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Exam 2 Week 1 Flashcards

1
Q

What 2 different ways can RNA Polymerases begin transcription?

A
  1. Bind the DNA directly at the Promoter (In Prokaryotes)

2. Seek out Transcription Factors that bind the promoter (In Eukaryotes)

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2
Q

What is another name for Constitutive Genes?

A

“Housekeeping Genes” because they are always expressed to ensure basic processes for life

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3
Q

What are the 4 ways expression of a gene can be regulated? Which is most common?

A
  1. Expression Regulation via…
    a. ) Transcription
    b. ) Translation
    c. ) mRNA processing
    d. ) Protein Half-Life
  2. Most Common = TRANSCRIPTION
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4
Q

In Prokaryotes, what is located just upstream of the regulated genes but downstream of the promoter and what is it’s function?

A
  1. Operator

2. Binding site for REGULATORY PROTEINS that alter gene expression (ACTIVATORS/REPRESSORS)

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5
Q

Difference between Activators and Repressors (In Prokaryotes):

A
  1. Activators: Bind TO or NEAR an operator and ALLOW RNA Polymerase to initiate transcription.
  2. Repressors: Bind ONLY TO an operator and PREVENT RNA Polymerase from initiating transcription.
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6
Q

What is the lac operon?

What is just upstream of the lac operon?

A
  1. The prokaryotic gene sequence containing the 3 genes for different proteins necessary for lactose metabolism, as well as the common promoter and operator for those genes.
  2. The Lac-L regulatory protein for the lac operon, which is able to activate gene transcription when lactose is present in the cell.
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7
Q

Describe the 6 DNA sequence locations associated with the Lac Operon:

A
  1. Lac-I: REPRESSOR Protein (when no lactose)
  2. Lac-P: Promoter
  3. Lac-O: Operator
  4. Lac-Z: B-Galactosidase
  5. Lac-Y: Permease
  6. Lac-A: Transacetylase
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8
Q

Describe the functions of Lac Z, Y, and A:

A
  1. Lac-Z: (B-Galactosidase) Converts Lactose into either: a.) Allolactose
    b. ) Glucose + Galactose
  2. Lac-Y: (Permease) Allows active transport of Lactose across the membrane.
  3. Lac-A: (Transacetylase) Converts Galactose into Acetylgalactose.
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9
Q

Where is the Operator located?

A

Upstream of REGULATED GENES

Downstream of PROMOTER

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10
Q

How is Lac-I induced?

A

Allolactose (an isomer of lactose) will bind TO LAC-I, causing a conformational change that will make it dissociate

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11
Q

What is the result of mutations to…

  1. Lac Z-/Y-/A-:
  2. Lac-P-:
  3. Lac-Oc:
  4. Lac-I-:
  5. Lac-Is:
A
  1. Lac Z-/Y-/A-: Non-functional proteins
  2. Lac-P-: Non-functional promoter, so RNA Polymerase can’t bind –> No gene expression
  3. Lac-Oc: Non-functional Operator, so REPRESSOR can’t bind –> (CONSTITUTIVE MUTATION) Genes can’t be shut off and are constitutively expressed.
  4. Lac-I-: Non-functional Repressor: Same as Lac-Oc mutation result.
  5. Lac-Is: Super-Repressor mutation –> Unable to dissociate from operator so system ALWAYS OFF.
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12
Q

Define Negative and Positive Control:

A
  1. Negative Control: Turned off by repressor proteins
    (The Lac Repressor)
  2. Positive Control: Turned on by activator proteins
    (Also exhibited by the Lac Operon)
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13
Q

When would E. Coli exhibit positive control of the Lac Operon? How is this accomplished?

A
  1. When GLUCOSE is LOW –> Activators must induce Lac genes to convert lactose (if present) into glucose
  2. Low Glucose = Increased formation of cAMP from ATP, which binds to the activator proteins CRP (cAMP receptor protein) or CAP (catabolite activator protein) which THEN bind the LacP to induce transcription.
    (i. e. cAMP -> CRP/CAP -> LacP -> Genes Induced)
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14
Q

When might the Lac Operon NOT be induced, EVEN THOUGH Lactose is present?

A

When Glucose is also present, because no cAMP will be produced to stimulate CRP/CAP, which means no Allolactose to remove the Lac-L repressor either.

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15
Q

When might the Lac Operon NOT be induced, EVEN THOUGH Glucose is not present?

A

When Lactose is not present either, because there will be no Allolactose to remove the repressor.

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16
Q

Difference between Cis and Trans Regulatory Elements:

A
  1. Cis: Transcription factor BINDING SITES (enhancer binding sites)
  2. Trans: Transcription Factors/Enhancers
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17
Q

Describe the 3 types of Cis- regulatory elements:

A
  1. Basal Promoter Sequence: Binds Trans Reg Elements in the promoter (that are associated with RNA Pol)
  2. Proximal Regions: Bind Trans Factors NEAR the promoter
  3. Enhancer Sequences: Bind far away from the promoter
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18
Q

Describe the Basal Promoter Region:

A

An A-T Rich region (so it can be opened easily) that contains:
1. TATA Box (-30ish)
2. CAAT Box (-70ish)
And it interacts with the transcription factors that DIRECTLY recruit RNA Pol 2 to the promoter (i.e. It directly interacts with the Basal Transcrip. Apparatus)

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19
Q

If Lac-Z produces Allolactose to remove the Lac-I repressor and allows transcription of the Lac Operon, but Lac-Z ITSELF REQUIRES activation by the Lac Operon, how is this paradox overcome?

A

There is always a SMALL amount of Beta-Galactosidase in the cell to produce the initial Allolactose necessary to remove inhibition of the Lac Operon.

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20
Q

What do each of the three types of Cis-elements provide?

A
  1. Basal Promoter: Low Levels of Expression
  2. Proximal: Increased expression and specificity
  3. Enhancer: Even more increased expression and even more specificity.
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21
Q

How are enhancers able to elicit their effects?

A

Bending/looping of the DNA brings them into close proximity with their target Trans Factors and allows them to UPREGULATE RNA Pol 2 transcription (even if they are UPSTREAM regions or part of an intron!!)

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22
Q

Describe the 3 Domains of Trans Factors:

A
  1. DNA Binding Domains: Regions that only bind DNA at certain sequences.
  2. Dimerization Domains: Regions that bind other Trans Factors to form a dimer, which is then the FUNCTIONAL trans factor capable of DNA-binding. This also adds an element of versatility/complexity.
  3. Activation/Repression Domains: Regions that bind to other trans factors (usually enhancer binding proteins) and modulate their function.
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23
Q

Give 3 examples of Eukaryotic Trans Factors that require dimerization to function:

A
  1. Zinc Fingers
  2. Helix-turn-Helix
  3. Leucine Zipper
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24
Q

How does activator binding influence gene transcription?

A

It STABILIZES the basal transcriptional apparatus (i.e. RNA Pol AND its trans factors) so they may increase the efficiency of transcription INITIATION

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25
Q

Describe the 3 methods by which a Trans Factor can act as a Repressor:

A
  1. Competition: Repressor TF competes with Activator TF for the same enhancer sequence.
  2. Quenching: Repressor TF binds and interferes with the DNA-BINDING DOMAIN of an Activator TF. So there is no activation or repression.
  3. Blocking: Repressor TF binds to the ACTIVATION DOMAIN of an Activator TF and blocks it from interacting with the Basal Transcriptional Apparatus. So no activation or repression.
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26
Q

What is the main difference between Quenching and Blocking:

A

When blocking occurs, the Activator Tf still BINDS to the enhancer sequence but is not functional

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27
Q

What provides “coordinated gene regulation” in eukaryotes that isn’t found in prokaryotes? What 3 things does this allow?

A
  1. The possession of the SAME cis-reg. elements among different genes ON DIFFERENT CHROMOSOMES allows them all to be regulated together by the same Trans Factors (turned off/on at the same time).
  2. This allows:
    a. ) Tissue Specific Expression
    b. ) Stage Specific Expression (during embryonic dev.)
    c. ) Response to External Stimuli
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28
Q

Give 3 examples of external stimuli that may affect regulation of expression via cis-element interaction:

A
  1. Hormones (Hormonal Response Elements)
  2. Hypoxia (Hypoxia Response Elements)
  3. Stress/Heat (Heat Shock Elements)
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29
Q

Define Response Elements:

A

Short sequences of DNA within a gene promoter that bind specific Trans Factors and regulate transcription of their associated gene

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30
Q

What is the Trans Factor that regulates transcription of genes required to respond to Hypoxia? To what does it bind and interact with?

A
  1. HIF-1 (Hypoxia Inducible Factor)

2. HRE’s (Hypoxia Response Elements)

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31
Q

What is required for HIF-1 to interact with HRE’s?

A

HIF-1 Alpha and HIF-1 Beta must dimerize before they can bind the HRE sequence: 5’-TACCTG-3’
Take A Chill (pill), Got to Go… = TACGTG

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32
Q

Differentiate between HIF-1 Alpha and HIF-1 Beta:

A
  1. HIF-1 Alpha: INDUCIBLE and 02-SENSITIVE

2. HIF-1 Beta: CONSTITUTIVE

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33
Q

What happens to HIF-1 Alpha when sufficient oxygen is present?

A

It is hydroxylated and quickly degraded by the proteasome

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34
Q

How does HIF-1 Alpha functions in hypoxic situations?

A

It is stabilized, so it moves to the NUCLEUS where it dimerizes with HIF-1 Beta and elicits its effects

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35
Q

Describe the function of Prolyl Hydroxylase:

A
  1. 02 is the SUBSTRATE which binds it and triggers it to hydroxylate PROLINE RESIDUES.
  2. It does this to HIF-1 Alpha, which tags it for poly-ubiquitination by UBIQUITIN LIGASE.
  3. This tags it for degradation by the proteasome.
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36
Q

What is the key difference between regulation of multiple genes at once in prokaryotes versus eukaryotes?

