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SoM Flashcards

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1
Q

What is the basic process of cell signalling?

A

Sending cell releases lignads into the extracellular space. The ligands bind to receptors on the target cell, and this binding triggers a chain of chemical messengers within the cell to initiate a change in the activity of the cell.
Sending cell –> Ligands –> Target cell receptor –> Intracellular changes

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2
Q

Synaptic transmission

A

1) AP reaches axon terminal in presynaptic neurone and depolarises the membrane
2) VG Ca2+ channel opens and Ca2+ influxes
3) Ca2+ influx triggers release of neurotransmitter vesicles which diffuse across the synaptic cleft
4) Neurotransmitter binds to receptors on target postsynaptic membrane
5) Activation of receptors on postsynaptic membrane opens/closes VG channels depending on the ions involved

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3
Q

What is the function of Glutamate?

A

Excitatory in the CNS

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4
Q

What is the function of Acetylcholine?

A

Excitatory in skeletal muscle

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5
Q

What is the function of Noradrenaline?

A

Causes vasoconstriction

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6
Q

What are the three domains/protein regions of cell surface receptors?

A

Extracellular ligand binding domain
Hydrophobic domain
intracellular domain (often transmits a signal)

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7
Q

Why can so many different kinds of molecules act as ligands to cell surface receptors? (Including those which are large and/or hydrophilic)

A

The ligand does not need to cross the plasma membrane

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8
Q

GPCR receptor structure?

A

Seven protein segments that cross the membrane

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9
Q

Which nucleotide do all G proteins bind?

A

Guanosine triphosphate (GTP). This is hydrolysed to GDP

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10
Q

When is a G protein ‘on’ or ‘active’

A

When it is attached to GTP

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11
Q

How is a G protein attached to GDP described?

A

‘off’ or ‘inactive’

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12
Q

What is the structure of the G proteins which associate with GPCRs?

A

Heterotrimeric (made up of three subunits)

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13
Q

Function of Gs GPCR?

A

Stimulates adenylate cyclase

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14
Q

Function of Gi GPCR?

A

Inhibits adenylate cyclase

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15
Q

Function of Gq GPCR?

A

Activates phospholipase C

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16
Q

What occurs once a ligand has bound to a Gs receptor?

A

stimulates adenylate cyclase –> ATP converted to cAMP –> cAMP activates Protein Kinase A (PKA) –> PKA phosphorylates protein –> inhibitory Gi receptor switches process off

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17
Q

What is the role of cAMP in cell signalling?

A

Second messenger

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18
Q

What are enzyme-linked receptors?

A

Cell surface receptors whose intracellular domains are associated with an enzyme.
Sometimes, the intracellular domain itself is an enzyme

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19
Q

What are Receptor tyrosine kinases (RTKs)?

A

Class of enzyme linked receptors which transfers phosphate groups to the amino acid tyrosine

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20
Q

What is the process of RTK signalling?

A

Ligands bind to extracellular domains for two nearby RTKs –> neighbouring receptors dimerize –> dimerization activates the tyrosine kinase domains –> receptors phosphorylate tyrosines in each other intracellular domains –> phosphorylated tyrosine transmits the signal to other molecules in the cell

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21
Q

Insulin receptor function?

A

Insulin binds to RTK –> TK activation –> signalling molecules produced –> GLUT4 transporter translocates to cell membrane –> glucose uptake

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22
Q

Intracellular receptors

A

Receptor proteins found on the inside of the cell in cytoplasm or nucleus.

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23
Q

What can bind to intracellular receptors?

A

Usually small, hydrophobic molecules. Ligands must cross the plasma membrane

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24
Q

Nuclear receptor function?

A

Lipid soluble ligands diffuse through plasma membrane –> bind to receptors inside cell –> conformational change –> dimer forms –> Dimer enters nucleus –> dimer binds to recognitions sites on DNA –> triggers/inhibits transcription of specific genes

