Unit 6 Flashcards
(156 cards)
1
Q
(hemo/myo) globin: intracellular oxygen transport and storage protein
A
myoglobin
2
Q
(hemo/myo) globin: predominant oxygen carrier in the circulatory system
A
hemoglobin
3
Q
what is the significance of cyt. oxidase’s low Km for oxygen?
A
high affinity for oxygen so ox phos doesn’t have to slow down until there are very low concentrations of oxygen
4
Q
myoglobin: (8 beta sheets/8 alpha helices) with one heme which binds oxygen
A
alpha helices
5
Q
(ApoHb/HoloHb): the protein without prosthetic groups
A
ApoHb
6
Q
ApoHb + 4 hemes
A
HoloHb (hemoglobin)
7
Q
number of atoms of oxygen that can bind to an Hb tetramer
A
8 (because O2 has two oxygen atoms)
8
Q
(R state/T state) favors oxygen binding
A
R state
9
Q
(R state/T state) favors oxygen release
A
T state
10
Q
basis for cooperativity resulting in the sigmoid binding curve for hemoglobin
A
R state–oxygen binding in one site increases the affinity of the other sites
11
Q
(proximal/distal) histidine coordinates Fe in hemaglobin
A
proximal
12
Q
(proximal/distal) histidine H bonds to O2 in hemaglobin
A
distal
13
Q
dark red: (deoxy/oxy) Hb
A
deoxy
14
Q
scarlet red: (deoxy/oxy) Hb
A
oxy
15
Q
diagnostic value of oxy vs deoxy light absorption
A
cyanosis (blue when not oxygenated enough)
16
Q
pulse oximeter measures (venous/arterial) Hb oxygenation
A
arterial
17
Q
pulse oximeter result that is cause for alarm
A
below 90% (95-100 is normal)
18
Q
how does the pulse oximeter measure % oxygenation
A
uses ratio of oxy:deoxy, based on absorption spectra
19
Q
the pressure at which binding is half-maximal, or the pressure value at which 50% of the maximal oxygen load has been released
A
P50
20
Q
(myo/hemo) globin: hyperbolic curve
A
myoglobin
21
Q
Mb binds O2 under conditions in which Hb releases it, due to Hb’s ______ shaped curve
A
sigmoid (sophisticated O2 transport system)
22
Q
(allostery/cooperativity): effect in which what is happening at promotes the same thing happening at another identical site
A
cooperativity (allostery involves “other” active sites and is more broad)
23
Q
negative effectors shift the Hb curve to the (R/L)
A
right, stabilize T state
24
Q
BPG stabilizes the _ state of Hb
A
T state, shifts curve right (binding site for BPG only exists in T state)
25
people in high altitudes have (higher/lower) levels of BPG to promote increased oxygen unloading and delivery to tissues
increased levels of BPG
26
low pH, high [H+], (raises/lowers) affinity for O2
lowers affinity
27
lungs: (higher/lower) pH to load more O2
higher pH (CO2 is low due to exchange with inhaled air)
28
muscles: (higher/lower) pH to unload more O2
lower pH
29
high CO2 (raises/lowers) pH, which (raises/lowers) affinity for O2
lowers pH, lowers affinity
30
carbamylation stabilizes the _ state of Hb
T state
31
_ and _ synergize to unload O2 in the capillary where O2 is needed
H+ and CO2
32
HbF does not bind BPG as well so O2 affinity is (lower/higher) and curve shifts (R/L)
affinity is higher, curve shifts left
33
individuals with a Glu -> Val substitution on the beta chain suffer from:
sickle cell anemia--creates a hydrophobic pocket resulting in aggregates)
34
HbBARTS: (adults/fetus) thalassemia
fetus--gamma tetramer forms
35
HbH: (adults/fetus) thalassemia
adults--insufficiency of alpha chains so beta tetramer forms
36
hemoglobin in which the heme iron has been oxidized the ferric state
methemoglobin (does not bind oxygen, leads to cyanosis)
37
______ (Hemoglobinopathy): can be caused by mutations in Hb that stabilize the oxidized form, defect in enzyme CYB5R that normally reduces it back to Hgb, chemical agents such as sodium nitrite
methemoglobinemia
38
what test is used to detect abnormal Hb
non denaturing (native) gel electrophoresis
39
heme possesses a ____ ring, which is constructed from four pyrrole rings
porphyrin ring--they form metal chelates with metal ions
40
order of eight side chains in the protoporphyrin:
MVMVMPPM (methyl, vinyl, propionate)
41
the isomer of protoporphyrin in heme:
protoporphyrin IX
42
heme (a/b/c): modification of the number 2 vinyl group
a
43
heme (a/b/c): no modifications from MVMVMPPM
b
44
heme (a/b/b): covalently bound to Cys residues of proteins through the two vinyl groups
c
45
two precursors of heme
glycine and succinyl CoA
46
at which step of the heme synthesis pathway is it regulated?
