Biochem Flashcards
(273 cards)
1
Q
2,3 - BPG binding site/type
A
ionic bond with Beta subunit of HgbA
2
Q
high methionine = which aa now essential
which enzyme def
name
A
cysteine
defect in cystathione synthetase
homocystinuria
3
Q
Lens sublixation down and in
A
homocysteinuria
4
Q
Lens sublixation upward
A
Marfans
5
Q
Enzyme def in homocysteinuria and tx(2)
A
- Cystathionine synthase (with B6)
tx: cysteine, up up B6 - homocysteine methyl transferase (?aka methionine synthase)(with B12)
tx: methionine, B12
6
Q
symp homosysteinuria
A
intellectual dis osteoporosis TALL stature lens sublixation (down and in) thromosis atherosclerosis (MI, stoke)
7
Q
homeless, increased fatigability, exertional dsypnea, LE edema, cardiac dilation, increased CO… nutrient def
A
B1 (thiamine)
8
Q
wrinkles - cause
A
decreased collagen fibril production - net loss of dermal collagen and elastin
9
Q
RNA between 74 and 93 nucleiotides
A
tRNA
*contains unusual nucleosides such as pseudouridine and thymidine
10
Q
3’ end of tRNA
A
- CCA sequence (recognition sequence by proteins)
- terminal OH
- binding site for aa
11
Q
acceptor stem of tRNA
A
3’/5’ ends
12
Q
enzyme that catalyzes loading of tRNA with aa
A
aminoacyl tRNA sythetase
13
Q
D arm of tRNA
A
lots of dihydrouracil residues
14
Q
T arm of tRNA
A
contains sequence necessary for binding to ribosomes - thymidine, pseudouridine, cytidine
15
Q
RNA containing thymidine
A
tRNA
16
Q
5’ end of tRNA
A
terminal phosphate
17
Q
larger protein, altered fx, retained immune reactivity - type of mt?
A
spice site mutation
18
Q
vitamin tx for measles
A
vit A
19
Q
Dermatitis, Diarrhea, ….
A
Niacin def
20
Q
Child with ataxia, pruritic skin lesions, loose stools + netural aromatic aas in urine
A
Hartnup:
imparied instinal and renal absorption of tryptophan
tryptophan:
niacin, serotonin, melatonin
21
Q
precursor of the NAD+ coenzyme
A
tryptophan
22
Q
skin blisters, increased plasma porphyrins… enzyme?
A
uroporphyrinogen decarboxylase
23
Q
human enzyme that has reverse transciptase
A
telomerase
24
Q
subperiosteal hemotomas
A
scurvy - ascorbic acid/vit C def
25
cytoplasmic p bodies
role in mRNA translation regulation and mRNA degredation
26
snRNPs participate in function of...
spliceosomes
27
pyruvate dehdrogenase: which aa can you supplement safetly; why
lycine and leucine
| - exclusively ketogenic and will not increase blood lactate levels
28
pyruvate dyhdrogenase: fx
pyruvate --> acetyl CoA
29
pyruvate dehdrogenase: cofactors
```
"TLC For Nobody"
Thyamine pyrophsophatase (B1)
Lipoic Acid
Co-enzyme A (B5)
FAD (B2)
NAD+ (B3)
```
30
What uses the same cofactors as PDH
alpha KG dehydrogenase
31
What B vitamins are cofactors for PDH and alpha-KG dehydrogenase
B1 (thiamine)
B2 (riboflavin)
B3 (niacin)
B5 (panthenoic acid/panthenate)
32
arsenic poisoning MOA/symp
blocks lipoic acid (cofactor of PDH and alpha-KG dehrogenase)
Sx:
garlic breath
rice water stool
vomiting
33
alpha-KG dehdrogenase fx
alpha-kg --> succinyl-CoA (TCA cylcle)
34
PDH complex def symp
- build up of pyruvate gets shunted to lactate (via LDH) --> lactic acidosis
- neurologic defects
- high levels of serum alanine starting in infancy
35
PDH def congenital (geneics)
X-linked
36
PDH def tx
increase ketogenic nutirents (high fat content or increased lysine and leucine)
37
What are the 2 fates of pyruvate in the cytosol? (and via which enzymes/cofactors)
Cytosol:
Alanine
- via alanine aminotransferase (B6)
- carries amino groups to the liver from muscle
- Cahill cycle
Lactate
- via LDH (B3)
- end step of anaerobic glycolysis
- Cori cycle
38
What are the 2 fates of pyruvate in the mitochondria (and via which enzymes/cofactors)
Mitochondria:
Oxaloacetate
- via pyruvate carboxylase (biotin)
- addition of CO2 and ATP
- can replenish TCA cycle or used in gluconeogenesis
Acetyl CoA
- via PDH (B1, B2, B3, B5, lipoic acid)
- transition from glycolisis to TCA cyle
39
where is anaerobic glycolysis major pathway (6)
```
RBCs
Leukocytes
Kidney medulla
Lens
Cornea
Testes
```
40
Potassium channel position when increased glucose (...)
