events occurring together

Key word = ‘and’

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46
Q

What is the addition rule?

A

The probability of any two or more mutually exclusive events

Key = ‘either’ and ‘or’

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47
Q

Describe gene frequency

A

Specifying the proportions of each allele in a population

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48
Q

Describe genotype frequence

A

Specifying proportions of each genotype in a population

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49
Q

Describe polygenic

A

Traitss in which variation caused by combined effects of multiple genes

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50
Q

Describe multifactorial

A

When environmental factors cause variation in trait

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51
Q

Describe the Threshold Model

A

For diseases that do not follow the bell-curve distribution, there is an underlying liability distribution
For multifactorial diseases that are either present or absent, it is thought that a threshold of liability must be crossed before disease is expressed
i.e. pyloric stenosis-muscular hypertrophy btwn stomach and duodenum. 5x more common in men

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52
Q

What is genetic drift?

A

Random evolutionary process that produces larger changes in gene frequency in smaller populations

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53
Q

What is the founder effect?

A

populations that have started from a small group of individuals that mix with few newcomers, preferring to mate within the population, is a special case of genetic drift

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54
Q

What happens in prophase?

A

Chromosomes condense, spindle microtubules form, nuclear envelop breaks, chromosomes are captured by spindle microtubules

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55
Q

Where do spindle microtubules originate from?

A

Centrioles

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56
Q

What are the three checkpoints in a cell life cycle?

A

G1->S
G2->M
M

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57
Q

What keeps chromatids attached and facilitates spindle attachment?

A

Cohesin

Also facilitates recombination

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58
Q

When does crossing over occur?

A

During prophase I in meiotic cell division. Enzymes cut and then graft ends of homologous chromosomes together.

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59
Q

What is recombination?

A

– If the exchanged segments carry different alleles, genetic
recombination has occurred
• The genes on one homologue are thus combined with an allele from the other homologue, and the combination may be totally new

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60
Q

How are chromatids of the maternal and paternal homologues together so that they align precisely along their entire lengths?

A

Proteins

Synaptonemal coomplex

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61
Q

What is a chiasmata?

A

After crossing over, the binding proteins and enzymes then depart, leaving crosses or chiasmata (singular, chiasma),
where the maternal and paternal chromosomes have exchanged parts

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62
Q

How does meiosis create genetic diversity?

A

Meiosis creates genetic
diversity in two ways:
-Random segregation of homologs during meiosis
-Crossing over

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63
Q

What allows X and Y chromosomes to line up?

A

Small region of homology between X and Y called pseudoautosomal
region allows them to pair.

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64
Q

What is a 4 chromatid structure called?

A

Bivalent

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65
Q

When do sister chromatids separate in meiosis?

A

Anaphase II

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66
Q

What are imprinted genes?

A

Genes that are methylated and down regulated

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67
Q

Until ovulation, female gametes are arrested in what stage of meiosis?

A

diplotene

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68
Q

What is aneuploidy?

A

Cells with abnormal chromosome number

Can occur due to non-disjunction which mostly happens during MI

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69
Q

Edwards syndrome is caused by what aneuploidy ?

A

Trisomy 18

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70
Q

Patau syndrome is caused by what aneuploidy ?

A

Trisomy 13

71
Q

What is the restriction point in the cell cycle?

A

it occurs before G1 and it is when cells become growth factor independent

72
Q

Describe how E2F is activated to allow the cell cycle past G1?

A

Mitogen binds to mitogen receptor
Ras is phosphorylated which activates MAP kinase
Gene regulatory proteins are activated and Myc is expressed. Myc activates G1-Cdk.
G1-Cdk phosphorylates Rb to deactivate it and allow E2F to be released.

*More Rb is deactivated by successive cyclin-Cdk

73
Q

Why is Cdk inactive without cyclin?