first step (glycine and succinyl CoA -> ALA), main target of control is ALA synthase enzyme
47
accumulation of which intermediate in heme synthesis causes symptoms of lead poisoning?
ALA (lead inhibits the enzyme ALA dehydrase by replacing the Zn cofactor so ALA builds up)
48
two enzymes in heme synthesis that are inhibited by lead
ALA dehydrase, ferrochelatase (second and last steps in the pathway
49
two sites of heme biosynthesis
liver (use as prosthetic group for cytochrome P450) and erythroid cells (use heme for hemoglobin)
50
(liver/erythroid) cells: synthesize heme at one time in their life and in vast quantities
erythroid
51
(liver/erythroid) cells: heme is required in varying amounts throughout the cell's lifetime, synthesis is tightly controlled
liver
52
ALA synthase step in heme synthesis is feedback-inhibited by: (four pathways)
1-repression of mRNA synthesis
2-inhibition of translation of the ALA synthase mRNA
3-inhibition of import of the ALA synthase protein into mitochondria
4-direct inhibition of enzyme
53
genetic deficiencies in heme metabolism, enzymes are partially defective
porphyrias
54
(hepatic/erythropoietic) porphyria: come as attacks that are induced by something
hepatic
55
(hepatic/erythropoietic) porphyria: chronic condition
erythropoietic
56
(hepatic/erythropoietic) porphyria: hallmarks are sensitivity to sun and anemia
erythropoietic
57
(congenital erythropoietic porphyria/protoporphyria): partial deficiency in ferrochelatase, autosomal dominant
protoporphyria
58
(congenital erythropoietic porphyria/protoporphyria): deficiency in uroporphyrinogen III co-synthase, autosomal recessive
congenital erythropoietic porphyria
59
steroid therapy, alcohol, estrogens, barbituates: cause build up of which intermediate in the heme synthesis pathway
ALA
60
(acute intermittent porphyria/porphyria cutanea tarda): deficiency in uroporphyriogen decarboxylase, sporadic or autosomal dom, precipitated by alcohol or use of contraceptive pill
porphyria cutanea tarda--asymptomatic until liver disorder is imposed, then photosensitivity
61
(acute intermittent porphyria/porphyria cutanea tarda): most common porphyria, partial deficiency of PBG deaminase, causes accumulation of ALA and porphobilinogen
acute intermittent porphyria
62
lifespan of RBC
120 days
63
where does removal of aging RBCs occur
spleen (reticular endothelial cells)
64
what is the role of haptoglobin, hemepexin, and transferrin
haptoglobin binds methemoglobin dimers and hemepexin binds free heme. Transferrin binds free iron. All to prevent loss of iron via kidney
65
product in first step of heme degradation (and color)
biliverdin-green
66
enzyme in first step of heme degradation
heme oxygenase
67
location in first step of heme degradation
spleen, endoplasmic reticulum
68
product in second step of heme degradation (and color)
bilirubin (yellow)
69
enzyme in second step of heme degradation
biliverdin reductase (uses NADPH for reduction)
70
location in second step of heme degradation
spleen (reticular endothelial cells)
71
health benefit of bilirubin
antioxidant--binds free radicals in serum
72
location of third step of heme degradation
liver
73
purpose of third step of heme degradation
conjugate with two sugars to make it water soluble
74
Crigler-Najjar syndrome is due to a deficiency in what enzyme? results in severe jaundice
UDP-glucuronyl transferase (conjugation of bilirubin)
75
neonatal jaundice is a temporary condition due to the production of insufficient levels of what enzyme
UDP-glucuronyl transferase (conjugation of bilirubin)
76
therapy for neonatal jaundice
phototherapy--irradiation with fluorescent lights
77
conjugated bilirubin passes from the liver into the bile _____ to the gall bladder to the intestinal tract
canaliculi
78
intestinal bacteria convert conjugated bilirubin to a series of ______
urobilinogens
79
urobilinogens are colorless, but oxidation leads to the formation of urobilin, which colors:
urine and feces
80
bilirubin binds to ___ (protein) to be transported from the blood to the liver to be conjugated
albumin
81
two possible causes of blockage of bile duct
pancreatic cancer, gall stones
82
observable symptom of blockage of bile duct