CLOSED
- in response to increased ATP (from glucose met)
- -> depolarization --> open Ca channels--> exocytosis)
41
B6 deficiency: impairments in what conversion of pyruvate
pyruvate --> oxaloacetate
42
Biotin (B6) - roles
- CO2 carrier on carboxylase (e.g. pyruvatec carboxylase)
- decarboxylase rxs
- glycogen phosphorylase
- transamination (ALT, AST)
- conversion of aa precursors
(histamine, serotonin, epi, NE, DA, GABA)
- synthesis of cystathionine, heme, niacin
43
Enzyme directly responsible for early lens opacities
Aldose reductase
44
insulin receptor cascade
tyrosine kinase -->
phosphorylation of insulin receptor substates-->
activation of protein phosphatase -->
(1) dephosphorylates glycogen synthase -->
(glycogen synthase activated) -->
increase glycogen synthesis
(2) dephosphorylates F-1,6-biphosphatase -->
(inactivated) -->
inhibids gluconeogenesis
45
JAK protein kinase
second messenger system for peptide hormones such as some cytokines in JAK-STAT pathway (signal transducers and activators of transcription)
has tyrosine kinase activity; receptor does NOT have INTRINSIC tyrosine-kinase activity - i.e. - tyrosine-kinase ASSOCIATED receptor
46
Fuels post-absorbative
| brain and muscles/other tissues
All: glucose
47
When does gluconeogenesis begin?
When is it fully active?
(hrs after last meal)
4-6 hrs - begins
| 10-18 hrs - fully active (glycogen depleted)
48
Glycogen depleted (hrs)
10-18 hrs
49
Fuel 24 hrs after last meal
Brain:
glucose
Muscles/other tissues:
FA
(some glucose)
50
Fuel 48 hrs after last meal
Brain:
glucose
(some ketone bodies)
Muscles/other tissues:
FA
(some ketone bodies)
51
Fuel 5 days after last meal (prolonged starvation)
Brain:
ketone bodies
Muscles/other tissues:
FA
(some ketone bodies and a little glucose)
52
Overnight fast-
| what percentage of energy comes from glucose and from ketone bodies
Overnight:
90% glucose (2/3 gycogen, 1/3 gluconeogenesis)
5% ketone bodies
53
3 day fast-
| what percentage of energy comes from glucose and from ketone bodies
3 day fast:
60% ketone bodies (1/2 beta-hydroxybutyrate, 1/2 acetoacetate)
40% glucose (gluconeogen)
54
What metabolic scenario favors synth of ketone bodies
production of acetyl CoA from B-oxidation
exceeds
oxidative capacity of the TCA cycle
55
What cells cannot use ketone bodies
RBCs
| - can only use glucose
56
Primary energy source in a pt that has not eaten in two days
FAs
57
Rate limiting step of ketone body synth
HMG CoA Synthase
58
Etoh --> hypoglycemia
- etoh metab increases NADH
- pyruvate --> lactate and oxaloacetate --> malate used to regenerate NAD+
- depleted substates for gluconeogenesis
59
insulin receptor structure
tetramer:
2 alpha - extracellular binding
2 beta - intracellular signalling (contain tyrosine kinase domains)
60
TNF alpha insulin resistance mech
TNF alpha activates serine kinases -->
1) phosphorylate IRS-1 serine residues -->
inhibits IRS-1 tyrosine phosphorylation by insulin
2) phosphorylates serine residues in beta subunit of insulin
note: phosphorylation of threonine resides has similar effects
61
What increases insulin resistance via phosphorylation of serine or threonine residues
```
TNF-alpha
catecholamines
glucocorticoids
glucagon
(maybe intracellular FFAs)
```
62
NE --> Epi
-PNMT
(phenylethanolamine-N-methyltransferase)
- PNMT transcription increased by CORTISOL
- occurs mostly in adrenal medulla (unlike DA and NE - produced in cetral and peripheral nervous system)
63
enzyme tyrosine --> DOPA
tyrosine hydroxylase
64
enzyme DOPA --> dopamine
dopamine decarboxylase
65
enzyme dopamine --> NE
dopamine beta-hydroxylase
66
enzyme NE --> Epi
PNMT
| pheylethanolamine-N-methyltransferase
67
Use receptor tyrosine kinase?