A

Without cyclin, Cdk’s active site is blocked by T-loop

Binding of cyclins to Cdks causes partial activation of kinase activity

74
Q

What Cyclin-Cdks allow the cell cycle to get past the restriction point? When does the amount of these cyclin-Cdks drop?

A

Cyclin D-Cdk 4
Cyclin D - Cdk 6
Amount drops drastically after transition into S phase

75
Q

What cyclin-Cdks allow the cell cycle to pass the G1 checkpoint and into S phase? When does the amount of the active proteins drop?

A

Cyclin E - Cdk 2

Drop after cell cycle is in S phase

76
Q

What Cyclin-Cdks need to be available during the S phase for DNA synthesis? When does the amount of this protein drop?

A

Cyclin A - Cdk 2

Drops at the end of S phase

77
Q

What cyclin - Cdks slowly build up during G2 phase that is crucial for Mitosis to occur?

A

Cyclin B - Cdk 1

Cyclin A -Cdk 1

78
Q

What triggers the cell cycle to progress from metaphase into anaphase?

A

The destruction of cyclins by APC/C

  • member of ubiquitin ligase family of enzymes
  • S and M -cyclins major target
79
Q

What activates APC/C?

A

Cdc20 binding to APC/C

80
Q

What fully activates cyclin- Cdk?

A

CAK

81
Q

What are two ways cyclin-Cdk(fully active), can be temporarily deactivated?

A

Phosphorylation of roof site by WEE1

P27 binding to protein ( mostly there to control G1-S and S-Cdks early in the cell cycle)

82
Q

What allows for the reactivation of cyclin-Cdk?

A

Dephosphorylation of the roof site by Cdc25

83
Q

What is the role of p53? How is it activated?

A

When there is DNA damage (chemical or physical such as x-rays), protein kinases are activated and they phosphorylate MDM2 which then releases p53.
p53 stops the cell cycle: increases the transcription of p21, a CKI

84
Q

What does p21 do?

A

Binds and inactivates cyclin-Cdk complex and the cell cycle arrested

85
Q

Describe the intrinsic pathway

A

occurs if there are abnormalities in the DNA. Mitochondrial dependent
Cytochrome C released
Cyt C binds to Apaf1 to create apoptosome
Caspase 9 is activated which goes to activate caspase 3

86
Q

When activated, what aggregates and releases cytochrome C?

A

BH123 or Bax

87
Q

What major protein prevents apoptosis?

A

Bcl-2

88
Q

Describe the extrinsic pathway

A

Occurs if there is a removal of survival factors and TNF
Fas (homotrimer) binds to Fas death receptor
Adaptor protein FADD recruited and binds to intracellular death domain
Caspase 8 or 10 activated and DISC is formed
Later caspase 3 activated

89
Q

Is DNA open or closed when the histone is acetylated?

A

Open

Lysine gets acetylated/deacetylated by HAT and HDAC

90
Q

What RNA Pols create mRNA, rRNA, and tRNA, respectively?

A

II
I
III

91
Q

What TFs and Pol are involved in DNA Transcription in order of function?

A

TFIID, B, F, Pol II, E, and H

92
Q

If there is a defect in TFIIH what disease can occur?

A

Xeroelerma pigmentosum, cockaynes syndrome, trichothiodystrophy

93
Q

What three proteins in vivo help transcription to occur when DNA is packaged?

A

Transcriptional activator
Mediator
Chromatin modifying enzymes

94
Q

What step in translation/elongation requires GTP?

A

New tRNA bound to GTP loaded to A site accompanied by GTP hydrolysis and release of factor from aminoacyl tRNA by EF-Tu
EF-Tu also checks to see if it is a match

95
Q

What drugs attack the 30 ribosome subunit?

A

Streptomycin - interrupts initiation

Tetracyclin - interrupts elongation

96
Q

What drug attacks 60 ribosome subunit?

A

Shiga toxin - elongation

97
Q

How much energy is required for translation initiation to begin?