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25
Families of hormones
AA derivatives Steroids Peptides Proteins Glycoproteins
26
AA derivative eg
Catecholamines - Adrenaline Noradrenaline Thyroid hormones
27
Characteristics of catecholamines
Circulate freely or weakly bound to albumin short half life Bind to GPCR
28
Characteristics of Thyroid hormones
Circulate bound to plasma proteins Long half life Transported through membranes Bind to nuclear receptors
29
Steroids eg
Estrogens Androgens Aldosterone
30
Characteristics of steroid hormones
Circulate bound to plasma proteins Readily diffuse through cell membrane Bind to intracellular receptors Cholesterol is the basis of their structure
31
Characteristics of peptides/proteins/glycoproteins
Usual carved from prohormones as needed Secreted by exocytosis Do not usually bind to plasma proteins Very different structures so effects mediated by several mechanisms
32
Peptides eg
Thyrotropin releasing factor (TRH) Gonadotrophin releasing hormone (GnRH) Adrenocorticotropic hormone (ACTH) ADH Oxytocin Glucagon Somatostatin Vasoactive Intestinal polypeptide (VIP)
33
Protein hormone eg
Insulin Insulin-like growth factors (IGFs) Growth hormone (GH) Prolactin (PRL) Placental Lactogen (PL) Parathyroid hormone (PTH)
34
Paracrine
Secreting cell next to/near to target cell
35
Autocrine
Same cell secretes and receives hormone
36
Paracrine eg
Nitric Oxide (local vasodilator released from endothelial cells)
37
Autocrine eg
Prostaglandins (Inflammatory mediators)
38
Three features of direct communication
Tight junction Desmosome Gap junction
39
Function of Tight Junctions
Gate and Fence mechanisms Prevent passage of molecules Anchor cell to neighbouring cells Not attached to cytoskeleton Stop molecules diffusing around tissue
40
Function of Desmosomes
Join cells together
41
Function of Gap Junctions
Allow communication between cells
42
Juxtacrine
Form of cell signalling between cells which are in direct contact with each other
43
Juxtacrine eg
Gap junctions
44
Paracrine eg
Synapses
45
Gap junctions
Channels/bridges between cells Allow small molecules and ions to pass between cells Small chemical and electrical signals can pass through
46
Are desmosomes attached to cytoskeleton?
Yes
47
Bystander effect
Cells nearby to targeted cells are affected, although they were not hit (eg by radiation in cancer therapy)
48
PCR definition?
Polymerase Chain Reaction
49
What are the uses of PCR for diagnosis?
Identification of pathogens Epigenetic changes Genetic changes Changes in gene expression
50
STR definition?
Short Tandem Repeats (Barcodes for people)
51
What are the uses of STR?
Identification of people
52
Sanger sequencing?
dideoxy chain termination Incorporating dideoxy bases into a chain of new DNA, terminating it, and using the length of the sequence determine the sequence of bases.
53
Next Generation Sequencing (NGS)
massively parallel sequencing - sequencing many short sequences of DNA at the same time to re-sequence DNA where you already know the basic sequence
54
Does mutation = disease?
No
55
Benefits of NGS?
Cheap and powerful
56
How recognise deoxyribonucleic acid?
Hydroxyl group missing on second carbon
57
Where/when does polymerisation occur?
New base must be complementary to base on opposite strand. Phosphate group on the new base form polymerisation reaction with hydroxyl group on carbon 3 of the existing base at the 3' end New base must join at the 3' end
58
Name three motor proteins
Myosin, Kinesin, Dynein
59
What is the structure and function of Kinesis and Dynein
homo-dimers 'head' domain walks along the cytoskeleton (microtubules) central body hydrolyses ATP tail domain interacts with the cargo
60
What process drive intracellular movement of motor proteins along microtubules?
Conformational change driven by ATP hydrolysis
61
Which proteins are involved in muscle movement?
Myosin, actin
62
Ligaments
Fibrous connective tissue that attach bones to bone
63
Tendons
Finbrous connective tissue that connect muscles to bones or other structures
64
Tendon structure
Hierarchical structure Fibroblasts (tenoycytes) Proteoglycan water ECM containing dense collagen fibres grouped into fascicles
65
What are fascicles bound by?
Each fascicle bound by endotendon Group of fascicles bound by epitenon
66
What is the composition of a tendon?
Mostly type 1 collagen Proteoglycan matrix (protein + glycosaminoglycan (GAG) groups) Dermatan sulfate Chondroitin sulfate
67
What is the function of Type 1 collagen?
Connective tissue in skin, tendons, vasculature, organs, and is the main organic component of bone
68
Structure of Tropocollagent
Triple helix Two identical chains (alpha 1) and a different one (alpha 2) Triple helix assembles into a fibril and then into a fibre
69
Structure of bone
30% flexible matrix 70% strengthening inorganic calcium matrix hydroxyapatite
70
Two main types of bone
Cortical/compact Spongy/Trabecular/ Cancellous
71
How is actin arranged in smooth muscle?
Not striated. More actin than myosin Actin inserts into dense bodies and cell membrane
72