Signalling pathway
```
Growth FACTOR receptors:
- EGF
- PDGF
- FGF
(etc)
```
MAP-kinase
Ras
68
Use tyrosine-kinase associated receptor
Signalling pathway
```
Receptors for:
cytokines
GH
PRL
IL-2
```
JAK/STAT
69
Liver enzyme - TG breakdown products --> glucose precursor
glycerol kinase
glycerol --> glyceral 3-phosphate
(glycerol 3-phosphate --> DHAP --> (1) glycolysis or (2) gluconeogen
70
Rate limiting step of HMP shunt (pentose phosphate pathway)
Glucose-6-P dehydrogenase
71
Enzyme in oxidative (irreversible) phase of HMP shunt
G6PD
72
Enzyme in nonoxidative (rervserible) phase of HMP shunt
Phosphopentose isomerase, transketolases
73
Sites of HMP shunt
```
CYTOPLASM of
RBCs and sites of fatty acid or steroid synth:
- lactating mammary glands
- liver
- adrenal cortex
```
74
Purpose of HMP shunt
- provide source of NADPH from G6P
| - yields ribose for nucleotide sythesis and glycolitic intermediates
75
NADPH uses
- synth of FA and cholesterol
- GENERATION of oxygen free rad
- PRODECTION of RBCs from oxygen free rad
- cytochrome p450
76
hormones that act through g-protein receptors
```
glucagon
TSH
PTH
LH
FSH
(all Gs (?) - work through adenylate cylcase--> cAMP --> protein kinase A)
```
77
alpha subunit of g-protein receptor's response to stimulation
release of GDP;
binding of GTP -->
dissociation of alpha subunit
78
rate limiting step in FA degredation and where is it located
CAT - 1
(carnitine acyl transferase 1)
(aka carnitine palmitoyl transferase 1)
cytoplasm of mitochondria?
79
What is the shuttle in FA degredation
carnitine
80
What is the shuttle in FA synth
citrate
81
What is the rate limiting step in FA synth
acetyl- CoA carboxylase
82
Nonpolar, hydrophobic amino acids
```
valine
alanine
isoleucine
methionine
phenylalanine
```
83
alpha helix of 20 aa
transmembrane region
84
aldolase B def
| - what should be removed from diet
fructose
| sucrose (fructose+glucose)
85
aldolase B def - mechanism
phosphate trapping in fructose 6 phosphate
86
fructose --> frucotse 1-P
fructokinase
87
fructose 1-P --> glyceraldehyde or DHAP
aldolase B
88
bypasses rate limiting step of glycolysis (PFK)
fructose
89
DHAP --> F-1,6-BP
and
Glyceraldehyde-3-P --> F-1.6-BP
Muscle:
Aldolase A
Liver:
Aldolase B
90
Aldolase B def
Fructose intolerance
91
Fructokinase def
Essential fructosuria
92
positive gibs free energy favors...
