quiz 2.1 O2 and CO2 Flashcards
exchange of gases between external and internal environment
ventilation
exchange of gas between tissue and blood
internal respi
how does blood and tissue exchange gases
diffusion
conserved amino acid in both hb and mb
his F8 and E7
phe CD1 and leu F4
gly B6
these amino acids in hb and mb are for heme contact (hydrophobic poket)
phe CD1 and leu F4
this amino acid in hb and mb allows the close approach of helices B and E
gly B6
compact globular protein with ____ amino acids folded in ____ right handed alpha helices A to H
myoglobin
153
9
approximately 75% of Hb is in the form of an
alpha helix
Hb has __ heme groups and therefore ___ oxygen binding sites
4
4
characteristics of Hb
64 kd
heterotetramer with 2 pairs of globin polypeptde chains
structure of HbA
alpha2/beta2
structure of Hb Gower1
zeta2/epsilon2
structure of Hb Portland
zeta2/gamma2
the prosthetic group of Hb and Mb located in the hydrophobic pocket
heme
structure of heme
protoporphyrin ring with bound iron
organic portion of heme
protoprphyrin ring
structure of protoporphyrin ring
4 pyrroles linked by methenyl bridges
groups/substituents seen in the structure of heme
propionate
vinyl
pyrrole
sharp bands seen when heme absorbs visible lights and read at 400nm absorpotin
Soret band
ano absorption binabasa heme
400nm
substituents attached to pyrolle
methyl
vinyl
propionate
iron in heme bind to how many ligands
6
ano ung 6 na ligands bound to iron ng heme
4 of 6 to N of pyrroles
5th to his F8
6th for oxygen
bond linkinf the first and second oxygen lies at what angle
121 degrees
the state aka deoxy conformation
Tense state
the state aka oxy conformation
Relaxed state
deoxyHb is stabilized in a constrained or tense configuration by
inter and intrasubunit salt bonds
oxygen binds to and pulls the iron toward where
the heme plane
resulting in the straightening of the dome shaped heme
angle of rotation of alpha2/beta2 during oxygenation
15 degrees
what is broken in the heme during oxygenation
8 salt bridges taht stabilize the T state
what is decreased in heme during oxygenation
size of central cavity
what is created during oxygention of heme
new hydrogen bonds in alpha1/bet2 interface
the iron in unoxygented Hb and Mb lies ____ outside the plane of the heme ring
.03 nm
puckering of the heme is directed where
towards proximal his F8
when oxygenated, the iron moves to within ___ of the heme plane
.01 nm
during deoxygenation, the beta chains rotate apart by approximately
.7 nm
the pasok of the heme into the plane during oxygenation si caused by what
stearic repulsion
the second oxygen is oriented _____ the distal his E7
away
partial pressure required for 50% saturation
P50
curve for myoglobin shows what shape
hyperbolic
P50 for myoglobin
2 mm
which has higher affinity, Mb or Hb
Mb @ 2mm P50
curve for hemoglobin shows what shape
sigmoidal
interaction where binding of O2 facilitates binding of additional O2 to other heme group
cooperativity
P50 for hemoglobin
26 torr
why sigmoidal ung hemoglobin
difficult binding of 1sy oxy
easy 2nd and 3rd
difficult for 4th
this provides info on the dgree of cooperativity
Hill coefficient
nH = 1 shows
no cooperativity
nH > 1.0 shows
positive coop
nH < 1.0 shows
neg coop
nH of Mb
1.0
nH of Hb
2.8
refers to the fold change in pO2 required to change Y =0.1 to 0.9 (10% saturation to 90%)
cooperativity index Rx
cooperativity index is computed from
nH
Mb Rx
81
Hb Rx
4.8
causes shift to the right
increase in temp, H protons, 2,3 BPG, altitude
binding of O2 to the T state causes concerted conformational change
Monod Wyman Changuex
allows a serial transformation of the subunits where there exist intermediate transformations between T to R states
Koshland Nemethy Filmer
the glycosylation of Hb requires the ___ type of rearrangement
Amadori
level of HbA1c reflect the mean blood glucose over ____ weeks because halflife of RBCs is 60days
6-8wks
inherited anomalies of Hb synthesis resulting from mutation in the globin genes
hemoglobinopathies
cause of Hb S
glu6 to val
the replacing valine in position 6 produces ___ on teh exterior of the molecule
sticky patch
Hb S causes what shift
rightward
P50 in Hb S
31
which does not contain the sticky patch in transfused blood
deoxy Hb
oxygenation has what effect on Hb S
masking of complimentary site thus prevention of sickling
characterized by reduced of one or more globin synthesis
thalassemia
characteristic products of alpha thalassemia trait
Hb Bart
ilang deletion sa alpha thalassemia-2
one
ilang deletion sa alpha thalassemia trait
2
ilan deletion sa Hgb H
3
absence of alpha chains what dse
Hydrops fetalis
total absence of beta chains what dse
thalassemia major
major end product of aerobic metab
CO2
normal aerobic conditions generate more than _____ of CO2 per day