A

1 GTP provides enough energy for the assembly of the initiation complex

98
Q

What drugs/toxins attack the 50 ribosome subunit?

A

Clindamycin and erythromycin

99
Q

What toxin stops translational elongation by attacking the EF-2?

A

Diphtheria

100
Q

What toxin stops translation in both eukaryotes and prokaryotes?

A

Puromycin, similar to tyrosyl-tRNA

101
Q

What protein in mitochondria and prokaryotes is sensitive to chloramphenicol?

A

Peptidy transferase

102
Q

What signal can be found on proteins destined for the ER?

A

KDEL

103
Q

What signal can be found on proteins destined to the nucleus?

A

KKKRK Lys and Arg rich signal

104
Q

What signal can be found on proteins destined for the plasma membrane?

A

stop trsf n terminal apolar region

105
Q

What signal can be found on proteins destined for the mitochondria?

A

N-term hydrophobic alpha-helix signal which helps to interact with chaperone proteins

106
Q

What binds to ER-target signal and ribosome during translation and it wraps itself around ribosome-mRNA-peptide complex tethering it to the ER membrane and halting translation temporarily?

A

SRP

107
Q

What are chaperonins?

A

Barrel shaped compartments that admit unfolded proteins and catalyze their folding in ATP-dependent manner

108
Q

In glycosylation, N-linked is always with what?

A

Amino group of Asn acid amide side chain

109
Q

In glycosylation, O-linked is formed with what groups?

A

O-links are formed with the hydroxyl groups of Ser orThr residues.

110
Q

Describe process of mannose-rich type of glycosylation

A

The core oligosaccharide residue is synthesized on a phosphorylated form of dolichol, an embedded ER membrane isoprenoid.
The 14-residue-core oligosaccharide is transferred as a unit onto Asn
residues. Catalyzed by protein glycosyltransferase
Core structure then trimmed by ER O-glycosidases into the mannose-rich type of glycosylation

111
Q

What inhibits initial sttep of forming core attached to dolichol in glycosylation?

A

Tunicamycin

112
Q

Describe the type of inheritance of 1. Tyr-neg albinism, 2. DMD,
3. Polydactyly and 4. Hypophosphatemia

A
  1. Autosomal recessive
  2. X-linked recessive
  3. Autosomal dominant
  4. X-linked dominant
113
Q

What is the allele on X chromosome called in males?

A

hemizygous

114
Q

Describe hypophosphatemia

A
Low levels of phosphorus in blood
Defective reabsorption in kidneys
Low Ca reabsorption-rickets
Vit D metabolism abnormal
Short limbs
115
Q

Describe what happens at each checkpoint in the cell cycle

A

G1-Correct any DNA damage (chemical modification)
G2-Verify completeness of complete genomic duplication
M-Ensures chromosomes are attached to spindle

116
Q

Translocation between what two chromosomes cause a Philadelphia chromosome to form? what major proteins are involved in this defect?

A

9 and 22

Bcl-2 and ABL

117
Q

What tumor suppressor genes are found on chromosome 17?

A

BRCA1/2 and p53

118
Q

What tumor suppressor genes are found on Chr. 13?

A

Rb

119
Q

What tumor suppressor cell is found on Chr. 5 and is involved in colon cancer?

A

APC

120
Q

What oncogenes are involved in breast cancer?

A

HER2->NEU

121
Q

What oncogene is involved in the translocation of chr. 8 and 14?

A

C-MYC

122
Q

Mutation in beta-catenin causes what?

A

over expression and cell proliferation

123
Q

What Ig is required for sperm to fuse with egg?

A

Izumo

124
Q

How does chimerism occur?

A

Two fraternal twins fuse to form single individual

125
Q

What type of twin is joined at the abdomen and the pelvis, sharing a kidney, liver, bladder and large intestines?

A

Ishiopagus/omphalopagus

126
Q

What type of twin has 2 heads, 1 body, 2 legs, and 2-4 arms?