reactants/substrates
93
cortisol receptor location
cytosol
94
Mcardle disease enzyme
myophosphorylase (muscle glycogen phosphorylase)
95
Cori disease enzyme
Debranching enzyme (1-6 glucosidase)
| maybe debranching enzyme transferase
96
von Gierke disease enzyme
Glucose-6-phosphatase
97
Pompe disease enzyme
Acid alpha gucosidase
| acid maltase
98
mild hyperglycemia exacerbated by pregnancy (enzyme inactive)
glucokinase:
| glucose sensor within pancreatic beta cells
99
acetoacetyl-CoA --> 3-hydroxy-3-methylglutaryl CoA
pathway
synthesis of cholesteral and ketone bodies
100
vomiting, lethargy, failure to thrive soon after beginning breastfeeding
Classic galactosemia:
| galactose-1-phosphate uridyl transferase
101
infant not tracking objects; lack of social smile
| enzyme def
galactokinase deficiency
102
Thyroid hormone receptor
nuclear receptor
103
Retinoids receptor location
nucelar receptor
104
PPAR receptor location
| peroxisomal proliferating activated receptors
nucleus
105
FA receptor locations
nucleus
106
Pyruvate carboxylase
location
pathway
action
mitochondria
gluconeogenesis
pyruvate --> oxaloacetate
107
Ornithine transcarbamoylase
location
pathway
action
mitochondria
urea cycle
ornithine + carbamoyl phosphate --> citrulline
108
succinate dehdrogenase
location
pathway
action
mitochondria
TCA cycle
succinate--> fumarate
109
3-hydroxy-3mthyglutaryl-CoA lyase
location
pathway
action
(HMG CoA lyase)
mitochondria
ketogenesis from HMG CoA
(HMG CoA from degradation of leucine or synth from HMG CoA synthase)
110
removal of pitutitary --> decreased epi
what enzyme act is decreased?
Pheylethanolamine-N-methyltransferase (PNMT)
111
allosteric activator of pyruvate carboxylase
Acetyl CoA
| increases gluconeogenesis
112
sorbitol end product
fructose
113
glucose --> sorbitol
aldose reductase
| NADPH --> NADP+
114
sorbitol --> fructose
sorbitol dehydrogenase
| NAD+ --> NADH
115
cells with particularly active polyol pathway
(glucose-sorbitol-fructose)
seminal vesicles
- sperm use fructose as primary energy source
116
cells with less polyol pathway ability
(glucose-sorbitol-fructose)
Have less sorbitol dehydrogenase:
- retina
- renal papilla
- Schwann cells
117
pH above pKa
no H
- acids neg (eg COO- )
- bases neutral
118
pH below pKa
H
- acids neutral
- bases positive (eg NH3+)
119
In fructokinase deficiency - what enzyme compensates to in fructose metabolism
hexokinase
| fructose --> fructose 6-phosphate.... glycolysis
120
defect in lipoic acid results in...
| 2
- lactic acidosis (PDH def)
- Maple Syrup Urine disease (branced-chain ketoacid DH)
(also alpha-KG DH def)
121
biologically active form of pantothenic acid
coenzyme A
122
TCA cycle step that requires B5
oxaloacetate --> citrate
| B5 = coenzyme A
123
CoA important in synthesis of...
```
Vit A
Vit D
cholesterol
steroids
heme A
FAs
AAs
proteins
```
124
How is pantothenic acid activated
- actively transported into cell
| - ATP dependent phosphorylations --> coA
125
Niacin dependent steps in TCA cycle
(NADH steps)
isocitrate --> alpha-KG
alpha KG --> succinyl CoA
*requires many cofactors
malate --> oxaloacetate
126
Pompe disease muscle bx
enlarged lysosomes containing periodic acid-Schiff (PAS) + material
127
infant w/ cardiomegaly, macroglossia, profound muscular hypotonia
Acid maltase (alpha-glucosidase) deficieny
| Pompe
128
accumulation of glycogen with abnormally short outer chains
debranching enzyme deficiency
| Cori disease
129
GLUT 1
RBCs
BBB
basal glucose transport
130
GLUT 2
hepatocytes
beta cells of pancreas
renal tubular cells
small intestine
regulation of insulin release
131
GLUT 3
placenta
| neurons
132
GLUT 4
skeletal muscle
adipocytes
insulin mediated uptake
133
GLUT 5
spermatocytes
GI tract
fructose transport
134
riboflavin dependent step in TCA cycle
Coenzyme of succinate dehdrogenase:
| succinate --> fumarate
135
glossitis
cheilitis
corneal neovascularization
ribovlavin (B2) deficiency
136
liver cells with HIGH concentration of F-2,6-BP will have LOW rate of conversion of...