A
  1. Prokaryotes: Use OPERONS (genes all together)

2. Eukaryotes: Use same Cis-elements (common enhancer sequences) in different, distant genes.

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37
Q

How might HIF-1 be used therapeutically?

A

Cancer survives well in hypoxic environments, so learning how to regulate HIF-1 may lead to selective termination of cancer cells

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38
Q

Describe the Glucocorticoid Receptor (GR):

A
  1. A Zinc-Finger Trans Factor
  2. Up-regulates ANTI-INFLAMMATORY genes (NUCLEUS)
  3. Down-regulates PRO-INFLAMM. genes (CYTOSOL)
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39
Q

Describe the GR Response Element:

A

1, An HRE found in the promoter OR regulatory sequence of many genes.
2. The sequence exhibits INVERTED REPEATS on either side of any nucleotide, “n”:
5’-AGAACAnnnTGTTCT-3’
3’-TCTTGTnnnACAAGA-5’

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40
Q

Where is the GR in the absence of Cortisol (its substrate)? What happens when Cortisol binds it?

A
  1. In the cytosol, inactivated as part of a multi-unit protein complex.
  2. It dissociates from the complex and DIMERIZES with another GR-cortisol monomer before it can translocate into the nucleus and bind HRE’s.
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41
Q

Give another example of a Hormone Response Element mechanism and describe how it works:

A

The Myc/Max system:

  1. In ABSENCE of Myc–> Max forms a homodimer which can ONLY act as a repressor of the enhancer because Max has no trans-activation domain.
  2. In PRESENCE of Myc–> Myc/Max heterodimer forms which acts as an ACTIVATOR of the enhancer sequence.
    i. e. Gene expression ONLY occurs when both MYc and Max are made by the cell!!)
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42
Q

What is the result of Myc over-expression in the cell?

A

Since cMYC regulates 15% of ALL genes, presence of excess Myc will favor heterodimer formation (which promotes PROLIFERATION) instead of homodimer formation of Max (which promotes DIFFERENTIATION), so this can progress into cancer.

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43
Q

What are the 2 Types of RNAi?

A
  1. miRNA: (Micro RNA) Derived from ds-pre-miRNA, they repress mRNA translation
  2. siRNA: (Short Interfering RNA) Derived from long dsRNA’s and “random processing”, they degrade mRNA
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44
Q

What are the 2 Types of Regulation by RNAi? Which type of RNAi is responsible for each?

A
  1. Inhibition of translation on the Ribosome (miRNA)

2. Degradation of the target mRNA (siRNA)

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45
Q

Describe the formation and function of miRNA:

A
  1. Long Primary-miRNA (Pri-miRNA) are processed in the nucleus by DROSHA –> Form Pre-miRNA hairpins.
  2. Pre-miRNA hairpins transported into cytoplasm by EXPORTIN-5.
  3. DICER cleaves the stem loop –> Form ssRNA and dicer initiates formation of RISC (RNA-induced Silencing Complex)
  4. Dicer “feeds” the ss-miRNA to RISC, and the miRNA-RISC complex translocates to its target mRNA, where it binds sequence elements in the 3’-UTR with IMPERFECT BASE PAIRING!! ***
  5. This prevents interaction of the translational machinery with the 5’-cap, so it isn’t translated.
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46
Q

Describe the formation and function of siRNA:

A
  1. Derived from Long dsRNA and “randomly processed” by DICER.
  2. Also complexes with RISC, and translocates to its target mRNA.
  3. siRNA-RISC complex has PERFECT BASE PAIRING with the sequence elements in the 3’-UTR.
  4. This activates the ENDONUCLEASE ACTIVITY of the complex, so the mRNA will be cleaved instead of translated.
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47
Q

How might siRNA be used therapeutically?

A

Recombinant DNA could be synthesized that “forces” a cell to make siRNA that targets specific mRNA for detrimental proteins

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48
Q

How can regulation “DEFINE” a cell?

A

The combination of Transcription Factors and miRNA’s it expresses will determine what type of cell it becomes and what type of activity it exhibits.

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49
Q

What 2 fibrous proteins with a LINEAR STRUCTURE were discussed in lecture?

A
  1. Collagen

2. Elastin

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50
Q

Define Proteoglycans:

A

Negatively charged proteins with a gel-forming sugar

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51
Q

What are the 3 basic components of the Extracellular matrix?

A
  1. Collagen
  2. Elastin
  3. Proteoglycans
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52
Q

What 3 functions does the ECM serve?

A
  1. Maintains the 3D structure of the body
  2. Forms the sheet of the basement membrane
  3. Undergoes constant remodeling by MMP’s (Matrix-Metallo-Proteinases) which include Collagenases
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53
Q

What do MMP’s do and why are they important?

A

They create small holes in the matrix when remodeling the ECM, and these can be exploited by cancer to allow it to propagate and proliferate

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54
Q

Fibrous proteins of the ECM are considered _______.

A

INSOLUBLE

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55
Q

_____ is the most abundant fibrous protein, representing nearly _____% of total body protein mass.

A
  1. Collagen

2. 30%

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56
Q

Structure of Collagen:

A
  1. THREE alpha protein chains form a Triple Helix that is wound tightly to give it a Rope-Like Structure
  2. Every 3rd amino acid in the alpha chains is a GLYCINE, which allows for the tight winding***
  3. Proline and Hydroxyproline residues are abundant and lead to kinks in the chains
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57
Q

Though Proline and Hydroxyproline cause kinks in the Collagen alpha helices, how are they stabilizing?

A

They form many hydrogen bonds between the alpha chains to hold them together

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58
Q

What other residues are involved in the Collagen structure and how?

A
  1. Lysine: Forms COVALENT bonds and CROSS-LINKS TROPOCOLLAGEN
  2. Hydroxylysine: Allows addition of sugars
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59
Q

List the 7 types of Collagen studied in lecture and give their locations: (Also, which are fibril forming, fibril-associated, or network forming?)

A

——–>Fibril Forming:
–>Type 1 = Bone, Blood Vessels, Tendon, Cornea, Skin (BB, Texas Christian Sucks)
–>Type 2 = Intervertebral Disk, Vitreous Body, Cartilage
(IV Cath.)
–>Type 3 = Fetal Skin, Blood Vessels
(Facebook)
——–>Network Forming:
–>Type 4 = Basement Membrane
–>Type 7 = Beneath Strat. Squam. Epithelia
(4+7: Basement Beneath)
——–>Fibril-Associated:
–>Type 9 = Cartilage
–>Type 12 = Tendons/Ligaments
(9+12: Caring Tender Love*)

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60
Q

Describe how collagen is structured differently in 3 different parts of the body:

A
  1. ECM/Vitreous Humor of Eye: Forms a gel
  2. Tendons: Bundle in tight. parallel fibers to provide strength
  3. Bone: Arranged concentrically to resist mech. shear
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61
Q

What do Prolyl Hydroxylase and Lysyl Hydroxylase do?

What do BOTH enzymes require for activity?

A
  1. Prolyl Hydroxylase: Forms Hydroxyproline which adds H-bonds to stabilize the triple helix
  2. Lysyl Hydroxylase: Forms hydroxylysine which has a LONG side chain that is easily GLYCOSYLATED
  3. BOTH require Vitamin C (Ascorbic Acid)
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62
Q

What does Vitamin C Deficiency lead to and how?

A
  1. Scurvy (Bleeding gums, poor wound healing, and hemorrhages)
  2. Deficiency of lysyl hydroxylase activity doesn’t cause instability, but deficiency of prolyl hydroxylase DOES because there are less H-bonds between collagen alpha helices
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63
Q

Describe the concept of collagen synthesis:

A
  1. Synthesis of Procollagen in fibroblasts, chondroblasts, and osteoblasts FROM ONLY 1 OR 2 GENES OUT OF OVER 40 ASSOCIATED GENES.
  2. The 3 pro-chains are modified by hydroxylation and glycosylation and they form a triple helix.
  3. It is released into the ECM, and the chains are cleaved to yield INSOLUBLE collagen molecules that associate to form collagen fibrils.
  4. Covalent Cross-linking by Lysine forms mature collagen
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64
Q

Type 1 Collagen Synthesis:

A
  1. COL1A1/COL1A2 genes allow synthesis of TWO alpha1 chains and ONE alpha2 chain
  2. They associate to form an Alpha1(2)Alpha2 triple helix
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65
Q

How does winding of the triple helix occur?

A
  1. All three pro-alpha chains contain PROPEPTIDES in their C- and N- terminal regions, and are linked COVALENTLY by disulfide bonds at their C-terminus
  2. This allows winding/formation of the tripe helix
  3. Then the N-terminal ends are covalently linked by disulfide bonds to prevent unwinding
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66
Q

Three functions of Pro-Peptides on collagen alpha chains:

A
  1. (In the cytosol) Link the pro-alpha chains at C-terminus
  2. Allow efficient winding of the triple helix
  3. MAINTAIN SOLUBILITY of the formed Procollagen
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67
Q

What happens to Procollagen after it is released into the ECM?

A
  1. Pro-peptides are cleaved by PROCOLLAGEN PEPTIDASES–> Forms TROPOCOLLAGEN
  2. Tropocollagen molecules associate to form a collagen fibril with a staggered arrangement that gives it a STRIATED APPEARANCE
  3. Covalent cross-linking by lysine forms the Mature Collagen FIBERS (not fibril anymore)
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68
Q

How is extracellular covalent cross-linking performed?

