MCP 11L Flashcards
1
Q
Most oxygen in the body is used for oxidative phosphorylation by the enzyme _______
A
Cytochrome oxidase
2
Q
The Km for Cytochrome oxidase is _____
A
Less than 1 torr
3
Q
Hemoglobin is a tetrameric protein with the quaternary structure ______
A
alpha 2 beta 2 heterodimers
4
Q
The distal heme pocket is where _____ binds
A
O2
5
Q
Less than _____ % oxygen as measured by a pulse oximeter is cause for alarm
A
90%
6
Q
Myoglobin has a _____ shaped binding curve while hemoglobin has a _____ shaped binding curve
A
Hyperbolic
Sigmoidal
7
Q
The p50 for myoglobin is _____ torr while the p50 for Hemoglobin is _____ torr
A
2.6 torr
26 torr
8
Q
Hemoglobin in the ____ state oxygen is not bound. In the ___ state favors oxygen binding
A
T-state
R-state
9
Q
An effect of something happening at another site on an active site is called _____
A
Allostery
10
Q
A type of allostery in which what is happening at one site promotes the same thing to happen at another identical site is called _____
A
Cooperativity
11
Q
_____ binds to an allosteric site on hemoglobin in the T state (increasing/decreasing) the O2 affinity and shifting the curve to the right
A
BPG
Decreasing
12
Q
A low pH shifts the hemoglobin O2 binding curve to the (right/left)
A
right
13
Q
CO2 effects Hb binding by the synergy of both the Bohr effect and by ________ of the N-terminal amino groups of blood proteins
A
Carbamylation
14
Q
Fetal Hemoglobin has the subunits
A
Alpha-2 Gamma-2
15
Q
_______ is a defect in the production of alpha chains of hemoglobin
A
Alpha thalasemia
16
Q
______ is a defect in the production of beta chains and can be either “major” or “minor”
A
Beta Thalasemia
17
Q
Name the Wild Type of Hemoglobin
1) Normal Adult (Alpha-2 Beta-2)
2) Adult with Fetal gamma (Alpha-2 Delta-2)
3) Fetal Hemoglobin (Alpha-2 Gamma-2)
A
1) HbA
2) HbA2
3) HbF
18
Q
Name the Variant Type of Hemoglobin:
1) Sickle cell (Alpha-2 Beta*-2)
2) Mild Sickle Cell (Alpha-2 Beta x-2)
3) Alpha Thalsemia (Beta-4)
4) Gamma 4
A
1) HbS
2) HbC
3) HbH (B4)
4) Hb Barts
19
Q
The two basic building blocks of Heme are _____ and _____
A
Glycine and Succinyl CoA
20
Q
Hemoglobin is synthesized by the enzyme ______ to make delta aminolevulinate (ALA)
A
delta Aminolevulinate synthase (ALAS)
21
Q
The gamma subunit of HbF bind BPG (more/less) tightly and has a (higher/lower) O2 affinity than the adult Beta subunit of HbA
A
Less tightly
Higher affinity
22
Q
The hemoglobin protein of alpha and beta chains WITHOUT the prosthetic Heme group is called
A
ApoHb
23
Q
Heme is Fe chelated by _______
A
Protoporphyrin IX
24
Q
Hemoglobin in the T state binds O2 with (low/high) affinity
A
Low
25
Hemoglobin in the R state binds O2 with (low/high) affinity
High
26
BPG, CO2 and H+ all (increase/decrease) Hemoglobins O2 binding affinity
Decrease (releases O2)
27
BPG stabilizes the (T/R) state
BPT stabilizes the T state, decreases O2 affinity
28
Carbamylation of N-terminal amino groups stabilizes the (R/T) state of hemoglobin
T state (releases O2)
29
Fetal HbF has a (higher/lower) binding affinity than maternal (HbA)
Higher
30
Hemoglobin in which the iron in the heme group is in the Fe3+ (ferric) state and unable to carry oxygen
Methemoglobin
31
A disease with too much methemoglobin is called
Methemoglobinemia
32
Around the ring of protoporphyrin IX, what are the side chains (list 8)
MVMVMPPM
M=Methyl
V=Vinyl
P=Propionate
33
Changing the position 2 side group of Heme B makes ______
Heme A
34
Covalently bonding a cystine residue to Heme B makes ______
Heme C
35
Glycine and Succinyl CoA are combined to form ______
Gamma-Aminolevulinate
| ALA
36
Two ALA (Gamma-Aminolevulinate) are combined to form ______
Porphobilinogen (PBG)
37
The Zn cofactor of ALA can be replaced by ______ leading to a failure to form Porphobilinogen
Lead
38
Four molecules of Porphobilinogen (PBG) combine to form ______, a tetrapeptide
Uroporphyrinogen I
39
Uroporphyrinogen I is converted to Uroporphyrinogen III and then ________
Protoporphyrin IX
40
Heme is made in the liver in order to make the enzyme ______
Cytochrome P450
41
Genetic deficiencies in heme metabolism are called _____
Porphyrias
42
Name the disease:
| Deficiency in uroporphyrinogen III co-synthase.