relatively colorless feces, urine
83
example of (prehepatic/hepatic/posthepatic) jaundice: sickle cell anemia, Rh incompatibility with mother
prehepatic
84
example of (prehepatic/hepatic/posthepatic) jaundice: prevents uptake and conjugation of bilirubin
hepatic
85
(prehepatic/hepatic/posthepatic) jaundice: build up of unconjugated bilirubin in blood
prehepatic
86
(prehepatic/hepatic/posthepatic) jaundice: build up of conjugated bilirubin
post
87
accumulation of bilirbuin where it doesn't belong
jaundice
88
two molecules for iron storage
ferritin and hemosiderin
89
hemosiderin is a degraded form of ____
ferritin
90
an increase in iron entering tissues results in (an increase/a decrease) in ferritin content
increase
91
where are the body's iron reserves
liver, bone marrow, skeletal muscles, spleen
92
where is iron used to make new RBCs
erythroid marrow
93
where are RBCs broken down and iron is released
reticulo endothelial cells in the spleen
94
which protein moves the iron from the spleen to the bone marrow
transferrin
95
how does transferrin act as an antimicrobial
binds free iron to prevent bacteria from using it as food
96
ferro-transferrin binds a receptor on the cell membrane at pH _
7
97
what happens to ferro-transferrin inside the clathrin coated pits when the pH drops to 5
iron dissociates from the transferrin
98
transferrin cannot bind receptor in pH _ if iron is not bound, but it can bind its receptor without iron bound in pH _
cannot bind receptor in pH 7 without iron
| can bind receptor in pH 5 without iron
99
primary cause of polymerization of HbS
deoxygenation
100
fever, acidosis, and dehydration (increase/decrease) rate and amount of sickling
increase
101
polymerization of HbS causes (increased/decreased) RBC destruction
increased, and anemia
102
what causes pain during sickle cell dz
blockage of capillaries (can also cause organ dysfunction)
103
current childhood death rate for SC dz versus historical
3% versus 30%
104
severity of SC dz (is/is not) predictable based on type
not predictable--great variation
105
why are infants protected from effects of SC dz
HbF for first four months of life (no beta chains)
106
when did newborn screening for SC dz become universal in the US
last decade (started in 1970 but not universal)
107
three benefits of newborn screening for SC dz
diagnosis, education, prophylactic antibiotics piror to risk of sepsis (primary benefit: start penicillin and recognize fever as first sign of sepsis)
108
what test is used for newborn screening
heel prick > gel electrophoresis (HbS vs HbC vs HbA)
109
HbC and HbS are distinct mutations of the _th amino acid on the beta chain of Hb
6th
110
(sickle cell trait/homozygous sickle cell anemia) is a carrier state, clinical complications very rare, genetic implications
trait
111
(sickle cell trait/homozygous sickle cell anemia) 2/3 of patients, most severe
anemia
112
variant of SC disease: one parent AS and one AC, milder disease, C does not sickle but increases viscosity
hemoglobin SC disease
113
variant of SC disease: HbS from sickle gene, little or no HbA, can be very severe
sickle beta thalassemia--ineffective beta thalassemia gene
114
most deaths from bacterial sepsis due to sickle cell within first _ hours of symptoms
8 hours
115
severe complication of sepsis due to SC dz that results in skin necrosis and can result in the loss of digits and severe tissue loss
pupura fulminas
116
vaso occlusive episodes in SC dz cause:
excruciating pain, must be treated with a lot of morphine, transfusion usually not helpful
117
presentation of vaso occlusive episode for SC dz in first two years of life
hand foot syndrome--swelling
118
in children with SC dz, strokes are caused by (hemorrhage/thrombosis)
thrombosis (hemorrhagic strokes in adults)
119
acute chest syndrome refers to
sickle cell disease--diffuse and bilateral loss of airspace, resp failure
120
how to avoid death from acute splenic sequestration crisis in SC patients
teach patients/parents to palpate for spleen
121
if parents are considering termination in genetic counseling for SC dz, what test can you offer
prenatal diagnosis via amniocentesis
122