13mol (.5 to 1kg)
process in transportation of CO2 from tissue to lungs thru circulation
convection
CO2 is _________ than O2
20x more soluble
formed from the rxn of CO2 and H20 catalyzed by the enzyme carbonic anhydrase
HCO3- bicarbonate
enzyme that catalyzes formation of HCO3-
carbonic anhydrase
percentages of CO2 in body
10% as dissolved
20% with proteins
70% bicarbonate
formed from the rxn of CO2 with the amino groups of proteins (like Hgb) within erythrocytes
carbaminohemoglobin
CO2 combines with the what of proteins
terminal NH2 (uncharged, aliphatic)
____________ forms carbamino mmroe readily thatn ________
deoxy Hb; oxy Hb
pH within RBC in carbamino form is
approx. 7.2
major acid produced by the body and acts as its own buffer
carbonic acid
makes hemoglobin an important buffer
isohydric exchange
describes how oxygen conc determines affinity for CO2
Haldane effect
hgih pCO2 unloads O2
Bohr effect
low pCO2 loads O2
reverse Bohr
high pO2 unloads CO2
Haldane
low pO2 loads CO2
reverse Haldane
oxygen shifts the CO2 curve to
right
CO2 curve when PaO2 is @ 95 mmHg
lower curve (down, right)
CO2 curve when PvO2 is @ 40 mmHg
upper curve (up, left)
in CO2 dissoc curve, CO2 content in tissues move from point ___ to ____
A to V
in CO2 dissoc curve, CO2 content in lungs move from point ___ to ___
V to A
chloride shift aka
hamburger effect
function of chloride shift
maintains electrical neutralit/balance
chloride shift is caused by exchange of what
bicarbonate forCL-
chloride ions enter RBC to establish elec neutrality. what effect
Donnan effect
chloride shift movement in tissues
influx of chloride
chloride shift movement in lungs
efflux of chloride
molecule that has a single unpaired electron in an orbital; highly reactive
radicals
action of radicals
initiate chain rxns by stealing an electron from neighboring molecules
free radicals are generated by
homolytic cleavage of covalent bonds
loss of a singl electron
addition of an electron
biradical atom
oxygen
how are the spins of the two solo electron of oxygen
parallel
difficult flipping of an oxygen electron
spin restriction
O2 is capable of accepting how many electrons
4
once O2 accepts one electron, it becomes
superoxide
theory states that an electron cannot readily oxidize a covalent bond because the other electron needs to flip its spin
antibonding
major oxygen metabolites produced by one-electron reduction of oxygen
ROS
superoxide
H2O2
hydroxyl free
which is not a radical
H2O2
eto ung tuloy tuloy na pagbuo ng radicals kapag steal nang steal ung dating radicals
cytotoxic oxidative chain rxn
formed from free O2 by donating an elecctron to another free radical
sueproxide
why can’t superoxide diffuse far from site of origin
limited lipid solubility
superoxide is produced where or when
ETC
generation of hydroxyl free rads by rxn with a transition metal
fenton rxn
rxn of superoxide with H202 to form other ROSs
Haber Weiss rxn
precursor of the powerful oxidzing agent HOCl
H202
powerful ozidizing agent from H2O2
HOCl
rxn when forming H2O2 from O2
dismutation rxn
most toxic ROS
hydroxyl radicals
rxns involved in producing hydroxyl radicals
Fenton nd Haber Weiss
hydroxyl radicals are very damaging because of this intermediate effect
initiation of lipid peroxidation
cis or trans ano mas common na maging radical
cis
wtf question
HOCl is produced in neutrophils during what
respiratory burst
toxicity of HOCl is thru
halogenation and oxidation
how is HOCl formed
myeloperoxidase on CL ions in the presence of H2O2
produced at high oxygen tension from absorption of UV light
O2 singlet oxygen
sppin ng singlet oxygen
anti-parallel
NO is produced by
nitric oxide sythase
NO is synthesized from
argining
anong type ung NO
type 2 inducible
a strong oxidizing agent but not a free radical
ONOO peroxynitrite
peroxynitrie is formed from
superoxide + nitric oxide
kinds of sources of ROS
accidental
physiologic
deliberate
exogenous
coenzyme Q is what kind of source ng rOS
accidental
what ROS is formed in ETC or is an accidental byproduct
superoxide
respiratory burst is what kind of source of ROS
deliberate
process in which cells consume large amounts of oxygen during phagocytosis and release ROS
respiratory burst
how is ROS formed in NADPH oxidase
transfer of electron from NADPH to O2
hydrogen peroxide is formed by what
superoxide dismutase
the formation of HOCl from H2O2 is catalyzed by
myeloperoxidase
oxidatively degrades the neurotransmitter dopamine and geenrate H2O2 at the mitochondrial membrane of certain neurons
monoamine oxidase
generates H2O2 rather than FAD(2H) durind the oxidation of very long fatty acid chains
peroxisomal fatty acid oxidase
an enzyme of purine degradation that can reduce O2 to superoxide or H2O2 in the cytosol
xanthine oxidase
