Lecture 15: Signal Transduction/Lecture 16: Carbohydrates Flashcards Preview

Biochemistry 2300 > Lecture 15: Signal Transduction/Lecture 16: Carbohydrates > Flashcards

Flashcards in Lecture 15: Signal Transduction/Lecture 16: Carbohydrates Deck (44):
1

Classifications of cell signalling (3)

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

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Ligands

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

3

Agonist

Ligand that initiates a biological response

4

Antagonist

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

5

Kd

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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Second messengers

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

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Second messenger: cAMP

Derived from ATP by activation of adenylate cyclase
Removed by phosphodiesterase

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Second messenger: phospholipids

Hydrolysis gives variety of second messengers
Ie. DAG, IP3

9

Second messenger: Ca

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

10

Protein phosphorylation

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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G-proteins

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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Heterotrimeric G-proteins

Directly activated by GPCRs

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Monomeric G-proteins

Involved in signal transduction, small GTPases, Ras family

14

GPCR

7 transmembrane domains as alpha helices
Ligand binding to the outside causes conformational change that activates G-protein on the inside

15

GPCR activation of Protein Kinase 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

16

Receptor Tyrosine Kinase

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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Ras

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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GlyH12

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

19

Oncogenes

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)

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Carbohydrates

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

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Glycosidic bonds

Attached carbohydrate monomers to form oligo/polysaccharides
Between hydroxyl groups to cause loss of H2O

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Monosaccharides

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

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Aldoses

Monosaccharide that contained an aldehyde

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Ketoses

Monosaccharide that contains a ketone

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Furanose

Monosaccharide ring with 5 carbons and one oxygen

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Pyranose

Monosaccharide ring with 6 carbons and one oxygen

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Glyceraldehyde

Simplest sugar
One chiral centre
D and L form are enantiomers

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Carbohydrate stereochemistry

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

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Epimers

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

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Anomeric carbon

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

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Haworth projection

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

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Linear carbohydrate chains

1 to 4 linkages using glycosidic bonds

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Branched carbohydrate chains

1 to 6 linkages using glycosidic bonds
Carbohydrates with multiple hydroxyl groups

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Aldohexoses

Glucose, galactose, mannose
Usually form 6-membered pyranose rings

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Glycogen

Main storage form of glucose in mammals (liver, muscle)
alpha 1,4 linkages with alpha 1,5 branches every 12 residues

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Starch

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

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Cellulose

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

38

Glycoproteins

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

N-linked

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

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O-linked

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

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Proteoglycans

Consist of large glycosaminoglycans attached to peptides
Provide spongy hydrates coat to mammalian cells

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Chitin

Makes exoskeleton of insects and crustaceans

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ABO blood group

Sugars attached to cell surface protein or lipid

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Lipopolysaccharides

Provide outer membrane barrier for Gram-negative bacteria