Which type of muscle has the most well-developed sarcoplasmic reticulum and transverse tubules? and which has the worst?
Skeletal - best Smooth - worst (no transverse tubules)
73
Which type of muscle contains calmodulin?
Smooth muscle
74
What is calmodulin?
Protein that binds to Ca2+ to activate the enzyme myosin light-chain kinase
75
Where is troponin found in muscles?
In the thin filaments of skeletal and cardiac muscle
76
In smooth muscle, where does Ca2+ enter the cytoplasm from?
Extracellular fluid, sarcoplasmic reticulum and mitochondria
77
In which muscle types does Ca2+ enter cytoplasm from extracellular fluid?
Cardiac and smooth
78
Which muscle types can contract without nerve stimulation?
Cardiac and smooth
79
What happens to skeletal muscle in denervation?
Atrophy
80
What happens to smooth muscle in denervation?
Hypersensitivity to stimulation
81
Where do action potentials originate from in cardiac muscle?
SAN
82
Where do action potientials occur in smooth muscle?
Visceral smooth muscle
83
Which muscle types have gap junctions?
Smooth in Cardiac muscle gap junctions occur as intercalated discs
84
What is the metabolic role of muscle?
Major site of glucose uptake
85
Mechanical role of muscle
Produce body movements and stabilises skeleton
86
Physioloigcal function of muscle
Shivering thermogenesis
87
Structure of muscle
Long parallel bundles of multinucleated cells Fascicles contain parallel myofibrils (contractile elements) Connective tissue (epi, endo and peri-mysium)
88
What is the muscles role in movement
Generates force in tension ONLY this must be converted to movement by anatomy and mechanics
89
What is the contractile element in muscle?
Actomyosin
90
What is the series elastic element in body movement?
tendon, aponeurosis
91
What is the parallel elastic element in body movement?
Various muscle membranes
92
What does a motor unit consist of?
Motor neurone and all the muscles it inervates
93
Pennation angle
Angle between fibres and longitudinal force-generating axis of the muscle Greater pennation angle = less force transmitted to tendon
94
What is the architectural gear ratio (AGR)?
Relates contractile velocity of muscle to contractile velocity of single fibre
95
Low force, high velocity = what AGR?
High AGR
96
What does a low AGR result from?
High force, low velocity
97
What is the job of the sarcoplasmic reticulum?
Specialised smooth ER netwrok which wraps around myofibrils and stores Ca2+
98
What are transverse tubules (T-tubules)?
Sarcolemmal invaginations whihc meet SR in the triads convey the action potential into the myocyte
99
What happens to the zones of the sarcomere as it contracts?
z lines move closer I band becomes smaller A band remains the same width At full contraction thin and thick filaments fully overlap
100
Which proteins are associated with muscle contraction?
Myosin Actin Tropomyosin Troponin
101
What is dystrophin
Large (400kD) cytoskeletal protein localised to inner surface of sarcolemma
102
Which glycoproteins are part of the sarcolemma associated complex?
Laminin, sarcoglycans, dystroglycans
103
What is the effect of defects in the proteins of the sarcolemma associated complex?
many muscular dystrophies depending on which protein is defective. eg Duchenne muscular dystrophy = loss pf dystrophin leads to progressive muscle damage
104
Molecular mechanism of force generation
1 - Ca2+ cross bridge formation between myosin head and actin binding site 2 - dissociation of ADP and Pi, relaxation of high-energy myosin = power stroke 3- binding and hydrolysis of ATP to restore high energy conformation 4- removal of Ca2+ from sarcoplasm, dissociation of the actomyosin complex, muscle relaxation
105
What causes rigor mortis
Absence of ATP, myosin cannot separate from actin, relaxation not possible
106
Roles of Ca2+ in muscle fibres
Release and reuptake from intracellular SR stores controls contraction/relaxation of sarcomeres Uptake into mitochondrial matrix during excitation-metabolism coupling stimulates aerobic ATP production Entry from extracellular space via SOCE limits/delays muscle fatigue
107
Roles of ATP in muscle
Allows dissociation of myosin heads from actin - hydrolysis drives the power stroke Drives Ca2+ reuptake by SR pumps during relaxation Used by Na+/K+ ATPase to re-establish Na+ and K+ gradients after action potential
108
Sources of ATP
Glycolysis/glycogenolysis to lactate oxidation of glucose oxidation of fatty acids
109
Where does energy come from in very short contractions?
Phosphocreatine breakdown Glycogenolysis to lactate
110
How is ATP produced during longer contractions?
Oxidation of pyruvate from glycogenolysis Glucose uptake Glycolysis
111
How is ATP produced during very long contractions?
Oxidation of fatty acid residues from muscle triglyceride Circulating fatty acid from lipolysis of adipose tissue triglyceride
112
make up of the blood
Plasma 55% WBC >1% RBC 45%
113
Types of granular leucocytes?
Neutrophils Eosinophils Basophils
114
Granular leucocytes?
Monocytes Lymphocytes
115

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