alanine --> glucose
137
Increases F6P --> F-2,6P
insulin
138
inhibition of lactate dehydrogenase would halt glycolysis due to depletion of ...
NAD+
139
what step of glycolysis regenerates NAD+ from NADH
pyruvate--> lactate
140
"red neurons"
| description and timeframe
red neurons: sign of IRREVERSIBLE neuronal injury
12-48 hrs after injury
eiosinophilic cytoplasm
pyknotic nuclei
loss of nissl substance
(will fragment and be phagocytized by macrophages)
141
Micorosopic/Macroscopic changes in ischemic brain tissue
| timeframe, description
12-24 hrs
Micro: red neurons
1-4 days
Micro: necrosis and neutrophils
3-5 days
Micro: macrophages
1-2 wks
Micro: reactive gliosis, vascular proliferation around necrotic area
Macro: liquifactive necrosis - well demarcated soft area (1 wk - 1 month)
>2 wks
Micro: glial scar
Macro: cystic area surrounded by gliosis (> 1mo)
142
hepcidin -->
hepcidin-->
decreased ferroportin expression on basolateral surface of enterocytes--->
decreased iron secretion into circulation
143
MCC of primary hemochromatosis
mt in HFE protein
HFE interacts with transferrin receptor to increase endocytosis of the iron-transferrin complex
this iron is added to the regulatory pool to control
mt= sensing falsley low iron levels
144
holosytolic
apex
radiates to axila
mitral regurg
145
best indicator of severity of mitral regurg
presence of S3
146
best indicator of severity for mitral stenosis
S2 to opening snap interval
| shorter worse - ?
147
thin septate hyphae
(with acute angles)
| Aspergillus
148
Giardia
| immune defect
IgA
149
Sitting up from supine
| muscles
- external abd obliques
- rectus abdominus
- hip flexors (mainly iliospsoas)
- -> psoas major/minor
- -> iliacus
150
superior laryngeal nerve - external branch
| (innervation)
cricothyroid muscle
151
superior laryngeal nerve - internal branch (innervation)
sensory innervation above vocal cords
152
reccurant laryngeal nerve
| innervation
all laryngeal muscles except cricothyroid
sensory innervation below the vocal cords
153
nerve at risk by superior thyroid artery and vein
exterior branch of superior layrngeal
154
histo of Reye
- microvesicular steatosis of hepatocytes
- NO inflammation
- cerebral edema
155
Enzyme in galactose metabolism impaired in secondary lactose intolerance
Beta-galactosidase
Lactose (galactosyl-beta-1,4-glucose) --> Galactose
156
fates of galactose
G1P --> G6P --> pyruvate
| UDP-galactose --> Lactose
e.g. in milk production
157
where does mannose enter glycolysis
mannose --> mannose-6P --> fructose-6P
158
where does fructose enter glycolysis
```
fructose
---- (fructokinase)-->
fructose-1P
----(Aldolase B)--> glyceraldehyde (and DHAP)
-----(Triokinase)--->
glyceraldehyde-3-phosphate
----(Aldolase A or B)-->
fructose-1,6-BP
```
**Enters after regulation by PFK1
159
mushroom toxin
(amatoxins)
inhibit RNA polymerase II
--> halt mRNA synthesis
160
Euk RNA polymerase i
ribosomal RNA
161
Euk RNA polymerase II
messenger RNA
162
Euk RNA polymerase III
transfer RNA
163
ricin toxin
| from castor oil plant ricinus
inhibits protein syth by cleaving the rRNA component of the 60S subunit
164
Leptin sites of action
- acuate nuclus of hypothal to:
- INHIBIT prod of NPY
- STIM prod of alpha-MSH
165
lac operon - produces...