why would you want to harvest placental blood from newborn sibling of a child with SC dz
safest possible transplant
123
first therapy which can effectively reduce incidence of SC dz complications
hydroxyurea (mild chemotherapeutic agent)
124
only available cure for SC dz
bone marrow transplant
125
candidates for bone marrow transplant for SC dz
severe acute chest syndrome, frequent pain episodes
126
future goal of treatment for SC dz
viral vector to insert normal beta chain via benign viral illness without immunosuppression of transplant
127
on which chromosome is the SC dz mutation
11 (A>T Glu>Val conversion, beta chain)
128
(reversibly/irreversibly) sickle cells constitute 2-40% of circulating RBCs in homozygous SC anemia
irreversibly (stay that way even when well oxygenated, results in hemolysis and vasoocclusion)
129
three steps to vasoocclusion in SC dz
1-endothelial activation
2-WBC adhesion (extra adhesive in SC pt)
3-RBC/WBC interactions
130
survival probability is (higher/lower) in SC patients with 3 or more episodes per year
lower
131
three places where erythropoiesis occurs throughout life
yolk sac, fetal liver, bone marrow
132
C-MYB is a hematopoeitic txn factor which (stimulates/represses) the production of gamma globin
represses
133
BCL11A on chromosome 2 is a txn (stimulator/repressor) and gamma globin (enhancer/silencer)
repressor, silencer
134
role of BCL11A and MYB
switch from gamma to beta globin
135
(alpha/beta) chain coded on chromosome 16
alpha (beta on 11)
136
high presence of HbF (increases/reduces) severity of SC
reduces
137
how does SC dz increase reactive oxygen species (ROS) in the blood
vasoocclusion causes ischemia so xanthine oxidase is produced. xanthine oxidase converts O2 to superoxide when tissue is reperfused
138
what does NFkB activation lead to
inflammation (increase expression of cytokines)
139
NFkB activation >increased expression of adhesion molecules on surface of endothelial cells and leukocytes > causes what?
heterotypic adhesion between cells > vasoocclusion
140
NFkB activation > (increased/decreased) NO availability (causes what)
decreased NO results in abnormal endothelial dependent vasodilation
141
Sickle cells have (increased/reduced) glutathione
reduced >>would protect against ROS damage
142
glutathione levels are (inversely proportional/proportional) to density of sickle cells
inversely. so when glutathione levels drop, sickling increases
143
peroxide levels are (decreased/increased) in SC dz
increased
144
to maintain phospholipid asymmetry in plasma membrane, flippases must be (more/less) active than scramblases
more (when phosphoserine gets to the outside of cell it can bind clotting factors or as a recognition site for macrophages)
145
phosphoserine on the external plasma membrane (increases/decreases) the life of a sickle cell
decreases--attracts macrophages
146
which proteins connect spectrin and actin on the RBC membrane skeleton
protein 4.1 and adducin
147
oxidative stress causes the RBC membrane skeleton to:
become locked in place
1-actin can never depolymerize (S-S bridge from cysteines)
2-spectrin-4.1-actin is tightly associated
148
oxidative stress (increases/reduces) alpha-spectrin ubiquitination in the RBC membrane skeleton
reduces
149
sickling (inhibits/activates) a cation leak channel, resulting in a (gain/loss) of intracellular Ca
activates leak channel, intraceullar Ca increases
150
the sickling induced cation leak channel causes a (gain/loss) in intracellular K and Mg
loss
151
Gardos channel for (K/Ca) ion, stimulated by (K/Ca) ion
for K, stimulated by Ca
152
sickling induced cation leak channel results in a net ion movement (into/out of) cell, and water movement (into/out of) cell
out of, cell dehydrates
153
NAC antioxidant treatment (lowers/raises) glutathione levels in SC dz
raises glutathione levels
154
NAC antioxidant treatment (lowers/raises) K efflux in SC dz
lowers K efflux (reduces cell dehydration)
155
NAC antioxidant treatment (lowers/raises) incidence of the beta-actin disulfide bridge in SC dz
lowers (so cells are not locked in sickle state)
156
how does hemolysis in SC dz affect NO
Hb released in plasma binds free NO and reduces the amount of NO available for vasodilation