believed to be a major contributor to ischemia-reperfusion injury
xanthine oxidas
xanthine oxidase is believed to be a major contribution to
ischemia-reperfusion injury
formed as intermediates in the pathways for synthesis of many eicosanoids including leukotrienes and prostaglandins
lipid peroxides
xeogenous sources of ROS
ionizing radiation tobacco drugs alcohol inorganic particles gases
this drug has pro-oxidant activity
methotrexate
iron deposition in smokers’ lungs can cause what rxn
Fenton
an antibiotic that may be a source of ROS
nitrofurantoin
chlorine radicals from CFCs are formed thru
photodissociation
steps in membrane attack by lipid peroxy radicals
lipid peroxidation
propragation
degradation
termination
in lipid eproxidation, where does free radicals extract hydrogena tom from
polyunsaturated lipids
lipid radical reacts with O2 and forms what
lipid peroxy radical and lipid peroxide
used as an indicator of fre radical damage in the body
malondialdehyde
termination of the formation of lipid peroxy radicals are caused by
vit E and other lipid-soluble antioxidants
what are the amino acids susceptible to hydroxyl radical attack and oxdiative damage
proline histidine arginine cysteine methionine
main cellular defenses against oxygen toxicity
cellular leve
antioxidant scavenging
nonenzymatic defense
cellular level defense against oxygen toxicity
compartmentalization
metal sequestration
repair mechanism
disabling iron to participate in Fenton rxn
iron sequestration
what are the antioxidant scavenging enzymes
SOD
catalse
glutathione reductase
glutathione peroxidase
this is the primary defense against oxidative stress because superoxide is a strong initiator of chain rxns
SOD
three isoenzyme forms of SOD
cooper-zinc in cytosol
manganese in mitochondria
copper-zinc in extracellular
heme-containing enzyme catalyzing dismutation of H2O2 into water and oxygen
catalase
highest catalase activity can be seen in
kidney and liver
catalse is found principally where
peroxisome
which is better? catalase or glutathione peroxidase? and why
gluta bcoz no oxygen formed from H2O2
amino acids in glutathione
glucine
cysteine
glutamic
catalyzes the reduction of hydrogen peroxide and lipid peroxides by glutathione
glut peroxidase
complete name of glutathione
gamma-glutamylcysteineylglycine
the reactive _______ in glutathione peroxidase reduce H2O2 to water and lipid peroxides to non-toxic alcohols
sulfhydryl groups
what happens to sulfhydryl groups during action of glutathione peroxidase
oxidized to disulfide
glutathione peroxidase is found primarily in
cytosol and mitochondria
reduces oxidized glutathione (GSSG) back to the reduced form
glutathione reductase
major source of glutathione reductase
PPP/HMP
glutathione reductase contains ______ and catalyzes transfer of electrons from NADPH to the disulfide bond of GSSG
FAD
a common structure in non-enzymatic antioxidants
conjugated double bond system that may be an aromatic ring
most widely distributed antioxidant in nature
vit E (tocopherol)
among toxxopherols, this is the most potent
alpha tocopherol
fully oxidized form of tocopherol
tocopheryl quinine
tocopheryl radical is stabilized by the fully substituted benzoquinone ring and does not propagate the radical rxn, there it is an effective __________
radical trap
hydrophilic vitamin and best functions in aqueous environment
vit C
these indirectly scavenges oxygenf ree radicals b recycling tocopherol to the reduced form
chain breaking antioxidant
term applied to the beta carotene
carotenoids
prcursor of vit A
beta carotene
eaxmple of chain breaking antioxidants
vit C
carotenoids
action of carotenoids as antioxidant
reacts with lipi peroxidation products to terminate rxn
what scavenges singlet oxygens
carotenoids
a toxic effect of beta carotene
yellowing of skin @ >20mg/day
group of strucutrally similar compounds containing two spatially separate aromatic rings
flavonoids
sample sources of lavonoids
red win
green tea
chocolate
action of flavonoids
inhibits xanthine oxidase
chelate Fe and Cu
doantes electrons to superoxide or lipid peroxy radicals
maintenance of vit E
endogenous antioxidants
uric acid
melatonin
uric acid accounts for the major ____________________ of plasma
free radical trapping capacity
secretory product of pineal gland
melatonin
functions in the circadian rhythm, light dark signal transduction and sleep induction
melatonin
effectiveness of melatonin as antioxidant is due to its
lack of pro-oxidant activity
joint hydrophilic phobic nature
action of metal chelators as antioxidants
bind iron and copper
example of metal chelators
ferritin
transferrin
cerulopasmin
albumin
transferrin binds
iron
multi subunit protein shell surrounding iron core
ferritin
convert Fe2 to 3
ceruloplasmin
binds copper tightly and iron weakly
albumin
