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Blake_Biochemistry Test II > Blake_Biochem_18_Transport through membranes I > Flashcards

Blake_Biochem_18_Transport through membranes I Flashcards

1
Q

Types of integral membrane proteins (4)

A

Monotopic

Bitopic type I (N term out)

Bitopic type II (C term out)

Polytopic

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2
Q

Types of associated membrane proteins (3)

A

Protein associated

Acyl anchored

Phospholipid associated

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3
Q

Transport proteins are usually what type of membrane proteins?

A

Polytopic, transmembrane, integral membrane proteins

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4
Q

Transport properties of the plasma membrane: (4)

A

*Semi-permeable

*Permeable to : lipophilic

* Impermeable to : hydrophilic molecules

*require transport mechanisms to move large or polar molecules

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5
Q

What determines the ionic composition of the cell?

A

activity and protein levels of specific transporters

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6
Q

How do cells govern the biochemical/metabolic characteristics of their specific needs? Why is this significant?

A

Expression of specific transporters cells can only execute those reactions whose substrates can be taken up

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7
Q

How can cells use transporters to regulate metabolism?

A

Alteration in expression levels of transport proteins

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8
Q

Extra/Intracellular concentration of Na+ Fold-Difference

A

Extra 145 mM

Intra 12 mM

12

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9
Q

Extra/Intracellular concentration of K+ Fold-Difference

A

Extra 4 mM

Intra 155 mM

0.026 fold difference

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10
Q

Extra/Intracellular concentration of Ca2+ Fold-difference

A

Extra 1 mM

Intra 0.0001 mM

>10,000 fold difference

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11
Q

Extra/Intracellular concentration of Cl- Fold-Difference

A

Extra 120 mM

Intra 4 mM

30 fold difference

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12
Q

Energy independent movement of molecules down a gradient is called ___________ occurs in two ways:

A

Passive Transport

Simple diffusion, Facilitated diffusion

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13
Q

What determines the rated of simple diffusion accross a membrane

A

The concentration gradient; Higher the difference, faster the diffusion.

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14
Q

Unequal distribution of molecules is associated with ___________

How doe cells set up an ion gradient across the membrane?

A
  • Free energy
  • Energy is utilized by ATP driven membran proteins and then stored as free energy for the gradient.
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15
Q

Gibbs free energy for an uncharged molecule:

A

DeltaG=2.303RTlog10[Co/Ci]

R = 8.3144598 J/mol*K

T = temp in Kelvin (273+ºC)

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16
Q

Gibbs free engergy for a charged molecule

A

DeltaG=2.303RTlog10[Co/Ci] +ZFDeltaV

Z = Electrical Charge

F= Faraday’s Constant (9.648 70 x 104)

Delta V= membrane potential

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17
Q

How are concentration and membrane potential related to Free Energy?

A

both are directly proportional to free energy

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18
Q

Two Types of ATP utilizing proteins:

A

P-type ATPases

ATP Binding Cassete Transporters

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19
Q

4 kinds of P-Type ATPases:

A
  • Na+, K+-ATPase
  • Plasma Membrane Ca2+-ATPase (PMCA)
  • Sarcoplasmic Reticulum Ca2+-ATPase (SERCA)
  • H+, K+-ATPase
20
Q

Why are antioxidants important for brain health?

How are the colorful, anti-oxidants in fruits and vegitables broadly categorized?

A
  • The rapid metabolic rate in the brain (20% of caloric intake), creates considerable amount of oxidative stress.
  • Flavanoids*

*Flavonoids are a group of plant metabolites thought to provide health benefits through cell signalling pathways and antioxidant effects. These molecules are found in a variety of fruits and vegetables.Flavonoids are polyphenolic molecules containing 15 carbon atoms and are soluble in water.

21
Q

How were ATP binding cassette transporters discovered?

A

Studying multi-drug resistance in Tumor cells

22
Q

How does ATP change the conformation of P-type ATPases?

A

Phosphate is cleaved from ATP and covalently bonds with protein => energy is released => conformation is changed.

23
Q

How many types of P-type ATPases are present in the human genome?

A

70

24
Q

Which residue(s) does the cleaved phosphate from ATP covalently bond to on a P-type ATPase?

A

Aspartate (D)

25
Q

Steps in conformation of P-type ATPases:

A
  1. ATP breaks into ADP and phosphate
  2. Transporter forms a covalent bond with the phosphate to form an enzyme-phosphate intermediate
  3. Phosphorylation occurs on a conserved aspartate residue
  4. Transporter undergoes a drastic convormational change that facilitates the transport of ions accross the membrane
26
Q

What does it mean that P-type ATPases use a “fundimental mechanism of action?”

