Lecture 15: Signal Transduction/Lecture 16: Carbohydrates Flashcards

1
Q

Classifications of cell signalling (3)

A
  1. Nature and origin of extracellular signal
  2. Type of receptor involved
  3. Physiological system
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2
Q

Ligands

A

Extracellular messenger molecules, bind to specific receptors, mainly bind membrane receptor proteins

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3
Q

Agonist

A

Ligand that initiates a biological response

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4
Q

Antagonist

A

Binds to receptor and causes no response, prevents other signalling molecules to bind and cause response

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5
Q

Kd

A

Dissociation constant, concentration of the ligand when the receptor is half-saturated, low values for Kd indicate high affinity
Kd= [R][L]/[R x L]

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6
Q

Second messengers

A

Propagate signals in cell, transient, kept at low intracellular levels until needed then are generated from abundant cellular precursors

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7
Q

Second messenger: cAMP

A

Derived from ATP by activation of adenylate cyclase

Removed by phosphodiesterase

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8
Q

Second messenger: phospholipids

A

Hydrolysis gives variety of second messengers

Ie. DAG, IP3

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9
Q

Second messenger: Ca

A

Cytosolic free Ca rises 100x from extracellular. and organelles sourced with ion activation
Skeletal contraction

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10
Q

Protein phosphorylation

A

Protein kinases transer PO4 from ATP to substrate proteins at Ser, Thr, and Tyr
Conserved catalytic and regulatory domains
Reversed by protein phosphatases
May modify activity or provide docking sites for signalling proteins
Target is usually protein kinases to amplify signal
Slower than Ca signalling

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11
Q

G-proteins

A

When bound to GTP, bind and activate downstream proteins
Intrinsic GTPase activity causes them to act as timers
1. Heterotrimeric G-proteins
2. Monomeric G-protiens

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12
Q

Heterotrimeric G-proteins

A

Directly activated by GPCRs

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13
Q

Monomeric G-proteins

A

Involved in signal transduction, small GTPases, Ras family

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14
Q

GPCR

A

7 transmembrane domains as alpha helices

Ligand binding to the outside causes conformational change that activates G-protein on the inside

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15
Q

GPCR activation of Protein Kinase A

A
  1. Hormone binds to GCPR
  2. Activation of Gs protein, alpha subunit dissociates and activated adenylyl cyclase
  3. Adenylyl cyclase makes cAMP, which acts on the regulatory subunits on PKA
  4. PKA activated when regulatory subunits interact with cAMP and dissociate from catalytic subunits
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16
Q

Receptor Tyrosine Kinase

A

Single transmembrane domain, respond to ligand binding by dimerizing, activates internal kinase domain and auto/cross-phosphorylate Tyr resides
Tyr (phosphorylated) act as docking sites for other proteins, uses modular protein domains to recruit signalling molecules and cause downstream responses

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17
Q

Ras

A

Monomeric G protein, involved in many RTK signalling pathways leading to cell proliferation
Interacts with multiple downstream signalling proteins when bound to GTP
Mutations near active site impair its GTPase activity leaving it always on

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18
Q

GlyH12

A

Active site of Ras
Mutations near site leave protein constitutively active
Ras mutations are present in 30% of humans cancers

19
Q

Oncogenes

A

Cancer causing genes
Accelerates cell growth, reduced apoptosis, mitosis before DNA damage corrected, reduced/abnormal DNA repair, abnormal gene expression
(Also caused by loss of function of tumour suppressor genes)

20
Q

Carbohydrates

A

Hydrates of carbon, general formula (CH2O)n, where n is greater than/equal to 3
Major roles: energy from diet, structural support, molecular recognition
Monosaccharide or polymers
Linear or branched

21
Q

Glycosidic bonds

A

Attached carbohydrate monomers to form oligo/polysaccharides

Between hydroxyl groups to cause loss of H2O

22
Q

Monosaccharides

A

Classified by:

  1. Nature of carbonyl group: aldoses, ketoses
  2. Number of carbons (numbered from carbonyl end)
  3. Ring size
  4. Stereochemistry
23
Q

Aldoses

A

Monosaccharide that contained an aldehyde

24
Q

Ketoses

A

Monosaccharide that contains a ketone

25
Q

Furanose

A

Monosaccharide ring with 5 carbons and one oxygen

26
Q

Pyranose

A

Monosaccharide ring with 6 carbons and one oxygen

27
Q

Glyceraldehyde

A

Simplest sugar
One chiral centre
D and L form are enantiomers

28
Q

Carbohydrate stereochemistry

A

Chiral centres
D/L destination reserved for chiral carbon furthest from carbonyl group
Most in D configuration (hydroxyl to the right)

29
Q

Epimers

A

Two monosaccharide isomers with different orientation about any one carbon except anomeric carbon

30
Q

Anomeric carbon

A

Carbon farthest from carbonyl group in monosaccharide, D/L configuration
Attack by OH group produces alpha and beta configurations
If OH group is unattached, alpha and beta forms can freely interconvert with beta predominating

31
Q

Haworth projection

A

Fischer projection tilted 90 degrees right, anomeric hydroxyl group below (alpha) or above (beta) the plane of the ring

32
Q

Linear carbohydrate chains

A

1 to 4 linkages using glycosidic bonds

33
Q

Branched carbohydrate chains

A

1 to 6 linkages using glycosidic bonds

Carbohydrates with multiple hydroxyl groups

34
Q

Aldohexoses

A

Glucose, galactose, mannose

Usually form 6-membered pyranose rings

35
Q

Glycogen

A

Main storage form of glucose in mammals (liver, muscle)

alpha 1,4 linkages with alpha 1,5 branches every 12 residues

36
Q

Starch

A

Energy storage in plants

Consists of glucose in alpha 1,4 linear (amylose) or alpha 1,6 branched (amylopectin) chains

37
Q

Cellulose

A

Provides structural rigidity to plant cell walls
Undigestible beta 1,4 linked glucose chains
Heavily hydrogen bonded into fibres

38
Q

Glycoproteins

A

Attachment of oligosaccharides to proteins: provides variety in molecular recognition
N-linked or O-linked
Carbohydrate portion of glycoproteins face exterior/lumenal membrane side
Functions in protein targeting and stability

39
Q

N-linked

A

to Asn
Added during translation into ER as preformed 14-mer from dolichol
Trimmed and rebuilt to prices in the ER

40
Q

O-linked

A

to Ser, Thr
Added one until at a time in the Golgi
Can be quite large

41
Q

Proteoglycans

A

Consist of large glycosaminoglycans attached to peptides

Provide spongy hydrates coat to mammalian cells

42
Q

Chitin

A

Makes exoskeleton of insects and crustaceans

43
Q

ABO blood group

A

Sugars attached to cell surface protein or lipid

44
Q

Lipopolysaccharides

A

Provide outer membrane barrier for Gram-negative bacteria