- beta-galactosidase
(lactose --> glucose + galactose)
- permease
(increases permeability to lactose)
(an unnecessary one - transacetylase)
166
lac operon - repressor bound state
absent lactose
| lactose binds to and releases repressor
167
lac operon - state with excess glucose and excess lactose
nothing bound
- repressor unbound due to lactose
- CAP (activator) not bound due to excess glucose --> decreasing activity of adenylate cyclase --> decrease intracellular cAMP
168
lac operon - control of catabolite activator protein (CAP)
- inhibited by low intracellular cAMP
169
Pigmented gallstones
- enzyme
- risks
infx of biliary tract -->
release of beta-glucuronidase from injured hepatocytes and bacteria--->
hydrolysis of bilirubin glucuronides--->
increase unconj bilirubin in bile
```
risks:
biliary infx with
E coli
Ascaris
Opisthrchis (liver fluke)
```
170
common trigger for hepatic encephalopathy
GI bleeding
| increase in ammonia and nitrogen absorption by the gut
171
cells in brain affected by acute rise in ammoninia
astrocytes
| neurons
172
ammonia toxicity results from depletions of... (in the brain)
(2)
GLUTAMATE
- increased conversion of glutamate --> glutamine by glutamine synthetase in astrocytes (excess glutamine --> astrocyte swelling and dysfx)
ALPHA-KETOGLUTARATE
- NH4 can detoxified to glutamate with alpha-KG via glutamate dehydrogenase --> depletes alpha-KG --> impairs energy metabolism (TCA cyle)
173
Lynch syndrome
| genetics
AD
| abnormal nucleotide mismatch repair
174
cofactor in synthesis of delta-aminolevulinic acid
pyridoxal phosphate
succinyl-CoA + glycine (w/ pyridoxal phosphate)---> ALA
175
ribosomal subunit fx:
| - 23S
in 50s ribosome
| - facilitate peptide bond formation (peptidyltransferase)
176
ribosomal subunit fx
| - 16S
in 30s ribosome
- contains sequence complementary to the "Shine Dalgamo" sequence on mRNA
- binding of these complementary sequences necessary for initiation of protein translation
177
Shine Dalgamo sequence
in all prokaryotic mRNA
- located ~10bp up from the AUG start codon
- allow for binding to 16S subunit on 30S ribosome
178
ApoA-1
LCAT activation (cholesterol esterification)
179
ApoB-48
chylomicron assembly and secretion by the instestine
180
ApoB-100
LDL particle uptake by extrahepatic cells
181
ApoC-II
lipoprotein lipase activation
182
ApoE-3 and 4
VLDL and chylomicron remnant uptake by liver cells
183
Kozak consensus sequence
Eukaryotic mRNA
upstream from AUG (methione start)
initiator for translation (i.e. mRNA binding to ribosomes)
* a purine (G or A) positioned 3 bases upstream from the AUG appears to be a key factor
* mt a/w thalassemia intermedia
184
Beta thalasemia mt causes...