A
  1. Lysyl OXIDASE: Requires COPPER to DE-AMINATE lysine residues (IN THE ECM)
  2. This forms FREE NH3 and an Aldehyde Residue known as Allysine (or hydroxy allysine)
  3. It forms covalent bonds with other lysine residues (in both collagen AND elastin synthesis)
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69
Q

List the 2 Collagenopathies discussed in class:

A
  1. Ehlers-Danlos Syndrome

2. Osteogenesis Imperfecta

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70
Q

Describe Ehlers-Danlos Syndrome:

A
  1. A group of hereditary connective tissue disorders
  2. Mutation in the gene for Pro-alpha chains (in either type 1, 3, or 5 collagen)
  3. OR resulting from hereditary defect in an enzyme required for collagen synthesis
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71
Q

Differentiate between the 2 forms of Ehlers-Danlos Syndrome:

A
  1. Classical Form: (Type 5 Collagen deficiency)
    a. ) Hyperextensibility of the Skin
    b. ) Hypermobility of the Joints
  2. Vascular Form: (Type 3 Collagen deficiency)
    a. ) Fragility of the Skin
    b. ) Fragility of Vascular Vessel Walls
    c. ) Lethal Arterial Rupture
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72
Q

Describe Osteogenesis Imperfecta:

Rank the 4 main types from mildest to most severe…

A
  1. “Brittle Bone Disease”: At least 8 TYPES of it
  2. Defective Collagen Synthesis either by:
    a.) Less amounts of normal collagen formed
    b.) More amounts of abnormal Type 1 Collagen, with displaced Glycine = Bone Fractures/Bending
  3. OI Type 1: MILDEST
    OI Type 2: MOST SEVERE
    OI Type 3: In between
    OI Type 4: In between, but normal sclerae
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73
Q

OI Type 1:

A
  1. Osteogenesis Imperfecta TARDA
  2. LONG BONE fractures after trauma in childhood
  3. Less fractures in adulthood when bones aren’t growing
  4. BLUE SCLERAE: Because they are thin and reveal the pigmented uveal tissue underneath
  5. Near normal height, but possibility of hearing loss in adulthood
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74
Q

OI Type 2:

A
  1. Osteogenesis Imperfecta CONGENITA
  2. Death in utero due to neonatal respiratory problems
  3. Underdeveloped lungs and an Abnormal/Small/Fragile Rib Cage
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75
Q

Describe the structure of Elastin:

A
  1. Highly cross-linked
  2. Insoluble
  3. Amorphous
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76
Q

Describe Elastin Synthesis:

A
  1. Fibroblasts secrete Tropoelastin (a highly SOLUBLE, LINEAR polypeptide) into the ECM
  2. Fibrillin-1 acts as a scaffold for Tropoelastin to be cross-linked into INSOLUBLE ELASTIN
  3. Lysyl Oxidase forms Allysine residues in the ECM that perform the cross-linking by forming covalent bonds with other lysine residues on Tropoelastin.
  4. Then 3 Allysine residues and one lysine residue also bond covalently to form a DESMOSINE/ISODESMOSINE (which is characteristic of Elastin) that give elastin its stretching/bending ability
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77
Q

What gives Elastin its stretching ability?

A
  • —->It has alternating domains of:
    1. Hydrophilic Sequences: Rich in Lysine/Alanine (because alanine is not charged and separates the Lysine residues)
    2. Hydrophobic Sequences: Rich in Glycine/Valine/Proline which are non-polar
  • —->This hydrophobic effects allows it to stretch and reform without using energy
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78
Q

What molecules are NOT commonly found in Elastin?

A
  1. Hydroxyproline

2. Hydroxylysine

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79
Q

What does deficiency of Fibrillin-1 lead to and what are the symptoms?

A
  1. Marfan Syndrome (not an Elastin protein mutation, just the scaffolding necessary for its formation)
  2. Characteristics:
    a. ) Long Limbs
    b. ) Arachnodactyly
    c. ) Lens Dislocation
    d. ) Aortic Root Dilation
    e. ) Abnormal Rib Cage Formation
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80
Q

Glycosaminoglycans (GAG’s):

A
  1. Long, Unbranched Chains of (-) Charged Sugars

2. Often SULFATED

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81
Q

Proteoglycans:

A
  1. Contain mainly GAG’s (95%), and some protein

2. Part of the ECM

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82
Q

Glycoproteins:

A
  1. Contain mainly protein, and some carbohydrates

2. The carbohydrates are often BRANCHED

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83
Q

Composition of GAG’s:

A

Position 1: Acidic Sugar (Glucuronic Acid or Iduronic Acid)

Position 2: Amino Sugar (Glucosamine or Galactosamine), which can be acetylated

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84
Q

3 Structural Features of GAG’s:

A
  1. Strong (-) charges from Carboxyl and Sulfate groups
  2. Bind large amounts of water –> Produce a gel-like matrix that is part of the ECM
  3. React in 2 ways:
    a. ) If Compressed: Squeeze water out
    b. ) If Relaxed: Absorb the water
    i. e. Essentially shock absorbers
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85
Q

4 functions of GAG’s:

A
  1. Flexibility supporter of ECM
  2. Molecular Sieve
  3. Lubricant
  4. Shock-Absorber
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86
Q

What are the most abundant GAG’s in the body? Where are they found and where are they sulfated?

A
  1. Chondroitin Sulfates
  2. Sulfated at position 4 or 6
  3. Found in:
    a.) Bone
    b.) Ligaments
    c.) Aorta
    d.) Cartilage
    (BLAC = Most Abundant)
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87
Q

What 3 other types of sulfated GAG’s are there besides Chondroitin Sulfates?

A
  1. Keratin Sulfates
  2. Dermatin Sulfates
  3. Heparin Sulfates
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88
Q

Describe Keratin Sulfates:

A
  1. Contain sulfated GALACTOSE in position 1 (instead of glucuronic acid or iduronic acid)
  2. Most heterogenous regarding their sugars
  3. 2 Types Found in…
    a. ) KS-1: Cornea for transparency
    b. ) KS-2: (CCB) Cartilage, Connective Tissue, Bone
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89
Q

Describe Dermatin Sulfates:

A
  1. Contain a sulfated Iduronic Acid in position 1 (not Glucuronic Acid)
  2. Found in:
    a.) Heart Valve
    b.) Blood Vessels
    c.) Skin
    (HBS)
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90
Q

Describe Heparin Sulfates:

A
  1. Contains sulfated glucuronic OR iduronic acid at position 1
  2. Used for cell-cell recognition
  3. Found in:
    a. ) Basement Membranes
    b. ) Cell Surfaces
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91
Q

Describe Heparin:

A
  1. Contains MANY Iduronic Acid sulfates
  2. Is the GAG with the highest amount of sulfates and negative charges
  3. Acts as an ANTI-COAGULANT by facilitating the inhibition of thrombin to end the clotting process
  4. NOT extracellular (unlike heparin sulfate), instead its contained in GRANULES inside MAST CELLS lining arteries of the:
    a.) Lung
    b.) Liver
    c.) Spleen
    (Long Live Sulfates)
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92
Q

Describe the Bottle-Brush structure of GAG’s:

A
  1. GAG’s are NEGATIVELY charged, hydrated, and they REPEL each other (bottle brush)
  2. They are linked to a central CORE PROTEIN
  3. This allows 3 things:
    a.) Compressibility of Cartilage
    b.) Slippery consistency of Mucous
    c.) Sieve capability of ECM
    (Slippery Sieve Compress)
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93
Q

Describe the synthesis of Proteoglycans:

A

Done intracellularly
1. O-Glycosylation of core protein SERINE residues
2. Addition of Xylose and TWO galactose to form the linking region
3. Addition of REPEATING acidic sugar/amino sugar disaccharides
(OX-GD)
4. Then released into the ECM
Typically added using UDP-activated sugar derivatives

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94
Q

Synthesis of Acidic Sugars:

A
  1. Glucose is activated to UDP-Glucose
  2. UDP-Glucose is oxidized to UDP-Glucuronic Acid (Enzyme = UDP-Glucose DeHase)
  3. UDP-Glucuronic Acid is incorporated into GAG’s, and some remaining amount is epimerized into Iduronic Acid
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95
Q

Synthesis of Amino Sugars:

A
  1. Glucose is converted to Glucosamine-6-Phosphate
  2. Glucosamine-6-Phosphate is converted into:
    a. ) UDP-Glucosamine
    b. ) UDP-N-AcetylGlucosamine
    c. ) UDP-N-AcetylGalactosamine
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96
Q

What is the CENTRAL STRAND (not the core protein of an individual proteoglycan) of proteoglycan AGGREGATES?

A

Hyaluronic Acid

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97
Q

What bind each proteoglycan to the central strand?