A

Dicephalus tribrachius

127
Q

What causes crainofacial duplication? (diprosopus)

A

It is not due to abnormal twinning, but rather a protein abnormality in the Shh that leads to facial features duplicated

128
Q

In order for the embryo to “stick” to endometrial lining, what has to be expressed?

A

Both trophoblastic cells and endometrial cells express integrins

129
Q

By week 9, what features of the zygote have developed?

A

Heart, upper limbs, lower limbs

130
Q

What two features of a zygote finish developing at week 9 and 16?

A

Palate

Ear

131
Q

What features are not finished developing until birth?

A

CNS
Eyes
Teeth
External genitalia

132
Q

What cell layer is derived from the epiblast and yolk sac and will act as the supporting layer and continue to separate embryo from surrounding uterine tissue?

A

Extraembryonic mesoderm

Between the inner lining of cytotrophoblast and yolk sac
**Important in forming the materno-fetal interface

133
Q

Define somatic

A

wall of the body cavity (skeletal muscle)

134
Q

Define splanchnic

A

visceral, “internal organs”

135
Q

What is CVS?

A

A type of prenatal diagnostic test to detect chromosomal problems that can result in genetic diseases and birth defects

136
Q

At week 3, what new embryonic feature has formed?

A

Chorion

137
Q

What marks the beginning of gastrulation?

A

Primitive streak - the future axis of the embryo

Narrow line of cells appears on surface of embryonic disk

138
Q

How does the primitive streak elongate?

A

From proliferation of epiblast cells
Cells migrate to center of embryo
And cells are added to caudal end

139
Q

Where is the sacrococcygeal teratoma thought to arise from?

A

The tumor is thought to arises from embryologically multipotent cells from the Hensen node (anterior portion of the primitive streak)

140
Q

What causes caudal dysplasia/caudal regression syndrome or sacral agenesis?

A

Abnormal gastrulation; the migration of mesoderm is disturbed
VATERAL

141
Q

Describe the cascade of the adenylyl cyclase pathway

A

AC Turns ATP in cAMP
cAMP activates PKA by binding to 2 regulatory subunits
PKA phosphorylates

142
Q

What is desensitization?

A

The ability to turn off or reject signal

143
Q

TURN UP TURN DOWN….

A

Potentiate

Attenuate

144
Q

What are 5 ways GPRCs can be desensitized?

A
  1. remove the signaling molecule: phosphodiesterase removes cAMP
  2. Hormone levels drop
  3. Receptor sequestration: endosome
  4. Receptor destruction: endosoome + lysosomes
  5. GRKs-they phosphorylate the receptor so that arrestin can bind to it and prevent Ga from interacting
145
Q

Describe the PLC pathway

A

Gq activates PLC,
PIP2 cleaved to form DAG(membrane bound) and IP3 (diffusible)
IP3 releases Ca from ER/SR
DAG + Ca + PKC(inactive) ->PKC active

146
Q

What is the first oncogene discovered? What is the first human oncogene discovered?

A

Src

Ras

147
Q

Describe insulin signaling - Ras-dependent vs Ras-independent.

A

There is an intermediate scaffold called IRS-1 which binds either Grb2 or PI3K
Grb2 is a Ras dependent pathway that is used if alterations in gene transcription needs to be made
PI3K is independent that is used to alter protein and enzymatic activity through PKb

148
Q

What are eicosanoids?

A

Family of lipid mediators derived from oxidative transformation of 20-C PUFA and they include: prostaglandins, thromboxane, and leukotrienes

149
Q

Why cant autocoids be injected?

A

Because of the pulmonary metabolism by 15-OH-PH DH inactivates PGs, thereby limiting systemic exposure to PGs.

150
Q

How are PGH2 made in general?

A

Cell membrane contains PUFA in their phospholipids and keeps it protected
Stimuli liberates PUFA (most dominant is arachidonic acid) which is the substrate for COX
COX transforms ‘free’ AA into PGH2

151
Q

What are the 5 autocoid mediators that can be made?

