Principles Of Medicine Flashcards
Evidence for endosymbiotic theory
Mitochondria contain separate DNA with No associated histones
Mitochondria can only be formed from other mitochondria
Mitochondria contain their own protein synthesising complexes with many similarities to prokaryotic machinery
First amino acid of mitochondrial transcript fMET as is the case in bacteria and not MET as in eukaryotes
A number of antibiotics such as streptomycin will also block protein synthesis is mitochondria, but not in cytoplasm of eukaryotes.
Describe the steps of glycolysis including the types of each reaction
Glucose phosphorylated by hexokinase enzyme at carbon 6
- requires ATP investment
- Group transfer
Phosphoglucose Isomerise enzyme converts 5C ring to 4C, creating an extra side branch and molecular symmetry
- isomerization
- glucose 6 phosphate —> fructose 6 phosphate
Fructose-6-phosphate phosphorylated to fructose 1,6 bisphosphate by phosphofructokinase
- Requires ATP investment
- group transfer
Fructose 1,6 bisphosphate hydrolysed by aldolase to 2 3 carbon molecules including glyceraldehyde 3 phosphate
-hydrolysis
Other 3C molecule converted to glyceraldehyde 3 phosphate by TPI
-Isomerization
Inorganic phosphate added to each G3P to form 2x 1,3 bisphophoglycerate
- NAD+ reduced by dehydrogenase enzyme
- Group transfer
1 phosphate group removed by phosphoglycerate kinase enzyme
-ATP generated
Phosphate group moved from position 3->2 by isomerise enzyme (phosphoglycerate mutase)
-isomerization
Water eliminated to form double bond by enolase enzyme
-group removal
ATP generated by removal of final phosphate group by Pyruvate kinase
-group transfers
Describe formation of Lactate from pyruvate under anaerobic conditions
Catalysed by pyruvate dehydrogenase
NADH oxidised
What is the importance of lactate production in anaerobic conditions
Allow NAD+ to be regenerated so that glycolysis can continue as NAD+ is required for dehydration of gkyceraldehyde-3-phosphate
When rate of NADH formation in glycolysis greater than its rate of oxidation in NADH dehydrogenase complex
Describe the role of Creatine phosphate as a buffer
Acts as buffer for storage of ATP
Creatine phosphate + ADP + H+ creatinine + ATP
Catalysed by creatine kinase
Sustain supply first 4s intense exercise
Describe the platelet plug formation
Platelet binds to Von Willebrand factor or to Glpla receptor
ADP and thromboxane released
Thromboxane causes vasoconstriction
Positive feedback mechanism present
Conformational change In GP11b/111a
Opens fibrinogen binding sites
Mechanism of action of aspirin
Inihibits production of thromboxane A2.
Describe formation of a stable haemostatic plug (secondary haemostats)
FVII bind to TF in extravascular environment
Causes activation of fx->Xa and IX->IXa
Cleaves some prothrombin to thrombin
Causes activation of other cofactors which cleave more fX and IXa
Rapid, sustained generation of thrombin
Thrombin catalyses cleavage of fibrinogen to fibrin
Describe the action of protein C
Thrombin binds to thrombomodulin
Causes conformational change of protein C to APc (activates protein C)
Protein C binds and inhibits fVa and VIIIa in presence of protein S
Describe action of antithrombin
Inhibit thrombin and fxa
Potentiated by heparin
Describe the mechanism of action of heparin
Potentiates antithrombin inhibition of thrombin and fXa
IV drip
Mechanism of action of clopidogrel on platelets
Inhibits ADP binding site (P2Y12) on platelet cell membrane.
Lasts 7 days till new platelets produced
What Is the role of calcium ions in the thrombotic cascade
Help bind activated clotting factors to phospholipid surface of platelets
Mechanism of action of Warfarin
Vitamin K antagonist
Reduces synthesis of clotting cofactors
F(2,3,9,10)
Need to monitor
Several days to take effect
Mechanism of action of direct oral amticoagulants (DOACs)
Inhibit thrombin or fXa
Describe fibrinolysis
Plasminogen activated to plasmin by tPA when bound to lysine residues of fibrin
Plasmin catalyse degradation of fibrin clot
Mechanism of action of transexamic acid
Prevents plasminogen binding to lysine residues of fibrin
Prevents fibrinolysis
Describe how prothrombin time (PT) is measured
Blood collected
Sodium citrate added (prevents Ca2+ activating blood clotting)
Sample centrifuged, plasma taken
TF and phospholipid added
Calcium added and timer started
(Can use thromboplastin recombinant instead of phsopholipid and TF)
INR generated- normalised ratio
Pt patient/ Pt average
Describe how activated thromboplastin test is carried out (APTT)
Contact activator such as glass added to phospholipid after addition of sodium citrate and centrifugation
Ca2+ added and time to clot measured
(fXII activated by surface contact)
Describe three causes of bleeding
Reduction in platelet number
Reduction in platelet function
Reduction in coagulation factors
Describe 3 causes of thrombosis
Reduced anticoagulant proteins
Increased levels clotting factors
Increased platelet levels
What is mitochondrial uncoupling?
Any process which disrupts the proton concentration gradient between the intermembrane space and the mitochondrial matrix. Rate of NADH And FADH2 oxidation not linked to rate of ATP synthesis
Action of cyanide on mitochondria
Block cytochrome oxidase complex
Action of Malonate on mitochondria
Competitive inhibitor of succinate dehydrogenase
Slows flow of electrons to Co enzyme Q
Action of Rotenone on mitochondria
Inhibits transfer of electrons from complex 1 to ubiquinone
Action of oligomycin on mitochondria
Block flow of protons in F0F1 ATP synthase complex
Action of dinitrophenol on mitochondria
Introduce micropores in inner membrane
Causes mitochondrial uncoupling
Decreases proton gradient
Describe formation of a granulocyte from a HSC
Multipotent Hemopoeitc stem cell divides and differentiates to form a common myeloid progenitor.
In presence of G-CSF myeloblast formed
Further differentiate to Basophils, neutrophils and eosinophils
Function of neutrophils
Defence against infection
Phagocytosis
Neutrophil migration associated with infection
Function of eosinophils
Defence against parasitic infection
Function of basophils
Involved in regulation of immune responses
Stores of histamine and heparin and proteolytic enzymes
Function of monocytes
Present antigens to lympohoid cells
Migrate to tissues where they develop into tissue macrophages
Function of tissue macrophages
Phagocytic and scavenging function
Storage and release of iron
Describe formation of a natural killer (NK) cell
HSC differentiates to common lymphoid progenitor via mitosis
CLP further differentiates to NK cell
Function of natural killer (NK) cell
Kill tumour cells
Kill virus infected cells
secrete cytotoxic granules