CEP
| Congenital erythropoietic porphyria
43
Name the disease:
Partial deficiency in ferrochelatase
Accumulation of (soluble) Coproporphyrinogen III
Less severe than CEP
Protoporphyria
44
Name the disease:
| Caused by partial (50%) deficiency of porphobilinogen (PBG) deaminase leading to accumulation of ALA and PBG
AIP
| Acute Intermittent Porphyria
45
Name the disease:
Deficiency in uroporphyrinogen decarboxylase in liver. Leads to photosensitivity. Precipitated by ethanol or contraceptive pill.
PCT
Porphyria Cutanea Tarda
(a porphyria of the skin late in life)
46
PBG stands for ____
Porphobilinogen
47
Removal of aging red blood cells occurs in the _____
Spleen
48
_____ binds methemoglobin dimers for storage
Haptoglobin
49
_____ binds free heme with higher afinity than any protien for storage to prevent iron loss
Hemopexin
50
_____ binds free iron in plasma to prevent iron loss
Transferrin
51
Biliverdin is reduced by NADPH to ______
Biliruben
52
Biliruben diglucuronide is called _____
Conjugated bilirubed
53
Massive breakdown of red blood cells resulting in overproduction or free bilirubin. The liver cells cannot conjugate bilirubin at the rate it enters the liver. Hence build up of conjugated bilirubin in blood
Prehepatic jaundice
54
Disease condition of the liver (eg hepatitis, cirrhosis) that prevents uptake or conjugation or bilirubin
Hepatic jaundice
55
Blockage of bile flow out of the liver and into the intestinal tract, buildup of conjugated bilirubin
Posthepatic jaundice
56
Jaundice:
High conjugated bilirubin
(Prehepatic/intrahepatic/posthepatic)
Intrahepatic or posthepatic
57
Jaundice:
AST or ALT high
(Prehepatic/intrahepatic/posthepatic)
Intrahepatic
58
Jaundice:
ALP high
(Prehepatic/intrahepatic/posthepatic)
Posthepatic
59
Jaundice:
Urine bilirubin present
(Prehepatic/intrahepatic/posthepatic)
Intrahepatic or posthepatic
60
Jaundice:
Urine urobiliruben present
(Prehepatic/intrahepatic/posthepatic)
Prehepatic or intrahepatic
61
Red blood cells are made in the _____ and degraded in the _____ so iron must be transported back to the marrow
Marrow
| Spleen
62
______ is a glycoprotein synthesized in the liver specialized for iron transport. It lives in blood plasma.
Transferrin
63
______ is a degraded form of ferritin
Hemosiderin
64
______, a product of blood degradation, is one of the body's major antioxidents
biliruben
65
_____ is a deficiency in UDP-glucuronyl transferase and results in serve jaundice
Crigler-Najjar Syndrome
66
Neonatal Jaundice can be treated by ________, since the bilirubin breakdown products are more soluble than bilirubin and can be excreted by the liver into bile without conjugation
Phototherapy: irradiation with fluorescent light
67
Conjugated Biliruben passes from the liver to the _____ the _____ to the intestinal tract
To the bile canaliculi, to the gall bladder, to the intestinal tract
68
In the intestinal tract, bacteria convert sugary conjugated bilirubin into colorless _____.
