Principles Final Condensed Flashcards
apoenzymes vs holoenzymes
with cofactor
without cofactor
Vmax intersection vs Km intersection on Lineweaver Burk Plot
Vmax = Y axis Km = X axis
Low Km means
higher affinity
Does Km or Vmax vary in competitive vs non-competitive inhibition?
Competitive = Km varies Non-competitive = Vmax varies
Enzyme regulation of Hb vs myoglobin
Hb = allosteric control - sigmoidal Myoglobin = Michaelis-Menten
Function of cholesterol
present in cell membranes, component of myelin sheath, precursor molecule for: steroid hormones, Vit D and bile acids
Function of TAGs (triglycerides)
highly concentrated energy store, present in the lipid bilayer
Purines
A and G
Pyramidines
U, T and C
Phosphodiester bonds happen between …
the 3’OH and the 5’triphosphate
what unwinds DNA
helicase
Describe the RNA polymerases in eukaryotes
Pol I, II, III
Pol II synthesises all mRNA
What does RNA polymerase binding require
transcription factors
what is TFIID
general transcription factor required for all Pol II transcribes genes
start codon?
stop codon?
AUG
UAA, UAG, UGA
components of translation
AAs, tRNAs, aminoacyl-tRNA synthetases, protein factors, ATP/GTP, ribosomes and mRNA
Describe initiation in translation
GTP provides the energy
Ribosomal sub-units bind to the 5’ end of mRNA, moves along until the start codon is found
Initiator tRNAs pair to start codon
Large sub-units joins assembly and initiator tRNA is located at the P site
Describe elongation in translation
Elongation factor bring aminoacyl-tRNA to the A site
GTP
Second elongation factor regenerates to pick up the next aminoacyl-tRNA
what does peptidyl transferase catalyse
peptide bond formation between amino acids at the P and A sites
descibe termination in translation
Occurs when the A site o ribosome encounters a stop codon
Finished proteins cleaves of tRNA
what are the 3 tRNA binding sites on ribosomes
Exit
Peptidyl
Aminoacyl
Hexokinase
Phosphofructokinase
Pyruvate kinase
phosphorylates glucose
phosphorylates fructose-6-phosphate
converts phosphoenolpyruvate to pyruvate
negative and positive modulators of phosphofructokinase
\+ve = AMP, fructose-2,6-biphophate -ve = ATP, citrate, H+
aerobic metabolism of pyruvate
enters mitochondria
converted to acetyl-CoA
condenses with 4C compounds to form a 6C comound
6C compound decarboxylates to 2 3C’s - yielding 2CO2
4 oxidation reactions yield NADH+H+ and FADH2
GTP formed
4C compound recreated
where are the enzymes in TCA
all in the matrix apart from succinate dehydrogenase which is in the membrane
Electrons needed in conversion of the NAD and FAD
3 in NAD+ to NADH+H+
1 in FAD to FADH2
phosophoryl transfer potential
free energy change for ATP hydrolysis
Electron transfer potential
measured by redox potential of a compound
standard redox potential
how readily a substance will donate an electron –> -ve values mean reduced from of X has a lower affinity for electrons that hydrogen and vice versa
describe electron transport in the coupling of respiration with ATP synthesis
Respiratory chain - electrons from NADH enter at complex I, electrons from FADH2 enter at complet II, electrons are handed down from higher to lower redox potentials until transferred onto O2 and H2O
Transfer of electronc through respiratory chain is couples with H+ transport from mitochondrial matrix to intermembrane space
3/4 complexes pump H+ (1,2,4)
electrochemical gradient
more protons in inter-membranous space than the matrix making the matrix side more negative and so protons are attracted to the matrix - couples to ATP synthesis
how many ATP does 1 glucose yield
30-32 ATP
what inhibits oxidative phosphorylation
cyanide, azide and CO inhibit the transfer of electrons to O2
aneuploidy
whole missing or extra chromosome
47 XY +21 47 XY +18 47 XXY 47 XY +14 45 X
Down's Syndrome Edward Syndrome Kleinfelter Syndrome Miscariage Turner Syndrome
Sickle cell anaemia
ALzeihmers and Parkinsons
Creutzfeldt-Jacob Disease
Glycogen storage disease
Missense mutation (glu to val)
protein folded before fully synthesised
prions folding goes wrong
enzyme deficiency so cant use glycogen stores
robertsonian translocation
two acrocentric chromosomes stuck end on end - increases risk of trisomy in pregnancy
gonadal mosaicism
causes recurrnece risk for the autosomal dominant conditions even if the parent isnt affected
penetrance
likelihood of having a disease if you ave the gene mutation
autosomal dominant
disease seen in all generations
severity variable males and females equally affected
autosomal recessive
2 faulty copies needed to cause disease
one generation
causes loss of function
x linked
recessive
haemophilia
no male to male transmission
mitochondrial
maternal inheritance
point mutations and deletions occur
mendelian disorders
high penetrance
small environmental contribution
what does DNA methylation lead to
modification of histones which repress transcription