A

LINK Proteins bind the CORE PROTEINS of each proteoglycan to the hyaluronic acid central strand

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98
Q

Describe Hyaluronic Acid:

A
  1. A special GAG that is NOT sulfated
  2. NOT covalently attached to a core protein
  3. Synthesized STEP-WISE in the ECM’
  4. Is the central strand for proteoglycan aggregates
  5. Connected to core proteins of each proteoglycan via LINK proteins
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99
Q

4 Locations of Hyaluronic Acid:

A
  1. Synovial Fluid of Joints
  2. Cartilage
  3. Loose Connective Tissues
  4. Vitreous Humor of the Eye
    (Sir Christopher Louis Valeriote)
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100
Q

Main Function of Hyaluronic Acid:

A

Facilitates Cell Migration In:

  1. ) Embryogenesis
  2. ) Morphogenesis
  3. ) Wound Repair
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101
Q

Describe Glycoprotein Structure:

A
  1. Contains mainly proteins, but also Oligosaccharides
  2. O-Linked Sugars are bound to -OH groups of Serine or Threonine
  3. N-Linked Sugars are bound to -N of Asparagine
  4. Carbohydrate component is SHORT and often branched
  5. MOST SERUM PROTEINS are glycoproteins, with the exception of ALBUMIN***
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102
Q

Describe Mucins:

A
  1. Special glycoproteins rich in carbohydrates (50%) instead of have just a small amount
  2. They attract water–>Provide SLIPPERY mucous
  3. They are O-glycosylated proteins with only ONE sugar linked to the -OH of Serine or Threonine
  4. N-AcetylGlucosamine binds ONE Sialic Acid (NANA) to result in mucins with MANY (-) charges***
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103
Q

Describe Blood Types:

A
  1. They are O-linked glycoproteins with side chains (R-groups) that are either a protein or a lipid (ceramide)
  2. Type O: No linkage to Galactose of the H substance (hence “zero” or “O”)
  3. Type A: Has an N-AcetylGalactose linked to the Galactose of the H substance
  4. Type B: Has a Galactose linked to the Galactose of the H substance
  5. Type AB: A mixture of Type A and Type B structures
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104
Q

What is the Glycocalyx composed of?

A
  1. Glycolipids

2. Glycoproteins

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105
Q

4 Functions of Glycocalyx:

A
  1. Cell-Cell recognition
  2. “Sieving” Barrier
  3. Inhibition of Platelet Adherence
  4. Prevention of Leukocyte adhesion
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106
Q

How can the glycocalyx attract unwanted binding?

A
  1. Viruses bind to glycoproteins, sometimes, as the first step of infection
  2. Bacterial toxins bind to glycolipids before entering a cell and colonizing
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107
Q

Describe the mechanisms of E. Coli and Heliobacter Pylori Infection:

A
  1. E. Coli attaches to MANNOSE residues that are in the membrane of CHEEK CELLS.
  2. Heliobacteri Pylori attaches to the GASTRIC surface and leads to ulcers by interaction with a blood group antigen of the gastric epithelium.
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108
Q

Describe N-inked Glycosylation of proteins:

A
  1. A mannose-rich oligosaccharide is synthesized while BOUND to Dolichol-PP that facilitates synthesis in the Rough ER.
  2. Dolichol-PP is a lipid containing many isoprene units and is BOUND to the Rough ER and it will transfer the mannose-rich precursor to a specific -N group of an ASPARAGINE residue of the protein.
  3. AT THE GOLGI = The mannose-rich oligosaccharide is modified to yield either:
    a. ) A high-mannose glycoprotein
    b. ) A complex glycoprotein
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109
Q

How is O-linked glycosylation different?

A

It involves INDIVIDUAL linkage of activated sugars step-wise to the Ser, Thr, and Hydroxylysine (collagen) -OH residues of a protein.

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110
Q

What are the 3 fates of Glycoproteins after modification of mannose-rich residues at the Golgi?

A
  1. Tagging with Mannose-6-Phosphate targets them to the Lysosome WHERE THEY BECOME LYSOSOMAL ENZYMES!!!! (Not Degraded)
  2. Release into the Extracellular space
  3. Incorporation into the cell membrane (glycocalyx)
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111
Q

What types of glycoproteins are likely to be degraded by the lysosome more often?

A

Those with lots of N-linked Glycosylation because they will be tagged with Mannose-6-Phosphate more easily

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112
Q

How do glycoproteins tagged with M6P make it to the lysosome to become active lysosomal enzymes?

A
  1. They are recognized by the M6P receptors in the Golgi, which package them into vesicles.
  2. Those vesicles are then destined to reach the Lysosome where the glycoproteins will become active.
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113
Q

Describe I-Cell Disease:

A
  1. “Lysosomal Storage Disease”
  2. Deficiency of the enzyme PHOSPHOTRANSFERASE, which adds the phosphate group to mannose residues of glycoproteins that would become lysosomal enzymes.
  3. No proteins receive the M6P marker, so the lysosomal enzymes are SECRETED from the cell instead of being sent to the lysosome.
  4. The lysosome of these cells is unable to degrade molecules efficiently so molecules accumulate and form INCLUSION BODIES (I-Cells).
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114
Q

What is the main difference between O-glycosylation and N-glycosylation?

A
  1. O-Glycosylation: Sugars are added DIRECTLY and unique for each protein.
  2. N-glycosylation: Mannose-Rich precursor is added to ALL proteins and they are modified later for specificity.
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115
Q

2 Components of Connective Tissue:

A
  1. Stroma: Supporting Structure

2. Parenchyma: Functional Unit

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116
Q

List the 5 PERMANENT residents of connective tissue:

A
  1. Fibroblasts
  2. Adipose Cells
  3. Macrophages/Monocytes
  4. Mast Cells
  5. Mesenchymal Stem Cells
    (MM FAM)
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117
Q

List the 5 TRANSIENT cell populations of connective tissue:

A
  1. Plasma Cells
  2. Lymphocytes
  3. Eosinophils
  4. Basophils
  5. Neutrophils
    (PELBN)
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118
Q

Fibroblasts:

A
  1. MOST COMMON cell type in connective tissue
  2. Synthesize FIBERS and GROUND SUBSTANCE
  3. Spindle-shaped
  4. Active = Fibroblast
    Inactive = Fibrocyte
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119
Q

Myofibroblasts:

A
  1. Possess contractile filaments

2. Wound healing involvement

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120
Q

How will active FibroBLASTS appear on an electron micrograph?

A
  1. rER substantial
  2. Extensive Golgi
  3. Euchromatic Nucleus
  4. Collagen fibrils outside the cell
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121
Q

Unilocular Adipocytes:

A
  1. One large fat droplet (typical WHITE fat cell)
    a. ) Organelles pushed to periphery
    b. ) Large fat inculsion
    c. ) Triglycerides = energy source
    d. ) RICH BLOOD SUPPLY
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122
Q

Multilocular Adipocytes:

A
  1. Many lipid droplets (BROWN fat)
    a. ) Central Nucleus
    b. ) Rich in MITOCHONDRIA
    c. ) Highly innervated
    d. ) Lipochrome pigments
    e. ) Produce HEAT
    f. ) RICH BLOOD SUPPLY
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123
Q

Macrophages:

A
  1. Derived from Monocytes
  2. Migrate to connective tissue and differentiate there
  3. Irregular Membrane/Cytoplasmic Extensions (pseudopodia)***
  4. Phagocytic –> Produce Cytokines
  5. Antigen-Presenting Cells
  6. MULTI-NUCLEAR, GIANT CELLS
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124
Q

Electron Micrograph of Macrophages:

A
  1. Large rER
  2. Prominent Golgi
  3. ABUNDANT LYSOSOMES***
  4. NUMEROUS PHAGOCYTIC VESICLES***
  5. Irregular outline of nucleus***
125
Q

What are the macrophages called in the Liver, Brain, and Bone respectively?

A
  1. Liver = Kupffer Cells
  2. Brain = Microglia
  3. Bone = Osteoclasts
126
Q

Mast Cells:

A
  1. Originate in bone marrow –> Precursors lack cytoplasmic granules
  2. Migrate to CT –> Prolif./Accum. of granules
  3. Derived from SAME progenitor as BASOPHILS
  4. Function: Granules store…Histamine, heparin, etc. and attract macrophages/eosinophils.
127
Q

Leukotrienes:

A
  1. The vasoactive PRODUCT of mast cells, NOT present in granules***
  2. Released from the cell as metabolite of arachidonic acid instead
128
Q

Mast Cells on Electron Micrograph:

A
  1. Large rER/Golgi

2. Granules containing histamine/heparin seen around periphery AND toward center of cytoplasm (lots)***

129
Q

Metachromasia:

A

Example: Mast cells when stained with a metachromatic dye that is BLUE, will stain a DIFFERENT color in response (i.e. PURPLE) once it binds to their granular material***

130
Q

Lymphocytes:

A
  • –>The B/T-Cells
    1. Small/SPHERICAL
    2. Almost no cytoplasm
    3. CONDENSED basophilic nucleus
    4. B-lymphocytes become Plasma cells
131
Q

Plasma cells:

A
  1. Synthesize/secrete a SINGLE class of antibodies
  2. Immunoglobulins = Glycoproteins
  3. HIGH rER (basophilic cytoplasm)
  4. “clockface Nucleus” (odd distribution)
  5. Golgi = slightly Acidophilic near nucleus
132
Q

Electron Micrograph of Plasma Cells:

A
  1. Large rER/Golgi

2. PROMINENT NUCEOLUS***

133
Q

Eosinophils:

A
  1. Red Granules in cytoplasm
  2. Bi-Lobed, condensed nucleus
  3. Phagocytosis of Antibodies
  4. Kill parasitic worms
134
Q

7 Components of the ECM:

A
  • –>FIBERS:
    1. Collagen
    2. Elastin
    3. Reticular
  • –>GROUND SUBSTANCE:
    4. GAG’s
    5. Glycoproteins
    6. Proteoglycans
  • –>OTHER:
    7. Tissue Fluid
135
Q

Collagen is considered _______ or acidophilic, and is formed _______ but assembled _____.

A
  1. Eosinophilic
  2. Intracellularly
  3. Extracellularly
136
Q

Where is Type 2 Collagen mostly found?

A

Hyaline and Elastic Cartilage

137
Q

Where is Type 5 Collagen found?

A
  1. Muscle
  2. Amnion/Chorion of Fetus
  3. Tendon Sheath
138
Q

Where is Type 3 Collagen mostly found?