A

there is a single action that is only caused by ATP hydrolysis

27
Q

General facts about Sodium Pump (6)

[purpose, ratio, outcomes(3), loccation]

A
  1. Establishes Na+/K+ gradient
  2. Stoichiometry: 3 Na+ out/2 K+ in for 1 ATP
  3. Makes neurons and muscle cells electircally ecitable
  4. controls cell volume
  5. drives active transport of sugars and amino acids
  6. 20-40% of brain ATP is used by Na+pump
28
Q

Inhibitors of Na+ pump (6)

A
  1. Plant steroids
  2. Inhibid DEphosphorylation of E2P
  3. Eg: digitoxigenin and oubain
  4. called cardiotonic steroids
  5. digitalis contains mixture of cardiotonic steriods
  6. used in treatment of congestive heart failure
29
Q

Two common Cardiac glycosides

A

Ouabain

Digitoxigenin

30
Q

What is the effect of action for cardiac glycosides? (6)

A
  1. Inhibit Na+/K+ ATPase activity
  2. Increase levels of Na+ in cell
  3. Reduce activity of Na+/Ca2+ antiporter
  4. increase in Ca2+ in cell
  5. Elevated Ca2+ increases the contractile force of cardiac muscle
  6. Used in treatment of congestive heart failure
31
Q

Two kinds of Calcium Pumps

A

Plasma membrane (PMCA)

Sarco-endoplasmic reticulum (SERCA)

32
Q

PMCA (3)

A

Plasma Membrane Calcium ATPase

  • 10 transmembrane domains
  • size: 140 kDa
  • Stimulated by calcium binding protein calmodulin (CaM)
33
Q

Sites/Domains of PMCA (3)

A
  • Phosphorylation domain
  • CaM Binding Domain
  • ATP Binding Site
34
Q

How does the CaM binding domain regulate PMCA?

A
  • PMCA is autoinhibited by its own CaM binding domain
  • CaM binding domain blocks Phoshphorylation and ATP-binding sites until active CaM binds, at which point the CaM binding domain dissociates from the active site and “swings away”. (like a “ball and “ chain” plug but over active site).
35
Q

CaM and PMCA

A

Calmodulin stimulates PMCA into active state

36
Q

SERCA (4)

A

Sarco-endoplasmic Reticulum Caclium ATPase

  • 110kDa
  • Transoirts Calcium from cytosol to SR
  • 80% of SR membrane proteins
  • Relaxes contracted muscle
37
Q
  • Where does phosphate bind to SERCA?
  • How does the conformation of SERCA change when phosphate binds to it?
  • How are the Calcium-Binding sites of SERCA affected by bound phosphate?
A
  • Asp 351
  • N and P domains close around the phosphoaspartate analog
  • Calcium-binding domains are disrupted
38
Q

ABC Transporters stands for _____

A

ATP Binding Cassette Transporters

39
Q

How many ABC transporter genes are on the human Genome?

A

150

40
Q

How were ABC transporters discovered?

How do they generally work?

how else are they identified? (2)

A

by studying drug resistance in tumor cells

“put drug in and it pushes it back out”

Multi-drug resistance protein/ P glycoprotein

41
Q

What are the 4 parts of MDR from N to C?

A

N-Membrane spaning domain-ATPbinding Cassette-Membrane spanning domain - ATPbinding Cassette-C

42
Q

Mechanism of Action of ABC Transporters

A
  1. No substrate or ATP bound: channel faces in
  2. Binding of substrate causes conformational change in ATP binding cassettes
  3. Affinity for ATP increases SO ATP Binds
  4. Binding of ATP causes conformation of ATP binding Cassettes to changse THEREFORE membrane spaning domains are reoriented
  5. Substrate is expelled on extracellular side
  6. ATP Hydrolysis resets transporter to Step 1
43
Q

Secondary Transporters

A
  • Not directly driven by ATP
  • Thermodynamically unfavorable flow of one species against a gradient coupled to the favorable flow of another species down a gradient.
44
Q

Three types of Secondary Transporters

A
  • Antiporters - oposite direction (eg: NCX)
  • Symporters - same direction (eg: lactose permease)
  • Uniporter - depends on concentration (eg: Mitochondrial Calcium Transporter)
45
Q

Lactose Permease

A
  • a symporter
  • Uses the proton gradient generated by oxidation of fuel molecules to drive lactose and other sugars against the concentration gradient
46
Q

Mechanism of Action for Lactose Permease

A

H+ out; Lactose out

H+ in; Lactose in

Blake_Biochemistry Test II (11 decks)

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