Urobilinogens
69
Urobilinogens made by bacteria in the intestines are oxidized to _______, responsible for the color of feces
Urobilins
70
The two major iron storing proteins in the body are _____ and it's degraded form _____
Ferretin
| Hemosiderin
71
The body moves Iron from the Spleen back to the marrow by the iron transporter ______
Transferrin
72
Absorption of iron is done by the process of ____ ____ endocytosis of iron containing Ferro-transferrin
receptor mediated endocytosis
73
Ferro-transferin and its receptor are taken in by endocytosis in vesicles called ______pits where the pH is lowered and the iron dissociates
clathrin coated pits
74
As pH decreases, transferrin tend to (release/sequester) Iron
Release
75
The alpha globin cluster is on chromosome _____
16
76
The Beta globin cluster is on chromosome _____
11
77
The pain associated with sickle cell disease is due to ______
tissue ischemia: blockage of capillaries
78
The primary cause of polymerization of hemoglobin S is ______, but fever, acidosis and dehydration will all increase the rate of sicking
Deoxygenation
79
Norm red cells have a diameter of _____ microns and can transverse capillaries as small as _____ microns
7
| 3
80
Hemoglobin C and Hemoglobin S are distinct mutations of the 6th amino acid on the (alpha/beta) chain of hemoglobin
Beta
81
Individuals with sickle cell trait (HgAS) produce more (HgA/HgS)
55-65% HgA
82
Sickle cell with the genotype SC affect 1/4 of patients and is (milder/more severe) than those with the genotype SS
Milder
83
For patients with SS painful swelling in the hands and feet in the first 1-2 years of life is called ______ syndrome
Hand-Foot Syndrome
84
Sickle Cell Disease (increases/decreases) the risk of stroke
Increases
85
Acute Chest Syndrome is commonly associated with _____
Sickle Cell Disease
86
Sickle Cell anemia causes enlargement of what organ?
Spleen
87
Sickle Cell anemia can be treated with the mild chemotherapeutic agent ______ by increasing ______
Hydroxyurea
| HbF
88
The only way to "cure" sickle cell disease is by ______
Bone Marrow Transplant
89
To determine if a patient affected with sickle cell is a candidate for a bone marrow transplant, you should _______
Test her siblings HLA (Histocompatability Locus Antigens)
90
A SS patient has O2 sat. 84%. After 2L nasal cannula, O2 is 88% What to do?
Give the patient a transfusion
91
(single/multiple) amino acid substitutions in the beta globin chain cause sickle cell anemia
single
92
SS Sickle cell anemia is caused by a single amino acid substitution of glutamic acid to _______
valine
93
Sickle cells that are permanently locked in the sickle shape are called _____
ICS
| Irreversible sickle cells
94
During a sickle cell event, ischemic cell release a burst of _______ when blood profusion is restored
ROS
| Reactive Oxygen Species
95
Upon repurfusion ________ converts oxygen into superoxide radicals
Xanthine Oxidase
96
The burst of ROS during reperfusion leads to _______ and _____
Inflammation and
| increased expression of adhesion molecules on endothelial cells (bigger plug)
97
Two transcription factors that modulate the switch from fetal to adult hemoglobin are ______ and _______
HBS1L-MYB
| BCL11A
98
Normal fetal hemoglobin represents _____ to ______ % of adult hemeglobin. Increasing to ______ % could be therapeutic of SS patients.
0.1%
1%
20%
99
Sickle cell RBCs contain (more/less) O2 radicals than normal blood cells
3X more
100
In the RBC the most important of non-enzymatic antioxidant is ____
reduced glutathione (GSH)
101
SS are in double jeopardy because of increased ______ and decreased _______
```
increased OH- radicals
decreased glutathione (GSH)
```
102
In RBCs, oxidative stress inhibits ______ and activates ______ which places (-) charged phosphates on the outside where it can associate with Ca2+ and clotting factors
inhibits flippase
| activates scramblase
103
The three membrane proteins responsible for holding a RBC's shape are ____ ____ and ____
spectrin
actin
protein 4.1
104
The RBC sickle shape gets locked due to 1)______ and 2) _______ both caused by increased oxidative stress
beta-actin disulfide bridge
| diminished alpha spectrin ubiquitination which creates spectrin-actin complexes
105
Activation of the sickling induced leak channel increases intracellular ______ and decreases _______ and _____
intracellular free Ca2+
| decreases K+ and Mg+
106
The net outflow of ions from and RBC (increase/decreases) osmotic pressure causing _____
decreases osmotic pressure
| dehydration
107
Lowering intracellular GSH leads to increased oxygen radicals and damage to the _____ channels and increased ______ loss
Gardos
| K+
108
______ is a drug that increases intracellular GSH levels, maintaining Gardos Channels and K+ retention
NAC (N-acetylcystine)
109
Four current treatments for SS disease are 1. 2. 3. 4.