A

Reticular fibers

139
Q

Reticular Fibers:

A
  1. SHORT, THIN, BRANCHING
  2. **Found in organs with large volume changes
    (i. e. Spleen, Arteries, Intestine, Testes, etc.)
  3. Stain with SILVER STAIN but will also be PAS (+) due to carbohydrate content
  4. Synthesized during WOUND HEALING
140
Q

List the 3 developmental stages of Elastic Fibers:

A
  1. Oxytalan
  2. Elaunin
  3. Elastic
141
Q

Differentiate between the 2 MAIN elastic fibers:

A
  • –>1. Elastin: A protein rich in:
    a. ) Glycine
    b. ) Proline
    c. ) Desmosine/Iso-desmosine
  • –>2. Fibrillin: A GLYCOprotein
142
Q

Where are elastic fibers found and what special staining do they require?

A
  • –>1. Found in:
    a. Large arteries
    b. Elastic cartilage
    c. Vocal ligament
    d. Bronchi
  • –>2. Stain with:
    a. Orcein
    b. Resorcin
    c. Verhoeff’s
143
Q

5 Main GAG’s of Connective Tissue:

A

(CCHHK)

  1. Chondroitin-4-Sulfate
  2. Chondroitin-6-Sulfate
  3. Hyaluronin
  4. Heparin Sulfate
  5. Keratin Sulfate
144
Q

4 Main Proteoglycans of Connective Tissue:

A

(Valeriotes are So Demi)

  1. Versican
  2. Aggrecan
  3. Syndecan
  4. Decorin
145
Q

4 Main Glycoproteins of Connective Tissue:

A

(Losers Only Fuck Themselves)

  1. Laminin
  2. Osteopontin
  3. Fibronectin
  4. Tenascin
146
Q

2 Things about Interstitial Fluid:

A
  1. Contains only a small quantity of water for solvation

2. Can accumulate EDEMA

147
Q

List the 3 Main types of Connective Tissue:

A
  1. Embryonic CT
  2. CT Proper
  3. Specialized CT
148
Q

2 Kinds of Embryonic CT:

A
  1. Mesenchyme

2. Mucous CT

149
Q

2 Kinds of CT Proper:

A
  1. Loose CT
  2. Dense CT
    a. ) Regular
    b. ) Irregular
150
Q

6 Kinds of Specialized CT:

A

(Real Cool, BABE)

  1. Reticular
  2. Cartilage
  3. Bone/Hemopoietic Tissue
  4. Adipose
  5. Blood
  6. Elastic
151
Q

Mucous CT:

A
  1. Few cells/fibers
  2. Mainly “jelly-like” ground substance
  3. Examples:
    a. UMBILICAL CORD
    b. Vitreous Humor
    c. Cardiac Jelly
152
Q

Mesenchyme:

A
  1. Sparse, spindle appearance

2. Give rise to many differentiated tissues

153
Q

Loose CT:

A
  • AREOLAR CT*
    1. Large number of cells
    2. Fills space between other tissues
    3. Flexible
    4. NOT rich blood supply
    5. NOT resistant to stress
154
Q

Dense IRREGULAR CT:

A
  1. Fewer cells than loose
  2. No orientation to collagen fibers
  3. HAS resistance to stress
  4. Found in:
    a. Periosteum
    b. Organ Capsules
    c. Dermis
    (Irregular Dense POD)
155
Q

Dense Regular CT:

A
  1. SPECIFIC orientation of collagen fibers
  2. Imparts tensile strength
  3. Found in:
    a. Tendons
    b. Ligaments
    (*DR LT. = Specific)
156
Q

Describe Endotendineum, Peritendineum, and Epitendineum:

A
  1. Endotendineum: CT that covers EACH fibroblasts (the cells that make up tendons)
  2. Peritendineum: CT that covers a GROUP of Fibroblasts
  3. Epitendineum: CT that covers the ENTIRE tendon
157
Q

Reticular CT:

A
  1. Reticular Cells = Modified Fibroblasts with extensions that cover reticular FIBERS
  2. Framework for myeloid and lymphoid organs
    (i. e. Bone Marrow and Lymph Nodes/Spleen)
  3. Short, thin, and branching
158
Q

Elastic CT:

A
  1. Yellow-colored*** Elastic Fibers
  2. Found in:
    a. Ligamentum Flavum
    b. Vocal Ligament
    c. Suspensory Ligament of the penis
    d. Arteries***
159
Q

Unilocular Adipose CT:

A
  1. WHITE FAT = Large cell with PERIPHERAL nucleus
  2. ONE big lipid droplet
  3. Function = Fat (energy) STORAGE
160
Q

Multilocular Adipose CT:

A
  1. BROWN FAT = Smaller cell with CENTRAL nucleus
  2. MANY lipid droplets
  3. Function = Fat (energy) RELEASE
161
Q

Ehlers-Danlos Syndrome:

A
  1. Abnormal collagen due to mutation in a gene encoding the alpha chains
  2. Results In: (Remember More TP, Honey)
    a. Rupture of blood vessels
    b. Morbidity/Mortality Early On
    c. Thin/Pale Skin
    d. Hypermobility of Joints/Digits
162
Q

Fibrosis/Keloids:

A
  1. Result from INCREASED Collagen
  2. After an injury, collagen involved in wound repair will form in excess causing:
    a. ) Hypertrophic scars: Raised, but within boundary of original wound site
    b. ) Keloid Scars: Extending into surrounding tissues
163
Q

Scurvy:

A
  1. Vit. C deficiency = No hydroxylation of Proline and Lysine by Prolyl and Lysyl Hydroxylase (using Vit. C to convert Fe3+ into Fe2+)
  2. No formation of H-bonds between alpha chains and no glycosylation of hydroxylysine residues
  3. Results in BLEEDING GUMS
164
Q

Marfan’s Syndrome:

A
  1. Decreased ELASTIC FIBERS (fibrillin, not elastin)
  2. Results In:
    a. Long, thin bones
    b. Arachnodactyly
    c. Aortic Aneurysm
    d. Mitral Valve Prolapse
165
Q

Anaphylactic Shock:

A

Increased MAST CELL release of Histamine

166
Q

Definition of a drug:

A

Any substance that, when administered to a living organism, produces a biological effect

167
Q

Differentiate between Pharmacokinetics and Pharmacodynamics:

A
  1. KINETICS: (Body on Drug) Study of Absorption, Distribution, Metabolism, and Excretion of the drug
  2. DYNAMICS: (Drug on Body) Study of effects OF the drug and their mechanisms of action.
    * (Kinetic people have a good “BOD”)*
168
Q

Differentiate between Pharmacotherapeutics/Clinical Pharmacology and Pharmacotherapy:

A
  1. Pharmacotherapeutics: The STUDY of the use of drugs in prevention/treatment of a disease.
  2. PharmacoTHERAPY: The ACTUAL USE of drugs in treatment of a disease.
169
Q

Toxicology:

A

The study of the adverse effects of drugs on the body

170
Q

Although drugs can stimulate/inhibit normal cellular functions, what can’t they do?

A

ADD functions that don’t exist already

171
Q

What is a “drug receptor/target”? What, typically, are these structures?

A
  1. Any component of a cell that a drug interacts with to elicit its intended effect
  2. PROTEINS
172
Q

3 Examples of Drugs that alter ION CHANNELS:

A

(Anything Like Sedatives)

  1. Anti-epileptics
  2. Local Anesthetics
  3. Sedatives/Hypnotics
173
Q

Most drugs act by binding to _______.

174
Q

4 responses mediated by cAMP:

A

(BRIB)

  1. Breakdown of Glycogen in Liver
  2. Relaxation of Smooth Muscle
  3. Increased HR/Contractile Force
  4. Breakdown of Triglycerides in Adipose
175
Q

5 responses mediated by Ca2+:

A

(SHINS)

  1. Smooth Muscle Contraction
  2. Hormone Release
  3. Increased Contractile force of Cardiac Muscle
  4. Neurotransmitter Release
  5. Secretion from exocrine glands
176
Q

2 Types of Enzyme-Linked receptors:

A
  1. Ligand-Regulated Transmembrane Receptors
    Ex: Insulin, GPCR’s, etc.
  2. Cytokine Receptors
177
Q

Name another Tyrosine-Kinase Receptor besides Insulin:

A

EGFR: Epidermal Growth Factor Receptor

178
Q

Describe how Tyrosine Kinase Receptors Function:

A
  1. Ligand Binds–> Causes Dimerization of subunits
  2. Receptor subunits auto-phosphorylate Tyrosines of their ICD
  3. Intracellular signaling proteins BIND these phosphorylated Tyrosines
  4. They activate a signaling cascade that results in regulation of transcription
179
Q

How are Cytokine Receptors different from Ligand-regulated Transmembrane Enzymes (Like the insulin receptor)?

A

They bind intracellular Tyrosine Kinases, but they use the JAK-STAT pathway (Janus-Kinase)

180
Q

Give 3 examples of things that use Cytokine Receptors:

A

Peptide Molecules:

  1. Growth Hormone
  2. Erythropoietin
  3. Interferons
181
Q

Describe the Cytokine Receptor pathway:

A
  1. Ligand binds –> Causes dimerization of subunits
  2. They auto phosphorylase each other’s JAK’s
  3. JAK’s are bound by STAT, and they get phosphorylated
  4. Then STAT’s dimerize and translocation to the nucleus to regulate transcription
182
Q

Describe Nuclear Receptors:

A
  1. They are Ligand-Activated Transcription factors

2. Contain a ligand-binding domain AND a DNA-binding domain

183
Q

3 Examples of Nuclear Receptor Ligands:

A
  1. Steroids
  2. Thyroid hormone
  3. Vitamin D
184
Q

Where is brown fat typically found?