A

PGF2, PGD2, PGE2, PGI2 (prostacyclin) and TxA2(thromboxane)

152
Q

Biosynthesis of PGs and Tx are limited to what?

A

Duration and scope by availability of Oxygen and AA and by rapid metabolic degradation

153
Q

Eicosanoid Paracrine cells lack what?

A

enzymes but do have receptors and can respond to eicosanoids

154
Q

What eicosanoid causes vasodilation and decrease in platelet aggregation?

A

PGI2 - released by endothelial cells

155
Q

What eicosanoid causes vasoconstriction and platelet aggregation?

A

TxA2 - Released by platelets

156
Q

What eicosinoid causes permeability of vasculature?

A

PGE2

157
Q

What PG causes mucosal cytoprotection, tone, and motility?

A

PGE2

158
Q

What PG causes NA+, H2O excretion?

A

PGI2 and PGE2

159
Q

What PG causes uterine contractions?

A

PGE2, and PGF2a

160
Q

What PG causes temperature change and pain sensation?

A

PGE2 - CNS

PGE2-PNS

161
Q

What receptors typically relax smooth muscle and cause vasodilation? What pathway is initiated?

A

EP2, EP4, and IP

Gs - cAMP pathway

162
Q

What receptors typically contract and vasoconstrict smooth muscle? What pathway is initiated?

A

FP and TP

Gq: PLC pathway

163
Q

There are physiological antagonist to balance processes. TxA2 and PGI2 are opposing actions. If TxA2 is in excess, what can happen?

A

TxA2 constricts blood vessels and PGI2 relaxes. If there is excess there can be a risk of coronary vasoconstriction = agina pectoris

164
Q

Describe COX-1

A

Constitutive-almost under all conditions, it is there at all times ready to do its job. The system is restrained by locking the PUFA into cell membrane. Use O2 as co-factor and make PGH2

165
Q

Describe COX-2

A

Inducible, not being expressed but becomes available if more PGs are needed. Uses O2 as cofactor and makes PGH2

166
Q

Describe how PGs work in the gastrointestinal system

A
Stimulus is gastric acid
The role of PG is mucosal cytoprotection and gut motility 
The enzyme used is COX-1
PG: PGE2:EP 
Too much causes diarrhea and cramps
Too little-risk of ulcers
167
Q

Describe PG role in the reproductive system

A

Stimulus: endocrine hormones and mechanical stretch
Enzyme: COX-1
PG: PGE2 causes cervical dilation, PGF2a causes uterine contraction
Deficit: Delayed birth
Excess: Pre-mature birth

168
Q

Describe the role of PGs in developmental physiology

A

Stimulus: Fetal lung maturation
Enzyme: Cox-1
PG: PGE2: EP4
Role: maintain patent ductus arteriosus in the fetus. At birht, maturation of neonatal lung ‘withdraws’ PGE2 so that ductus can close

169
Q

Describe the role of PGs in renal physiology

A

Stimulus: renin
Enzymes: Both COX-1 and 2 under all conditions
PG: PGE2
Role: renal blood flow, filtration, and Na, H2O excretion in the kidney
Deficit: Edema, mild hypertension

170
Q

What is the prominent role of COX-2?

A

pathological stimuli - inflammation and cancer.

It amplifies the erythema, edema and pain already created by COX-1

171
Q

What stimulates platelets to release TxA2?

A

Contact to collagen in damaged endothelium

172
Q

What keeps platelet aggregation from spreading?

A

intact endothelium releasing PGI2

173
Q

Why can omega 3 FA possibly reduce the probability of heart attacks?

A

Causes some EPA to replace AA
EPA can be converted to PGH3
PGH3 can form PGI3 which still causes vasodilation
and TxA3 - which has a weaker vasoconstrictor
=anti thrombotic state = less risk of heart attack