defective transcription, processing, and translation of beta-globin mRNA
185
Target cell ddx
"THAL" (or "HALT"
- Thallasemia
- HbC disease
- Asplenia
- Liver disease
186
HbC and HbS electrophoresis
HbC will not travel as far as either normal or HbS;
HbS will not travel as far as normal
HbS
neg charged glutamate --> nonpolar valine (decreased neg charge)
HbS
neg charged glutamate --> positively charged lysine (even less neg charge)
187
cyanide poisoning antitode mech
Nitrites:
hemoglobin (Fe2+)--> methemoglobin (Fe3+)
methemoglobin binds CN more tightly --> keeps it sequestered in blood and away from mitochondrial enzymes
188
activators of ALA synthase
Etoh
Barbiturates (think of w/anxiety)
Hypoxia
189
Repressors of ALA synthase
heme
| glucose
190
Acute Intermittent Porphyria
| symptoms
```
5 P's:
Painful abdomen
Port wine urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs*
```
```
Barbituates
Seizure drugs
Rifampin
Metoclopromide
Etoh
griseofulvin
phenytoin
```
(also stavation)
191
Acute intermittent porphyria tx
heme and glucose --> block ALA synthase
192
Enzyme- acute intermittent porphyria
Porphobilinogen deaminase
193
Enzyme - porphyria cutanea tarda
uroporphyrinogen decarboxylase
194
Enzyme - lead poisoning
ALA dehydratase
| Ferrochelatase
195
triggers for sickle cell aggregation
hypoxia
low pH
high 2,3DPG
196
heme --> biliverdin
| enzyme
Heme oxygenase
197
glutamate residue carboxylation in liver
| vitamin
K
| essential for some clotting factor production
198
Active or passive:
1) liver uptake of unconj bili
2) liver excretion of conj bili
1) passive uptake
2) active secretion into bile canniculi*
passive diffusion via baolateral OATP allows conj bili to leak into blood stream
199
Crigler Najal
| enzyme
UDP-glucuronyl transferase
- absent
(conjugation of bili)
200
Gilbert syndrome
| enzyme
UDP-glucuronyl transferase
- low
(conj of bili)
201
Defect in secretion of bile
Dubin- Johnson
| Rotor
202
Stop codons
UGA
UAA
UAG
"U Go Away"
"U Are Away"
"U Are Gone"
203
spoon nails + dysphagia
Fe deficiency
204
Anemia:
PO2
% Saturation
O2 content
pO2: normal
sat: normal
O2 content: low
205
```
after beginning chemo:
hyperphosphatemia
hypocalcemia
hyperkalemia
hyperuricmia
```
dx and tx
tumor lysis syndrome
tx (prevention):
hydration + hypouricemic agents (allopurinol or rasburicase)
206
Rasburicase
| MOA
recombinant urate oxidase
uric acid --> allantoin (more soluble than uric acid)
207
chemo --> cardiotoxicity
| drug and prevention
Drug:
doxurubicin
daunorubicin
Prevent:
dexrazone
*trastuzumam (herceptin) also causes cardiotoxicity
208
chemo --> myelosuppression
| 2
Drug:
methotrexate
Prevent:
leukovorin (folinic acid)
Drug:
5-FU
Prevent:
uridine
209
chemo --> hemorrhagic cystitis
Drug: cyclophosphamide
Prevent:
mesna
210
Give dexrazene with ___ to prevent _____
with: doxurubincin/daunorubicin
to prevent:
cardiotxicity
211
Give leukovorin with ___ to prevent_____
with:
methotrexate
to prevent:
myelosuppression
212
Give mesna with ___ to prevent ____
with:
cyclophosphamide
to prevent: hemorrhagic cystitis
213
Give uridine with ____ to prevent ____
with:
5-FU
to prevent:
myelosuppression
214
- exertional dyspnea
- pneumonia (--> life threatening acute chest syndrome)
- recurrent abdominal and bone pain
Sickle cell
glutamic acid --> valine
215
G6PD action
GDPD --> 6-phosphogluconate
*rate limiting step in HMG/pentose phosphate shunt
216
G6PD deficiency genetics
X-linked
217
G6PD necessary for:
HMP (pentose phosphate) shunt:
- produce NADPH
- produce ribulose-5-phosphate
218
mt in JAK2
| 3 blood d/o
-essential thrombocytosis
(hemorrhagic and thrombotic symptoms)
-polycythemia vera
(pruritis, splenomegaly, thrombotic cx)
- primary myelofibrosis
(severe fatigue, splenomegaly often causing early satiety, hepatomegaly, anemia, bone marrow fibrosis)
219
Primary myelofibrosis smear
teardrop (dacrocytes)
| nucleated RBCs
220
bisphosphoglycerate mutase
1,3BPG --> 2,3BPG
*consumes energy that would have otherwise been used to produce energy in the form of ATP
(alternate glycolytic pathway)
221
pyruvate kinase deficiency
```
[phosphoenolpyruvate --> pyrvate)
def --> hemolytic anemia due to failure of glycolysis
```
--> splenic hypertrophy due to increased work of removing deformed erythrocytes
222
Haldane effect
binding of O2 drives release of H+ and CO2 from hemeoglobin
223
Bohr effect
high CO2 and H+ facilitate O2 unloading from Hb
224
xeroderma pigmentosum
| enzyme; genetics
AR
| endonuclease - nucleotide excision repair enzyme
UV-specific endonuclease
225
Fructose -6P --> ribose
| enzymes- 2
transaldolase
transketolase
(non-ox/reversible reactions of the HMP shunt)
*all cells
226
radiation (tx) mech
1) DNA double strand breaks
| 2) formation of free radicals (reactive oxygen species from ionization of water)
227
RBCs unable to synth heme b/c of lack of...