1. Antibiotics
2. Analgesics
3. Hydroxyurea
4. Bone marrow transplant
110
Each hemoglobin has 36 His residues. How many are bonded to Heme?
4
| Each subunit has 1 His coordinated to heme
111
As substrate concentration [S] increases, initial reaction velocity (increases/decreases)
increases
112
A reaction velocity (v) vs. Substrate Conc. [S] curve is typically shaped like a _______
rectangular hyperbola
113
Enzymes that follow the typical rectangular hyperbola graph shape can be fitted with the ________ equation
Michaelis-Menten
114
E + S ES -----> E + P
| What rates do we measure?
k1, k2, and k3
115
(Vmax) * ([S] / ([S] + Km)) = ?
=v
| Michaelis-Menten equation
116
Km = [S] when v = ______ of Vmax
1/2
117
The catalytic rate of an enzyme is most sensitive to [S] when [S] is (<< , = , >, >>) Km
much less than <<
| steepest part of hyperbola
118
fES = v/Vmax
fES = [S] / ([S] + Km)
can calucualte
fraction of total enzyme bound to substrate
119
Knowing Km allows you to calculate _____ at any given [S]
the fraction of Substrate bound at any given substrate concentration
120
When does Km approximate Kd?
When K2 >> K3
121
Km approximately = Kd when _____
K2 >> K3
| when dissociation of the ES complex is the limiting rate
122
In M-M kinetics, k3 is also called kcat or the _____ number
turnover
123
The maximum velocity achievable for a specific concentration of enzyme is called _____
Vmax
124
Higher kcat /Km implies (more/less) efficiency
More
125
How quickly the ES complex is used is described by _____
kcat
126
How much ES complex is available is described by _____
Km
127
A Lineweaver-burke plot is a ______ plot that linearlizes the Michaelis-Menten equation
double reciprocal
128
1/v = 1/Vmax + (Km/Vmax)*(1/[S]) is called _____
Linweaver-Burk transformation
129
These inhibitors compete with the substrate for binding site activity.
Competitive
130
These inhibitors bind to a site on the enzyme other than the active site
Non-competitive
131
Ki = [E]*[I] / [EI] is the ____
Disociation constant equation
132
A higher Ki implies (stronger/weaker) inhibition
weaker
133
The lineweaver-burk plot with a competitive inhibitor will have the same ____ intercept, but different ____ intercept
same y
| different x
134
Non-competitive inhibitors will have the same ____ intercept, but different ____ intercept
same x
| different y
135
Histamine is a (cytokine/interferon)
cytokine
136
With _____ inhibition, Km appears to increase in presence of the inhibitor, but Vmax does not change
competitive
137
With ____ inhibition, Km does not change, but Vmax appears to decrease
Non-competitive
138
One of the most important amino acids in acid-base catalysis is _______ due to its amphoteric nature
histadine
139
______ degrades acetylcholine in the synaptic cleft and thus help to control transmission of nerve impulses
AChE
| Acetylcholinesterae
140
Nerve gases such as _____ are irreversible inhibitors of acetylcholinesterase
Sarin
141
For proteolysis, the RDS is formation of the _______ intermediate due to the energy required to pass though the tetrahedra intermediate
the acyl-intermediate
142
Most drugs are (reversible/irreversible) inhibitors
reversible
143
Penicillin is a _____ inhibitor of glycopeptide transpeptidase
suicide
144
Accumulation of photoreactive uroporphyrinogen I and Coproporphyrinogen I
(Photosensitivity --> werewolf ledgend)
CEP
| Congenital Erythropoitic porphyria
145
The best inhibitors mimic the ______ state conformation of the substrate
transition state
146
The residues that make the catalytic triad for a serine protease are ______, ______ and _____
aspartate, histadine, serine
147
The two amino acids used in an aspartyl protease are ____ at the active site
two aspartates
148
HIV protease is a _____ type protease essential for viral maturation
aspartyl protease
149
The HIV aspartyl protease is different from the Eukaryotic heterodimer aspartyl protease because it is a smaller, symmetric ______
homodimer
150
The transition state for peptide cleavage by an aspartyl protease is a ______ type geometry
