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Foundation Block > SoM > Flashcards

SoM Flashcards

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
Q

Families of hormones

A

AA derivatives
Steroids
Peptides
Proteins
Glycoproteins

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26
Q

AA derivative eg

A

Catecholamines -
Adrenaline
Noradrenaline

Thyroid hormones

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27
Q

Characteristics of catecholamines

A

Circulate freely or weakly bound to albumin
short half life
Bind to GPCR

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28
Q

Characteristics of Thyroid hormones

A

Circulate bound to plasma proteins
Long half life
Transported through membranes
Bind to nuclear receptors

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29
Q

Steroids eg

A

Estrogens
Androgens
Aldosterone

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30
Q

Characteristics of steroid hormones

A

Circulate bound to plasma proteins
Readily diffuse through cell membrane
Bind to intracellular receptors
Cholesterol is the basis of their structure

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31
Q

Characteristics of peptides/proteins/glycoproteins

A

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

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32
Q

Peptides eg

A

Thyrotropin releasing factor (TRH)
Gonadotrophin releasing hormone (GnRH)
Adrenocorticotropic hormone (ACTH)
ADH
Oxytocin
Glucagon
Somatostatin
Vasoactive Intestinal polypeptide (VIP)

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33
Q

Protein hormone eg

A

Insulin
Insulin-like growth factors (IGFs)
Growth hormone (GH)
Prolactin (PRL)
Placental Lactogen (PL)
Parathyroid hormone (PTH)

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34
Q

Paracrine

A

Secreting cell next to/near to target cell

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35
Q

Autocrine

A

Same cell secretes and receives hormone

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36
Q

Paracrine eg

A

Nitric Oxide
(local vasodilator released from endothelial cells)

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37
Q

Autocrine eg

A

Prostaglandins
(Inflammatory mediators)

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38
Q

Three features of direct communication

A

Tight junction
Desmosome
Gap junction

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39
Q

Function of Tight Junctions

A

Gate and Fence mechanisms
Prevent passage of molecules
Anchor cell to neighbouring cells
Not attached to cytoskeleton
Stop molecules diffusing around tissue

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40
Q

Function of Desmosomes

A

Join cells together

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41
Q

Function of Gap Junctions

A

Allow communication between cells

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42
Q

Juxtacrine

A

Form of cell signalling between cells which are in direct contact with each other

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43
Q

Juxtacrine eg

A

Gap junctions

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44
Q

Paracrine eg

A

Synapses

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45
Q

Gap junctions

A

Channels/bridges between cells
Allow small molecules and ions to pass between cells
Small chemical and electrical signals can pass through

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46
Q

Are desmosomes attached to cytoskeleton?

A

Yes

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47
Q

Bystander effect

A

Cells nearby to targeted cells are affected, although they were not hit (eg by radiation in cancer therapy)

48
Q

PCR definition?

A

Polymerase Chain Reaction

49
Q

What are the uses of PCR for diagnosis?

A

Identification of pathogens
Epigenetic changes
Genetic changes
Changes in gene expression

50
Q

STR definition?

A

Short Tandem Repeats (Barcodes for people)

51
Q

What are the uses of STR?

A

Identification of people

52
Q

Sanger sequencing?

A

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
Q

Next Generation Sequencing (NGS)

A

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
Q

Does mutation = disease?

A

No

55
Q

Benefits of NGS?

A

Cheap and powerful

56
Q

How recognise deoxyribonucleic acid?

A

Hydroxyl group missing on second carbon

57
Q

Where/when does polymerisation occur?

A

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
Q

Name three motor proteins

A

Myosin, Kinesin, Dynein

59
Q

What is the structure and function of Kinesis and Dynein

A

homo-dimers
‘head’ domain walks along the cytoskeleton (microtubules)
central body hydrolyses ATP
tail domain interacts with the cargo

60
Q

What process drive intracellular movement of motor proteins along microtubules?

A

Conformational change driven by ATP hydrolysis

61
Q

Which proteins are involved in muscle movement?

A

Myosin, actin

62
Q

Ligaments

A

Fibrous connective tissue that attach bones to bone

63
Q

Tendons

A

Finbrous connective tissue that connect muscles to bones or other structures

64
Q

Tendon structure

A

Hierarchical structure
Fibroblasts (tenoycytes)
Proteoglycan water ECM containing dense collagen fibres grouped into fascicles

65
Q

What are fascicles bound by?

A

Each fascicle bound by endotendon
Group of fascicles bound by epitenon

66
Q

What is the composition of a tendon?

A

Mostly type 1 collagen
Proteoglycan matrix (protein + glycosaminoglycan (GAG) groups)
Dermatan sulfate
Chondroitin sulfate

67
Q

What is the function of Type 1 collagen?

A

Connective tissue in skin, tendons, vasculature, organs, and is the main organic component of bone

68
Q

Structure of Tropocollagent

A

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
Q

Structure of bone

A

30% flexible matrix
70% strengthening inorganic calcium matrix hydroxyapatite

70
Q

Two main types of bone

A

Cortical/compact
Spongy/Trabecular/
Cancellous

71
Q

How is actin arranged in smooth muscle?