imprinting
the differences in gene expression depending on whether the gene was maternally or paternally inherited
specific chromosomal locations contain imprinting genes
angelmans syndrome
neuro-genetic disorder
chromosome 15
happy demeanour
heteroplasmy
different daughter cells contain different amounts of mutant mitochondria
rough vs smooth ER
R= protein synthesis S= cholesterol and lipid synthesis and detoxification
golgi apparatus
modification and packaging of secretions –> has bound cisternae
microfilaments vs microtubules
7nm composed of Actin
25nm composed of tubulin
Dynein vs kinesin
D = towards centre K = away from centre
site of RNA synthesis
nucleus
types of intracellular junctions
occluding = tight anchoring = desmosomes communicating = gap
cadherin molecules
bind to each other in the extracellular matrix space and to actin of the cytoskeleton
desmosomes vs hemidesmosomes
link submebrane intermediate filaments of adjacent cells
link submebrane intermediate filaments of cells to extracellular matrix through transmembrane proteins
colour of haematoxylin vs eosin
H = purple (basic) E = pink (acidic)
epithelium classification
shape - squamous (flattened), cuboidal an columnar
layers - simple (one), stratified (2+), pseudo-stratified (looks like multiple but is one
exocrine vs endocrine
exo = product secreted to apical end of cell endo = product secreted to basal end of cell ans is transported in the vascular system
diaphysis vs epiphysis
D = outer shell of corticol bone makes up the shaft E = cancellous/trabecular bone occupies the end
blood and lymph connective tissue?
yes
cardiac muscle vs skeletal muscle
C = intercalated discs S = elongated nuclei
connective tissue coat in the CNS vs PNS
C = meninges P = epineurium
types of glia and functions
Astrocytes = support and ion transport
Oligodendrocytes = produce myelin
Microglia = provide immune surveillance
Schwann cell = produce myelin and support axons
3 salivary glands
parotid, sumandibular, sublingual
large intestine, outer longitudinal muscle organisation
teniae coli - 3 strips
bronchus vs bronchioles structure
large diameter and hyaline cartiliage
small, no cartilage, mainly smooth muscle
islets of langerhans
endocrine pancreas
A cells = glucagon
B cells = insulin
D cells = somatostatin
pericytes
connective tissue cells with contractile properties - located in capillaries and venules
3 types of capillary
fenestrated - pores (gut mucosa, kidney, endocrine glands)
continous - (muscle, lung, skin, nerve)
sinusoidal - large gaps (liver, spleen, marrow)
variolation
exposure of an individual to the contents of dried smallpox pustules from an infected patient
what has increased prevalence in HIV caused
reemergence of TB
innate immune response
fast
general
mast cells, NK cells, phagocytes and complement
Adaptive immune response
slow
unique
PRRs:PAMPs vs Antigen:Antigen receptors
innate
adaptive
types of lymphocyte
B cells
T cells
NK cells
types of phagocyte
neutrophils
monocytes
macrophages
dendritic cells
soluble components of the immune response
complement
antibodies - Igs
where are mast cells found and what do they do
reside in tissues and degranulate and release histamine and tryptase
neutrophils produce …. when activated
3 mechanisms of attack
TNF
phagocytosis, release antimicrobial peptides and degredative proteases and generate extracellular traps
where are macrophages found
reside in tissues
monocytes are the precursor
dendritic cells important in
antigen presentation
when activated they mature and go to the secondary lymphoid tissues
helper T cells
CD4+ = produce cytokines, activate CD8+ and recognise peptides on MHC/HLA class II (expressed on dendritic, macrophages and B cells)
cytotoxic T cells
CD8+ = recognise pathogens n MHC/HLA class I (expressed on all nucleated cells), trigger apoptosis and secrete cytokines and pore formign molecules like perforin
examples of cytokines
Interferons
TNF
chemokines
ILs
acute phase response
liver produces acute phase proteins in response to pro-inflammatory cytokines eg IL1, IL6 and TNF
examples of the acute phase proteins = CRP, complement proteins and serum amyloid A
complement pathways
classical
lectin
alternative
MAC is made of
C6-C9 and C5b
T cell antigen receptor vs B cell antigen receptor
T = membrane bound heterodimer (a and b chains) B = membrane bound antibofy (IgM or IgD) - light and heavy chains and disulphide bridges
Exo vs endo toxin
Exo on +ve = mad einside the cell
Endo on -ve = part of cell wall
events in fever
antigen attacks macrophages
releases cytokines
travel to anterior hypothalamus of the brain
stimulates production of PGE
reset bodys thermal temperature
body perceives cold and so shiver to conserve heat
FEVER
antibiotic in anaerobes
antibiotic for staph aureus
antibiotic for coliforms
metronidazole
flucloxacillin
gentamicin
cell wall antibiotics