tetrahedral type geometry
151
Substrate-based design means that the designed inhibitor will bind the enzyme's _____ site
active site
152
Due to the high error rate in reverse transcriptase, ______ is a major issue for HIV therapy
drug resistance
153
In management of HIV, HAART stands for ____
highly active antiretroviral therapy
154
The HCV lifecycle includes a _____ protease that is good target for designed drugs
Serine
155
Positive modulators (allosteric activators) will (increase/decrease) K0.5
decrease
| shift sigmoidal curve left
156
Negative modulators (allosteric inhibitors) will (increase/decrease) K0.5
increase
| sift sigmoidal curve right
157
ATP is allosteric activator for Aspartate transcarbamolyase (ATCase) while _____ is an allosteric inhibitor that increases K0.5
CTP
| =Cytidine triphosphate
158
CTP is an allosteric inhibitor of ATCase that binds at the non-active site to the (low/high) affinity conformation or ATCase
low
159
ATP is an allosteric activator of ATCase that binds allosterically to the (low/high) affinity conformation or ATCase
high
160
An enzyme kinase does ______, which activates an enzyme
phosphorylation
161
An enzyme phosphotase does ______, which inactivates and enzyme
dephosphorylates
162
Some Enzymes can be switched on and off by phosphorylating and _________ them
dephosphorylating
163
An inactive precursor form of a protease that can be activated by proteolytic cleavage is called a ______
Zymogen
164
Activation of trypsinogen to make trypsin is catalyzed by ________ a protease on the surface of the duodenum
enteropeptidase
165
Many of the enzymes involved in blood clotting are ______ proteases
serine
166
Factor _____ is the protein missing in hemophiliacs
VIIIa
167
Vitamin ___ is a co-factor for the enzyme that catalyzes the addition of the γ-carboxyl group to GLA
K
168
Anti-coagulants such as warfarin or coumadin are competitive inhibitors for vitamin ___
K
169
Inhibition of Vitamin K by warfarin or coumadin prevents _____ foramtion
GLA
| γ-carboxyl glutamate
170
TPA is often called a ______
clot buster
171
Plasminogen is converted to plasmin by _____
TPA
| tissue plasminogen activator
172
Fibrin is converted to clot forming peptides by _____
Plasmin
173
α-1 antitrypsin is an inhibitor of ____
elastase
174
Elastase is secreted by ______
neutrophiles
175
Inhibits clotting by binds to the active site of serine proteases
AT III
| anti-thrombin
176
AT III can be stabilized by ______
Heparin
177
AT III deficiency lead to excessive _____
Clotting (thrombosis)
178
elastase build up in the the lung with _______ deficiency
α-1 antitrypsin
179
Too much elastase in the lungs causes ______
emphysema
| COPD
180
PKA is regulated by interaction with _____
cAMP
181
ALT (or SGOT) can detect _____
viral hepatitis
182
Amylase can be used to detect ____
acute pancreatitis
183
Creatine Kinase can be used to detect _____
muscle disorders / MI
184
Lactase dehydrogenase can be used to detect _____
Liver disease
185
Lipase can be used to detect _____
Acute pancreatitis
186
Phosphotase acid can be used to detect ____
carcinoma of prostate
187
Phosphotase alkaline can be used to detect _____
bone disorderdes, obstructive liver disease
188
MI can lead to increased plasma ____, ____ and ____
CK-2 (Creatine kinase)
AST (asparate aminotransferase)
LDH-1 (lactate dehydrogenase)
189
The small group of proteins that inhibit proteases are called _____
serpins
190
Why do enzyme assays at saturating [substrate]?
Because Δ[S] and Δ[P] will be linear so we can measure Vmax if we know the [enzyme]
191
two or more enzymes with identical function but different structure are called
isozymes
192
Acute pancreatitis can be detected by both ____ and ____
amylase and lipase
193
Heme biosynthesis is regulated at the level of ____ synthesis
ALA
194
When heme is degraded the toxic gas ____ is produced
CO
| Carbon monoxide
195
The rate limiting step in heme synthesis is the enzyme _____ synthase
delta-Aminolevulinte synthase
| delta-ALA