A

In neonates, because they can’t regulate temp well. So it is located around the neck, abdomen, and around the adrenal glands

185
Q

Give an example of a drug class that affects a Transporter to elicit its effect:

A

SSRI’s: Inhibit serotonin re-uptake transporters

186
Q

Give an example of a drug that doesn’t act on any receptor at all to elicit its effect:

A

Antacid: Acts on gastric acid directly

187
Q

Differentiate between the two types of dose response curved:

A
  1. Graded: Measures the EC50 (concentration at which 1/2 of the Emax is reached) or Kd of a drug (concentration at which 1/2 of total receptors for the drug are bound)
  2. Quantal: Measures the ED50 (concentration at which the effect is produced in 50% of all animals it’s used on) and LD50 (concentration at which it is lethal to 50% of all animals it’s used on)
188
Q

When will a plot of drug effect/binding be represented by a hyperbolic curve?

A

When the X-axis is simply Concentration, rather than Log Conc.

189
Q

What does it mean if the EC50 of a drug (the concentration required to exhibit half the maximal effect) is LOWER than the Kd of the drug (the concentration required to bind half the total receptors)?

A

It means that the drug doesn’t have to occupy all of its receptors to invoke the max response, so it has “spare receptors” BECAUSE the signal has been amplified

190
Q

Give an example of a receptor that exhibits signal amplification:

A

Beta-Adrenergic Receptors

191
Q

Differentiate between Efficacy and Potency:

A

Efficacy: A measure of how much of an effect a drug CAN produce maximally, regardless of how much drug it requires (Calculated with Emax)
Potency: A measure of how MUCH of the drug is required to produce an affect of a certain magnitude. (Calculated with EC50)

192
Q

Describe the effects of the 3 kinds of RECEPTOR Antagonism:

A
  1. Reversible Competitive Antagonism: Higher EC50
  2. Irreversible Competitive Antagonism: Lower Emax
  3. Noncompetitive Angagonism: Lower Emax
193
Q

Describe the mechanisms of the 3 kinds of NON-RECEPTOR Antagonism:

A
  1. Indirect Functional Antagonism: Drug binds to something else in the pathway activated by the agonist it wishes to inhibit. Example = Binding/Blocking PKA to inhibit B-adrenergic agonists
  2. Physiological Functional Antagonism: One drug OPPOSES another by binding a different receptor. Example = Epinephrine Receptor (EpiPen use) binding decreases BP and causes bronchodilation to oppose histamine effects
  3. Chemical Antagonism: Antagonist reacts chemically WITH the agonist directly to form an inactive product. Example = Protamine (+ charged) binds and inactivated Heparin (- charged) to allow coagulation
194
Q

Compare Full Agonists and Partial Agonists:

A

Full: Produce a maximal response (every binding event causes the intended response)
Partial: Produces a sub maximal response (not all binding produces the intended response)

195
Q

How can partial agonists act as competitive ANTAGONISTS?

A

If they are added in the presence of a full agonist, they will not produce a response as often as the full agonist would alone, so it INCREASES the EC50

196
Q

What is it called when a receptor exhibits some response in the absence of any agonist?

A

Constitutive Activity

197
Q

What is an Inverse Agonist?

A

Meets the definition of an agonist because it produces a response when it binds the receptor, but they bind CONSTITUTIVE receptors so their response is REVERSING their constitutive activity.
(I.e. They act more like antagonists)

198
Q

How do inverse agonists potentially have worse effects than antagonists?

A

When an antagonist binds a receptor, it prevents a response from happening so no effect is produced. But when an inverse agonist binds a constitutive receptor, it REDUCES the effect that was naturally in place.

199
Q

Drugs are not considered to have specific binding, but rather ______.

A

Selective Binding: They bind more than one receptor

200
Q

When is a drug considered “selective”?

A

When there is at least a TEN FOLD difference between its binding affinity (Kd or EC50) for its first target (The one that produces THERAPEUTIC effects) and it’s second target (the one that produces ADVERSE effects)
(I.e. Greater difference —> MORE selective!!

201
Q

How does the effect of a drug with 10-fold selectivity compare to that of a drug with 100-fold selectivity?

A

There is little to no clinical significance because they’re basically both producing effects at Emax

202
Q

Differentiate between Desensitization/Tachyphylaxis and Tolerance:

A
  1. Desensitization/Tachyphylaxis: Quickly, but gradually diminishing effect of a drug when given CONTINUOUSLY or REPEATEDLY (seen within minutes)
  2. Tolerance: Slower, more gradual diminishing of drug effect after continued administration over time (days or weeks)
203
Q

Define Drug Resistance:

A

Loss of Effectiveness of Antimicrobial or Anti-Tumor drugs (I.e. LOWER Emax, compared to Tolerance which leads to HIGHER EC50)

204
Q

Refractoriness:

A

Loss of Therapeutic Efficacy (less selective?)

205
Q

Describe the 5 ways Desensitization can occur:

A
  1. Change in Receptor: GPCR gets phosphorylated and can’t produce response as well.
  2. Internalization of Receptor: Endocytosis due to prolonged exposure.
  3. Exhaustion of Mediators: The molecule binding the receptor is depleted.
  4. Increased Metabolic Degradation: Repeated administration lowers plasma concentration.
  5. Physiological Adaptation: Opposition by a homeostatic response.
206
Q

How is the TD50 different from the ED50?

A

It measures the concentration at which a TOXIC effect is produced in 50% of all animals it’s used on

207
Q

What is plotted on a Graded Dose Response Curve versus a Quantal Dose Response Curve respectively?

A
  1. Graded: “% of Max Effect” vs “Log Conc.” —> Sigmoid

2. Quantal: “%Effected” vs “Dose” —> Sigmoid

208
Q

What is the Therapeutic index and how is it calculated?

A
  1. The ratio of TD50 (or LD50) to ED50.
  2. Calculated As:

TI = TD50 / ED50
Or
TI = LD50 / ED50

209
Q

Is it high or low Therapeutic Index good for a drug?

A

A very HIGH TI is good because that means it takes a LARGE dose to produce toxic or lethal effects, while it only takes a SMALL dose to produce the desired, therapeutic effect.

210
Q

What is a more clinically significant index of safety for using a drug than the Therapeutic Index?

A

The Therapeutic Window: The difference between the Minimum Therapeutic Concentration and the Minimum Toxic Concentration.
(I.e. It tells you the safety range in which ONLY therapeutic effects will be seen. NOTE: It does not use TD50 or ED50, but TDmin and EDmin instead)

211
Q

Describe the structure of skin:

A

Skin = “Cutis”

  1. Epidermis: Strat. Squ. Ker. Epi.
  2. Dermis: Has 2 Layers…
    a. ) Loose CT, followed by…
    b. ) Dense Irreg. CT
  3. Hypodermis: Subcutaneous tissue
212
Q

List 5 specialized features of skin, and tell which ones are ONLY seen in thin skin:

A

(Suck My Hairy Nut Sack)

  1. Sweat Glands
  2. Mammary Glands
  3. Hair Follicles/Hair (THIN ONLY)**
  4. Nails
  5. Sebaceous Glands (THIN ONLY)**
213
Q

List the 5 Layers of the Skin and tell which one only belongs to thick skin:

A
  1. Stratum Corneum: DEAD, keratinized cells
  2. Stratum Lucidum: THICK ONLY**
  3. Stratum Granulosum: Cells about to die
  4. Stratum Spinosum: Maturing/Slowly dying cells
  5. Stratum Basale: Cells that CAN differentiate
214
Q

List the 4 types of Epidermal Cells:

A

(Made it to the top “LK MK”)

  1. Keratinocytes
  2. Melanocytes
  3. Langerhan’s Cells
  4. Merkel Cells
215
Q

Keratinocytes:

A
  • PREDOMINANT IN EPIDERMIS*
    1. Attached to each other by DESMOSOMES and to the basal lamina by HEMI-DESMOSOMES
    2. Originate in the Stratum Basale
    3. Produce Keratin that STRENGTHENS the cells as they move through each layer upward
    4. ALSO produce Lamellar bodies: Act as water barrier
216
Q

Describe the special cell death of keratinocytes:

A

They are sloughed off from the stratum corneum, which is programmed and regulated by PROTEOLYTIC activity on the DESMOSOMES.

217
Q

What 2 things do keratinocytes produce?

A
  1. Keratin: Provide strength

2. Lamellar Bodies: Provide water barrier

218
Q

Melanocytes:

A
  1. Dendritic Cells derived from Neural Crest
  2. Found in Stratum BASALE
  3. CLEAR, with LARGE, ELONGATED nuclei
  4. Processes extend between keratinocytes
  5. NO DESMOSOMES, only HEMI-DESMOSOMES
  6. Multiply throughout life
  7. CYTOCRINE Secretion: Transfer melanin TO surrounding Keratinocytes: Giving them UV protection
219
Q

What is skin color dependent on?

A

Amount of MELANIN, and NOT MELANOCYTES.

220
Q

Synthesis of Melanin:

A

Tyrosine is oxidized to DOPA, which then becomes Melanin

221
Q

What is melanoma and how is it diagnosed?