penicillin (beta lactam), cephalosporins (ceftriaxone), glycopeptides - only effectove on gram +ve cell walls (vancomycin )
all bactericidal
protein synthesis antibiotics
macrolides (thromycin’s), textracyclines (doxycycline) and aminoglysides (gentamicin)
all bacteriostatic appart from gentamicin
bacterial DNA antibodies
metronidazole, trimethopim and fluouroquinolones
what are the neutralising antibodies of viruses
IgM and IgG
non lethal cell injury
hydropic change
fatty change
membrane shedding
meatbolic disorders inheritance
autosomal recessive
phenylketonuria
Guthrie test - due to the accumulation of phenylalanine caused by a deficiency in enzyme converts phenylalanine to tyrosine
surface adhesion molcules
C5a
Leukotriene B2
TNF
endothelial cell expression of adhesion molecules increased by
IL1, endotoxins and TNF
5-HT (serotonin) in high concentration where
platelets
cells of chronic inflammation
plasma cells, lymphocytes and macrophages
irreversible damage in inflammation
severe damage to the cell membrane and mitochondria
leakage of enzymes
nuclear changes eg ATP changes, cell membrane damage
labile cells
stable cells
Gi tract and bone marrow
hepatocytes and endothelium
p53 activated by
arrests cycle at
cell stress
G1/S or G2/M
T1 diabetes vs T2 diabetes
T1 = insulin dependent T2 = non-insulin dependent
orthoteric vs allosteric sites
competitive (same)
non-competitive (different)
Henderson-Hasselbach equation
pH -pKa = log(A-/AH)
Vd in IV setting
Vd= dose/plasma concentration
parasympathetic cranial nerves
3,7,9,10
what does noradrenaline activate
G protein coupled receptors - adrenoceptors
muscarinic ACh receptors vs nicotinic ACh receptors
M = G protei coupled receptors where they are all seperate parts N = ligand gated channel essentially with alpha, beta, gamma, delta and epsilon units
M1
M2
M3
Gq - stimulates phospholipase C - incr stomach acid secretion
Gi - inhibits adenylyl cyclase, opens K channels - decrease HR
Gq - stimulates phospholipase C - incr saliva secretion and bronchoconstriction
MAO vs COMT
MAO = U1 NA metabolism COMT = U2 NA metabolism
B1
B2
A1
A2
Gs - stimulates adenylyl cyclase - incr HR and force
Gs - stimulates adenylyl cyclase - relax brocnhial and vascular smooth muscle
Gq - stimulates phospholipase C - contraction of vascular smooth muscle
Gi - inhibits adenylyl cyclase - inhibits NA release
amphetamine
U1 substrate
inhibits MAO
displaces NA into the cytoplasm so incr ADR stimulation
1st order kinetics vs zero order kinetics
rate of elimination directly proportional to the drug concentration (T1/2 = 0.69/Kel)
initially eliminated at constant rate and then changes to first order pattern
rate of elimination =
clearance x plamsa concentration
Cpss and Css
maintenance dose rate/clearance
is reached after approximately 5 half lives
Phase 1 drug metabolism
right side of liver
oxidation, reduction and hydrolysis
makes drug more polar
Phase 2 drug metabolism
left side of liver
conjugation
adds endogenous compounds to increase polarity
glomerular filtration
unbound only
occurs freely for most drugs
organic anion transporter
organic cation transporter
handles acidic drugs - penicillins, uric acid, furesimide, thaizides (gout)
handles basic drugs - morphine
active tubular secretions
what can active tublar secretions do
concentrate drugs in tubular fluid against the concentration gradient
factors affecting reabsorption
lipid solubility
polarity
urinary flow rate
urinary pH (basic = incr excretion of acid, acidic = increase excretion of base)
feedback of Na vs K channels in an AP
Na = +ve feedback K = -ve feedback
what is the state of the Na channels in the absolute refractory period
inactive
oligodendrocytes
astrocytes
microglia
priduce myelinated cells in the CNS
star shaped, support homeostasis and maintain BBB
immune surveillance, mrcophages of the CNS
what forms the glycocalyx layer
glycoproteins and glycolipids - carbohydrates
cell adhesion molecules
cadherin = hold cells in tissues together integrins = span membrane acting as a link between extra and intracellular environment
what is osmolatiry nd how to caluclate
concetration of osmotically active particles in a solution
osmoles/litre
tonicity meaning
effect a solution has on a cell volume
Na/K ATPase what goes in and out
3Na in
2K out
membrane is more permable to Na or K
K
nernst equation
Eion = 61 log ([ion]0/[ion]i)
Goldman-Hodgkin-Katz
each ion in turn and its relative permaeability
calculates overall membrane potential
hormones controlling glucose:
absorptive and post absorptive state
emergency
starvation
insulin and glucagon
adrenaline
cortisol and growth hormone
insulin favours anabolism or catabolism
anabolism
hormone of the fed state
where does the growth hormone come from
anterior lobe of the pituitary
methods of heat gain
metabolic heat
radiation
convection
methods of heat loss
convection
conduction
radiation
evaporation
heat regulator in the brain
hypothalamus