A

Not striated.
More actin than myosin
Actin inserts into dense bodies and cell membrane

72
Q

Which type of muscle has the most well-developed sarcoplasmic reticulum and transverse tubules? and which has the worst?

A

Skeletal - best
Smooth - worst (no transverse tubules)

73
Q

Which type of muscle contains calmodulin?

A

Smooth muscle

74
Q

What is calmodulin?

A

Protein that binds to Ca2+ to activate the enzyme myosin light-chain kinase

75
Q

Where is troponin found in muscles?

A

In the thin filaments of skeletal and cardiac muscle

76
Q

In smooth muscle, where does Ca2+ enter the cytoplasm from?

A

Extracellular fluid, sarcoplasmic reticulum and mitochondria

77
Q

In which muscle types does Ca2+ enter cytoplasm from extracellular fluid?

A

Cardiac and smooth

78
Q

Which muscle types can contract without nerve stimulation?

A

Cardiac and smooth

79
Q

What happens to skeletal muscle in denervation?

A

Atrophy

80
Q

What happens to smooth muscle in denervation?

A

Hypersensitivity to stimulation

81
Q

Where do action potentials originate from in cardiac muscle?

A

SAN

82
Q

Where do action potientials occur in smooth muscle?

A

Visceral smooth muscle

83
Q

Which muscle types have gap junctions?

A

Smooth
in Cardiac muscle gap junctions occur as intercalated discs

84
Q

What is the metabolic role of muscle?

A

Major site of glucose uptake

85
Q

Mechanical role of muscle

A

Produce body movements and stabilises skeleton

86
Q

Physioloigcal function of muscle

A

Shivering thermogenesis

87
Q

Structure of muscle

A

Long parallel bundles of multinucleated cells
Fascicles contain parallel myofibrils (contractile elements)
Connective tissue (epi, endo and peri-mysium)

88
Q

What is the muscles role in movement

A

Generates force in tension ONLY
this must be converted to movement by anatomy and mechanics

89
Q

What is the contractile element in muscle?

A

Actomyosin

90
Q

What is the series elastic element in body movement?

A

tendon, aponeurosis

91
Q

What is the parallel elastic element in body movement?

A

Various muscle membranes

92
Q

What does a motor unit consist of?

A

Motor neurone and all the muscles it inervates

93
Q

Pennation angle

A

Angle between fibres and longitudinal force-generating axis of the muscle
Greater pennation angle = less force transmitted to tendon

94
Q

What is the architectural gear ratio (AGR)?

A

Relates contractile velocity of muscle to contractile velocity of single fibre

95
Q

Low force, high velocity = what AGR?

A

High AGR

96
Q

What does a low AGR result from?

A

High force, low velocity

97
Q

What is the job of the sarcoplasmic reticulum?

A

Specialised smooth ER netwrok which wraps around myofibrils and stores Ca2+

98
Q

What are transverse tubules (T-tubules)?

A

Sarcolemmal invaginations whihc meet SR in the triads
convey the action potential into the myocyte

99
Q

What happens to the zones of the sarcomere as it contracts?

A

z lines move closer
I band becomes smaller
A band remains the same width
At full contraction thin and thick filaments fully overlap

100
Q

Which proteins are associated with muscle contraction?

A

Myosin
Actin
Tropomyosin
Troponin

101
Q

What is dystrophin

A

Large (400kD) cytoskeletal protein localised to inner surface of sarcolemma

102
Q

Which glycoproteins are part of the sarcolemma associated complex?

A

Laminin, sarcoglycans, dystroglycans

103
Q

What is the effect of defects in the proteins of the sarcolemma associated complex?

A

many muscular dystrophies depending on which protein is defective.
eg Duchenne muscular dystrophy = loss pf dystrophin leads to progressive muscle damage

104
Q

Molecular mechanism of force generation

A

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
Q

What causes rigor mortis

A

Absence of ATP, myosin cannot separate from actin, relaxation not possible

106
Q

Roles of Ca2+ in muscle fibres

A

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
Q

Roles of ATP in muscle

A

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
Q

Sources of ATP

A

Glycolysis/glycogenolysis to lactate
oxidation of glucose
oxidation of fatty acids

109
Q

Where does energy come from in very short contractions?

A

Phosphocreatine breakdown
Glycogenolysis to lactate

110
Q

How is ATP produced during longer contractions?

A

Oxidation of pyruvate from glycogenolysis
Glucose uptake
Glycolysis

111
Q

How is ATP produced during very long contractions?

A

Oxidation of fatty acid residues from muscle triglyceride
Circulating fatty acid from lipolysis of adipose tissue triglyceride

112
Q

make up of the blood

A

Plasma 55%
WBC >1%
RBC 45%

113
Q

Types of granular leucocytes?

A

Neutrophils
Eosinophils
Basophils

114
Q

Granular leucocytes?

A

Monocytes
Lymphocytes

115
Q
A

Foundation Block (2 decks)

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