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3152 > IC7 & IC8 > Flashcards

IC7 & IC8 Flashcards

1
Q

Usual body protein size

A

6-8 kDa

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2
Q

MW of proteins more than ____ may be eliminated via phagocytosis

A

200 kDa

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3
Q

Intestinal epithelium generally carries_____ charges

A

negative

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4
Q

Is convection affected by MW?

A

not affected by MW unless proteins are enormously large & gets trapped in ECM

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5
Q

Convection may be influenced by _______

A

steric hindrance & charge interactions

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6
Q

Larger proteins ____ move slowly across capillary membrane

A

> 16-20kDa

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7
Q

Are proteins metabolised by liver?

A

No, they are poor CYP substrates. Mostly metabolised via proteolysis.

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8
Q

Charge of glomerular basement membrane

A

Negative

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9
Q

Which protein sizes cannot be renally eliminated?

A

Proteins > 50 kDa not eliminated renally

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10
Q

Should vaccines be PEGlyated?

A

No, because we want immunogenicity

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11
Q

Ways to incr protein half-life

A
  1. Glycosylation of proteins
  2. PEGylation
  3. Incr size by means of fusion proteins
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12
Q

Two pathways in which proteins are degraded in mammalian cells

A
  1. Lysosomal pathway
  2. Proteasomal pathway
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13
Q

Normal levels of HIF-1alpha at normoxia

A

Low

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14
Q

Under normoxic conditions, HIF-1alpha is hydroxylated by oxygen-dependent _______

A

prolylhydroxylases

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15
Q

What happens to hydroxylated HIF-1alpha?

A

It gets recognized and targeted for ubiquitination

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16
Q

Role of HIF-1 alpha

A

A transcription factor responsible for oxygen homeostasis during hypoxic conditions; induces expression of genes involved in angiogenesis, cell migration and glycolytic pathway

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17
Q

Is lysosomal degradation a specific process?

A

No, as long as proteins are in lysosomes, regardless of identity, they are degraded.

(In higher eukaryotes, only membrane-associated proteins and alien proteins internalized by endocytosis are degraded in lysosomes.)

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18
Q

Is proteasomal degradation a specific process?

A

Yes, it takes place for ubiquitinated or some non-ubiquitinated proteins.

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19
Q

Is pinocytosis a specific process?

A

No

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20
Q

Role of 26 proteasome

A

responsible for specific degradation of regulatory proteins and removal of damaged proteins

21
Q

Composition of 20s core structure of 26 proteasome

A

4 heptameric rings: 2 alpha outer subunits + 2 beta inner subunits

22
Q

Structure of 26 Proteasome

A

20S core particle capped by a 19S regulatory particle at one or both ends

23
Q

Inner rings of 26 proteasome house a central cavity containing ________

A

proteolytic active sites

24
Q

Ubiquitin tag cleaved by _________ into monomers.

A

deubiquitinating enzymes

25
Q

How many lysines do ubiquitin contain?

A

7 lysines

26
Q

Ubiquitin is almost always attached to substrate protein through an isopeptide bond between ______ of Ub and the ______ Lys in the substrate.

A

C-terminal Gly; amino group of

27
Q

Minimal signal necessary for proteasome targeting: a chain of ______ linked through _____

A

4 Ub monomers; Lys48

28
Q

mW of traditional chemical-based drugs

A

< 1000Da

29
Q

MW of biopharmaceutical products/ biologics

A

typically in kDa

30
Q

All biopharmaceutical products are protein-based (T/F).

A

False. Not all. Majority (>95%) of biopharmaceuticals are protein products.

31
Q

Definition of convection

A

Collective bulk movement of large mass of particles in a fluid (the flux is fluid- driven/driven by motion of the bulk fluid)

32
Q

2 transport mechanisms for proteins upon SC administration in the ECM

A
  1. Diffusion
  2. Convection
33
Q

Absorption for larger proteins > _____ kDa mostly occur through lymphatic system

A

16-20

34
Q

Smaller proteins < 16-20 kDa, absorption can be via both _________

A

circulatory and lymphatic systems

35
Q

Hypodermis is also known as ____

A

Subcutaneous tissue

36
Q

Rate limiting factors that can cause changes to absorption rates of proteins drugs after SC/IM administration

A
  1. Interstitial fluid transport rate
  2. Lymphatic transport rate
37
Q

Interstitial fluid refer to _____

A

Fluid embedding the ECM

38
Q

Role of FcRn

A

responsible for transport of maternal IgG (1) across placenta to foetus, and (2) from mother’s milk across intestines of newborn babies.

39
Q

FcRn name

A

Neonatal Fc receptor

40
Q

At ______, FcRn binds to Fc domain of IgG or albumin to form FcRn-IgG or FcRn-albumin complex.

A

acidic pH 5-6

41
Q

Charge of protein that allows it to have higher renal filtration

A

Positive charge (since glomerular basement mbm has neg charge)

42
Q

Protein charge that gets reabsorbed by renal tubules

A

Positive charge

43
Q

Factors affecting renal excretion of proteins

A
  1. Charge of protein
  2. MW of protein
  3. Shape & rigidity of protein
  4. Tubular reabsorption of protein
44
Q

2 ways in which proteins can be eliminated

A
  1. Proteolytic degradation (extracellular and intracellular)
  2. Renal (glomerular) filtration (dominates renal excretion of protein drugs)
45
Q

2 types of PEG

A
  1. PEG with free hydroxyl at both ends
  2. methoxylated PEG (mPEG) with hydroxyl at one or both ends methoxylated
46
Q

Substances fused to proteins to incr circulation half-life

A
  1. Fc domain of antibody
  2. Albumin
47
Q

Concern for fusion proteins with Fc domain of antibody

A

Fc domain may trigger unwanted effector functions -> trigger unwanted immune (inflammatory) responses

48
Q

Can a biosimilar biologic be entirely identical to the innovator biologic? Why?

A

No, due to variability of the biological expression system and manufacturing process

49
Q

sialylated glycans almost absent in Mabs produced in ______

A

CHO cells

3152 (18 decks)

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