A
  1. Tumor formed by proliferating melanocytes
  2. The ABCDE rule:
    A = Asymmetry
    B = Border
    C = Color
    D = Diameter
    E = Evolving
222
Q

Merkel’s Cells:

A
  • LEAST NUMEROUS*
    1. Also dendritic cells, detect TOUCH sensation
    2. Most abundant in fingertips
    3. Have desmosomes AND contain keratin filaments
    4. Nucleus is LOBED
    5. Neuro-secretory granules to relay sensory info to Afferent Nerve Fibers
223
Q

Langerhan’s Cells:

A
  • Originate from CLP: Common Lymphoid Progenitor*
    1. Antigen-Processing Cells
    2. (APC’s) - Antigen-PRESENTING Cells
    3. Migrate to lymph nodes to present encountered antigens to the T-cells
    4. NO DESMOSOMES OR HEMI-DESMOSOMES
    5. DARK BLUE staining Nucleus, with CLEAR cytoplasm
    6. Dendritic processes (like Melanocytes)
    7. Involved in Delayed-Type Hypersensitivity Reactions
224
Q

Key Feature of Langerhan’s cells on TEM:

A

Possess BIRBECK granules: Vesicles that have a tennis racket shape

225
Q

How do Langerhan’s Cells present antigens to the T-cells?

A

They use MHC 1/2 AND IgG receptors to carry the antigen to the T-cells

226
Q

Stratum Basale:

A
  1. Simple Cuboidal Epithelium
  2. Posesses 3 types of cells:
    - –>a. Keratinocyte Stem Cells
    - –>b. Merkel’s Cells
    - –>c. Melanocytes
  3. Closely packed nuclei, less cytoplasm
  4. INTENSELY BASOPHILIC***
  5. LOTS of Melanin Granules
  6. Extensive desmosomes (to other cells) and hemi-desmosomes (to basal lamina)
227
Q

What does the term Stratum Germinativum imply?

A

It explains that the Stratum Basale is the origin of Keratinocyte stem cells

228
Q

Stratum Spinosum:

A
  • Prickle Layer*
    1. Many processes or “spines”
    2. Several layers thick, becoming MORE FLATTENED as they move upward
    3. As this happens, Nuclei change from Ovoid —> ELONGATED
    4. Only DESMOSOMES between them that are called “Nodes Of Bizzozero”***–> Appear as a slight thickening
229
Q

Stratum Granulosum:

A
  • MOST SUPERFICIAL of the Non-Keratinized Cells*
    1. ONE to THREE layers thick
    2. Conspicuous granules containing KERATOHYALIN: Irregularly-shaped granules with INTENSELY BASOPHILIC staining
    3. They allow AGGREGATION of KERATIN filaments
    4. They ALSO contain granules of Lamellar Bodies for water protection
230
Q

Describe Keratohyalin:

A
  1. Cystine and Histidine rich molecules that are precursors for FILAGRIN
  2. They allow aggregation of Keratin filaments in epidermal cells
231
Q

Describe the Epithelial Water Barrier:

A
  1. Cell Envelope: MECHANICAL barrier, with insoluble proteins on its inside
  2. Lipid Envelope: Outer Layer of the two and of the cell overall, containing Lamellar Body contents excreted by Stratum Spinosum/Granulosum
232
Q

Stratum Lucidum:

A

(Thick skin ONLY)

  1. Appears as an EOSINOPHILIC BAND upon ETM
  2. Well-advanced keratinization
233
Q

Stratum Corneum:

A
  1. NO organelles or nuclei
  2. Deeper portion contains the WATER BARRIER
    (i. e. the plasma membranes are not only thicker, but also covered with an EXTRA lipid layer containing lamellar bodies
  3. TONOFIBRILS: aka Aggregates of Keratin Filaments
  4. ABRUPT transition from Granular Layer
  5. Variable # of layers
234
Q

Tonofibrils:

A

Aggregates of keratin filaments in keratinocytes that are CREATED by keratohyalin (secreted from irregular-shaped granules in Stratum Granulosum)

235
Q

Describe Keratinization:

A
  1. Cells LOSE their organelles/cytoplasm/nuclei
  2. Form more TONOFILAMENTS
  3. FILAGRIN (formed from keratohyalin) then joins the tonofilaments into FIBRILS
  4. Upon reaching the outermost layer of stratum corneum cells, the desmosomes are BROKEN and cells are sloughed off
236
Q

Role of Keratohyalin vs Filagrin:

A
  • —->Keratohyalin:
    1. Synthesized in irregular-shaped granules in stratum granulosum
    2. Aggregates keratin filaments into TONOFIBRILS
  • —->Filagrin:
    1. Synthesized from Keratohyalin produced in Stratum Granulosum Irregular-shaped granules
    2. Arranges TONOFIBRILS into FIBERS
237
Q

Psoriasis:

A
  1. HIGH turnover of keratinocytes (forms dandruff on scalp in mild cases)
  2. Presents With:
    a. Scaly Appearance
    b. White patches of cornified skin over raised/red areas
238
Q

Dermal Papillae:

A

Convoluted/Invaginated-appearing regions of the boundary between epidermis:dermis EXTENDING into the epidermal layer, because the separation between the epidermis and dermis is uneven

239
Q

Epidermal (Rete) Ridges:

A

Infoldings from the epidermis that compliment the dermal papillae extending into the epidermis

240
Q

What cells might have longer dermal papillae and much deeper epidermal ridges?

A

Cells that are subject to high mechanical stress, so these are needed for greater interface between the epidermis and dermis

241
Q

Describe the basic structure of the Dermis:

A

Composed of 2 Layers:

  1. Papillary Layer: (LOOSE CT)
  2. Reticular Layer: (DENSE IRREG. CT)
242
Q

List the structures found in the Papillary layer of the dermis:

A
  1. Blood Vessels
  2. Meisner’s Corpuscles (Nerve corpuscles)
  3. Fine Elastic Fibers
  4. Collagen Type 1 and 3
243
Q

List the structures found in the Reticular layer of the dermis:

A
  1. Irregular, thick bundles of Type 1 collagen

2. Course Elastic Fibers

244
Q

Which layer of the skin gives it elasticity?

A

The Dermis (probably more specifically the papillary layer)

245
Q

Describe the Hypodermis:

A
  1. Contains a layer of ADIPOSE tissue called the Panniculus Adiposus
  2. Provides INSULATION and ENERGY STORAGE
    (extra thick in those who live in cold climates)
  3. Also contains associated CT, together these layers form the Hypodermis (or Subcutaneous Fascia)
  4. Contains:
    a. Hair follicles
    b. Glands
    c. Mechanoreceptors
246
Q

Describe the 3 types of Epithelial Appendages for skin:

A

ALL originate in the dermis and are outgrowths of the epidermis
1. Hair Follicles
2. Nails
3. Glands
a. Eccrine (Sweat)
b. Sebaceous
c. Apocrine
(SHANE)

247
Q

Hair Follicles:

A
  1. Invagination of epithelium that extends into the HYPODERMIS
  2. ***Phlebo Sebaceous Organs: They are associated with sebaceous glands AND smooth muscle
  3. NOT FOUND IN THICK SKIN
  4. Components:
    a. Infundibulum: UPPER region ABOVE the sebaceous gland entry region
    b. Isthmus: Between sebaceous gland entry and bulb
    c. Inferior Segment: Suprabulbar/Bulbar region
  5. BULB contains the matrix for hair formation (and melanocyte stem cells)
248
Q

What is the Keratogenous zone of the hair follicle?

A

The region just after the matrix where keratinization of the HAIR and INTERNAL ROOT SHEATH occur

249
Q

What is the Glassy of hair?

A

The thick basal lamina of hair that separates it from the internal root sheath and the underlying dermis as it moves toward the surface and keratinizes

250
Q

How is the color of hair determined?

A

By the amount of melanin produced by the melanocytes in the BULB

251
Q

Describe the 3 layers of hair:

A
  1. Medulla: (INNERMOST layer) ONLY present in thick hair, and central part contains large, vaculated cells
  2. Cortex: (MIDDLE) Contains cuboidal cells that undergo keratinization
  3. Cuticle: (OUTERMOST layer) Contains squamous cells
252
Q

What smooth muscles are the hair follicles associated with?

A

Arrector Pili muscles (that make hair stand on end)

253
Q

Describe Nails:

A
  1. Hard PLATES of keratinized cells
  2. Rest on a NAIL BED:
    a. ) Nail Matrix: Beginning of Nail plate/Bed (behind everything)
    b. ) Hyponysium/Hyponychium: (End of Nail plate/Bed)
    c. ) Lunula: Exposed/visible part of nail matrix NOT protected by the eponychium
254
Q

Describe Sebaceous glands:

A
  1. Simple, Branched Acinar Glands
  2. Holocrine secretion into DEEPER DERMIS
  3. Opens INTO HAIR FOLLICLE
  4. Secrete SEBUM: Is CLEAR with H&E staining and helps prevent hair from becoming dry and brittle
255
Q

Describe Sweat Glands:

A
  1. Simple, Coiled/Tubular Glands
  2. Stratified Cuboidal DUCTS (with a basal and luminal layer)
  3. Secretion into DEEP DERMIS
  4. Has 3 Types of Cells:
    a. CLEAR cells: Lots of glycogen (stains with PAS)
    b. DARK cells: Lots of rER/secretory granules (H&E)
    c. Myoepithelial cells: BASAL aspect OF the secretory segment–> Contract to expel secretions of sweat!
  5. Ducts pass all the way through dermis and SPIRAL through the epidermis ONTO SURFACE
256
Q

Describe Apocrine Glands:

A
  1. Found ONLY in armpit and perineum (taint)
  2. Coiled, Tubular Glands
  3. Secretory portion in Dermis or even HYPODERMIS
  4. LARGER SECRETORY LUMEN than other glands
  5. Secrete Pheromones***–>Via MEROCRINE secretion, but the duct opens INTO the hair follicle
  6. Ducts are STRAIGHT with Strat. Cuboidal Epi.
257
Q

3 Things innervated by Secretomotor Nerve Endings:

A
  1. Blood Vessels
  2. Errector Pili
  3. Sweat Glands
258
Q

3 Kinds of Encapsulated Nerve Endings:

A
  1. Pacinian Corpuscles: Sense PRESSURE CHANGES and VIBRATIONS
  2. Meisner’s Corpuscles: Sense LIGHT TOUCH
  3. Ruffini Endings: Sense STRETCH and TORQUE
259
Q

What 2 other kinds of nerve endings are there?

A
  1. Free Nerve Endings

2. Merkel’s Corpuscles

260
Q

Describe Free Nerve Endings:

A
  • MOST NUMEROUS*
    1. Terminate in the Str. Granulosum
    2. NO MYELIN or CT
    3. They detect:
    a. Fine Touch
    b. Heat/Cold
    4. Surround hair follicles and attach to their OUTER root sheath –> ACT AS MECHANORECEPTORS
261
Q

Describe Pacinian Corpuscles:

A
  1. LARGE and Ovoid in the DEEP DERMIS or HYPODERMIS
  2. MYELINATED nerve endings that are encapsulated
  3. Inside capsule = No myelin Sheath, but instead surrounded by FLATTENED SCHWANN CELL LAMELLAE
  4. Remainder of core is formed by CONCENTRIC lamellae
262
Q

Describe Meisner’s Corpuscles:

A
  1. Tapered CYLINDERS that are PERPENDICULAR to the skin surface
  2. Just above the dermal papillae***
  3. Nerve Endings follow a SPIRAL path into the corpuscle
  4. FLATTENED SCHWANN CELLS with IRREGULAR lamellae along the axon in the corpuscle
263
Q

Describe Ruffini Endings:

A
  1. Simplest corpuscles, have elongated shape
  2. THIN CT surrounding a fluid-filled space
  3. Collagen fibers from the surrounding CT pass THROUGH it
  4. Single, myelinated fibers enter the capsule and terminate in knob-like bulbs***
  5. Dispersed/Inter-twined axonal endings within capsule
  6. Sense STRETCH/TORQUE via responding to COLLAGEN DISPLACEMENT BTWN THEM***
264
Q

Difference between 3 classes of Burns:

A

1st Degree: Affects Epidermis
2nd Degree: Affects Epidermis AND Dermis
3rd Degree: Affects Epidermis, Dermis, AND Hypodermis

265
Q

Differentiate between Aqueous and Lipid Diffusion of a drug:

A

Aqueous: PARAcellular Pathway
Lipid: TRANScellular pathway

266
Q

Define Transcytosis:

A

Endocytosis OR Exocytosis

267
Q

Pros/Cons of Oral Absorption:

A

Pro: Most Convenient
Con: First Pass Effect (A fraction is metabolized in the gut wall and liver before reaching circulation

268
Q

List the 3 Parenteral Route of Administration:

A
  1. IM
  2. SUB-Q
  3. INTRA-DERMAL
269
Q

Effect of P-Glycoprotein:

A

An ATP-dependent cell membrane pump that prevents accumulation of drugs by causing their efflux from their target cells

270
Q

How does pH affect the absorption of a drug?

A

Drugs typically exist in both an ionized and non-ionized form, and a change in pH may convert more of the drug to the IONIZED form which cannot cross lipid membranes.

271
Q

Would “HA” or “A” be considered the ionized form of a drug?

What about “HB” versus “B”?

A

A- (the DE-protonated form)
BH+ (the protonated form)
These are the CHARGED versions that WONT cross

272
Q

Describe the Henderson Hasselbach Equation in relation to drug absorption:

A

pH - pK = log [unprotonated] / [protonated]

So when pH = pK, then both concentrations are EQUAL

273
Q

How can the H-H equation be applied?

A

If a drug is more in the liposoluble form in the RENAL TUBULES, then a high amount will be reabsorbed!
This is called ION TRAPPING

274
Q

Explain how Ion Trapping can be done:

A

If you want to excrete more of a drug, you can adjust the pH of the urine so that it will be in an aqueous, ionized state during its passage through the kidney.
I.e. TRAPPED in the tubules and excreted!

275
Q

How would you adjust the urine pH to excrete weak acids and weak bases respectively:

A

Weak Acids: Make urine more ALKALINE

Weak Bases: Make urine more ACIDIC

276
Q

What will increase absorption of an oral drug?

A

Any factor that stimulates GASTRIC EMPTYING, because most absorption will occur in the small intestine

277
Q

What is another name for P-Glycoprotein?

A

MDR-1 (Multi Drug-resistant Receptor 1)

278
Q

Define Bioavailability:

A

The amount of an administered drug that reaches the systemic circulation (and is therefore available)

279
Q

How is bioavailability calculated?

A

*AUC = Area Under Curve for a plot of the drug concentration over time

[AUC of Route Used / AUC IV] x 100

280
Q

Define Drug Distribution:

A

The process of the drug LEAVING circulation to enter the ECF or target tissue

281
Q

4 Factors that affect Distribution:

A
  1. Hydrophobicity
  2. Bound/Unbound to Plasma Proteins
  3. Capillary Permeability
  4. Blood Flow
282
Q

What organs to drugs get distributed to first?

A

Liver, Kidneys, and Brain (highly perf used organs). MUCH SLOWER in muscle, skin, fat, and viscera

283
Q

Which plasma proteins to ACIDIC and BASIC drugs bind respectively?

A

Acidic: ALBUMIN
Basic: alpha-1-acid Glycoprotein

284
Q

When is a drug pharmacologically active?

A

When it’s in the UNBOUND form

285
Q

What is an example of how interference with drug binding to its plasma protein can cause an adverse effect?

A

Sulfonamides: Compete with bilirubin for albumin binding and cause BILIRUBIN ENCEPHALOPATHY

286
Q

Which nerve endings/corpuscles detect pain?

A

FREE nerve endings

287
Q

How can accumulation of drugs be a problem?

A

Liposoluble drugs can accumulate in fat and remain there to act as a RESERVOIR of that drug to prolong drug action

288
Q

2 Features of the BBB that make it resistant to drug effects:

A
  1. Astrocyte END FEET surround the brain capillary endothelial cells
  2. P-Glycoprotein pumps drugs back into the blood
289
Q

What is the consequence of having such a good safeguard system of the BBB?

A

Drugs that we want to cross it must have:

  1. High Liposlubility
  2. Active Transporters
290
Q

What 2 processes allow drug elimination?

A
  1. Metabolism

2. Excretion

291
Q

In order to make a drug more readily excreted, it must be made more ______.

A

HYDROPHILIC

292
Q

Describe the 4 methods of Biotransformation:

A
  1. Active –> Inactive
  2. Unexcretable DRUG–> Excretable METABOLITE
  3. Active DRUG –> Active or Toxic METABOLITE
  4. Inactive –> Acitve
293
Q

Phase 1 Metabolism:

A
  1. Deamination
  2. Oxidation/Reduction
  3. Hydroxylation
  4. Decarboxylation
    Increases Hydrophilicity and converts to an active or inactive metabolite
294
Q

Phase 2 Metabolism:

A 
Covalent bonds with:
1. Glucuronic Acid
2. Glutathione
3. Amino Acids
4. Acetate
5. Sulfate
Convert metabolites to CONJUGATES for elimination
295
Q

Besides the liver and kidneys, what other organs detoxify drugs?

A
  1. Skin
  2. Lungs
  3. GI Tract
296
Q

Where are the enzymes for Phase 1 and 2 metabolism found in the cell respectively?

A

Phase 1: In the ER

Phase 2: In the Cytoplasm

297
Q

What enzyme catalyze a most Phase 1 reactions?

A

Cytochrome P450

298
Q

Describe Cyt P450:

A

A Superfamily of Heme Proteins

There are many kinds, but the MAIN one is CYP3A4 in the liver***

299
Q

Which Cytochrome families are mainly involved in metabolizing Xenobiotics?

A

Families 1-3

300
Q

Give 3 examples of drugs that INDUCE Cytochrome P450 expression:

A
  1. Phenobarbital
  2. Rifampin
  3. Carbamazepine
301
Q

Give an example of how Xenobiotics induce CYP450’s to alter another drugs metabolism or its own:

A

St. John’s Wort: Binds to XENOBIOTIC RECEPTOR on HEPATOCYTES and induces CYP450 enzymes to metabolize Indinavir

302
Q

Give 4 examples of drugs that INHIBIT CYP450 enzymes:

A
  1. Cimetidine
  2. Erythromycin
  3. Chloramphenicol
  4. Grapefruit Juice
303
Q

Give an example of a drug that is metabolized to an ACTIVE metabolite that can cause toxic effects:

A

Acetaminophen

304
Q

Describe the 3 types of genetic variations within individuals that can affect their drug metabolism:

A
  1. Pharmacokinetic Variation: Affects metabolic proteins or transport proteins
  2. Pharmacodynamic Variation: Affects drug targets or target pathway molecules
  3. Idiosyncratic Effects
305
Q

Mechanism of Grapefruit Juice:

A
  1. Inhibits CYP3A4
  2. ALSO inhibits P-Glycoprotein
    * IN THE SMALL INTESTINE*
306
Q

Describe 3 examples of how environmental factors influence drug metabolism:

A
  1. Cigarette Smoke: AhR-mediated (Aromatic Hydrocarbons) induction of CYP450’s
  2. Charcoal: Induction of CYP1A
  3. Pesticides: Speeds up metabolism of certain drugs
307
Q

Though most drugs are excreted renaly, how are some others excreted?

308
Q

List the 3 processes involved in renal excretion:

A
  1. Glomerular Filtration
  2. (ACTIVE) Tubular Secretion
  3. (PASSIVE) Tubular Reabsorption
309
Q

Difference between Topical and Transdermal:

A

Topical: Used to treat THE SPECIFIC SPOT that it was placed on
Transdermal: Intended to treat a DISTANT target, and travel away from the skin where it was administered

Term 1 (8 decks)

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