mitochondria
| necessary for first and final three steps
228
mTOR pathway
growth factor binds to rec tyrosine kinase
- -> activate phosphoinositide 3-kinase (PI3K)
- -> phospholylates PIP2 to PIP3 (in plasma membrane)
- -> activate protein kinase B (Akt) - a serine/threonin specific kinase
- ->activates mTOR
- ->mTOR translocates to nucleus
- -> induce genes for survival, anti-apoptosis, angiogenesis
*inhibitied by PTEN, a tumor suppressor proetin that removes phosphate from PIP3
229
Why is HCV genetically unstable
- it's RNA polymerase lacks proofreading 3'-->5' exonuclease
| - envelope glycoprotein contains a hypervariable region prone to mt
230
Alkaptonuria
AR
homogentisate oxide def
- step in tyrosine --> fumarate
- dark connective tissue
- brown sclerae
- urine turns black on prolonged exposure to air
may have debilitating arthralgias (homogentisic acid toxic to cartilage)
231
increased glycogenolysis in muscles (mech)
increased calcium in cytosol
- ->allosterically activates phosphorylase kinase
- -> phosphorylates (activates) muscle phosphorylase
- -> ---> glycogen breakdown
232
additions or deletions of a number of base not in a multiple of 3
framshift
233
MC cystic fibrosis mt mech
codon deletion of phenylalanine
234
Antibodies w/ high specificity for rheumatoid arthritis
anti-citrulinated peptide
| anti-CCP
235
main amino acids in elastin
glycine
alanine
valine
(all non-polar)
also contains proline and lysine but most are not hydroxylated (unlike collagen)
236
what accounts for elastin's resilance
extensive desmosine crosslinking
(interchain crosslinks involving 4 different lysines on 4 elastin chains)
extracellualar lysyl hydroxylase does crosslinking
237
```
severe abdominal pain
hypotension
hyperventilate
met acidosis
increased AG
high plasma lactate
```
what enzyme has low activity
pyruvate dehydrogenase
(oxidative phosphorylation pathway)
(this is hypoxia-induced lactic acidosis)
238
what about the desired gene do you need to know to do pcr
the nucleotide sequence of the regions flanking the target DNA
239
fibrillin
major component of the microfibrils that form a sheath around elastin fibers
acts as an extracellular scaffold for deposition of elastin extruded from connective tissue cells
abundant in blood vessels, periosteum, and suspensory ligaments of the lens
240
glycoprotein from viral sythesis that forms spheres and tubules and poorly correlates with viral replication
an envelope component of HBV
(HBsAg)
often made in large excess
241
location of collagen hydroxylation of proline/lysine
| requires vit C
RER
242
most abundant protein in the human body
collagen
243
most abundant amino acid in collagen molecule
glycine
| at LEAST every 3rd amino acid
244
defects in ubiquitin-proteasome system can lead to what neurodegen d/os
Parkinson
| Alzheimer
245
PKU tx with tyrosine --> normal serum phenylalanine but elevated PRL
what enzyme is def
Dihydrobiopterin reductase
246
Tetrahydrobipterin (BH4) cofactor in...
phenylalanine --> tyrosine
tyrosine--->DOPA
synth of serotonin
synth of NO
247
Alanine --> ?
Aspartate --> ?
via alpha-KG transamination
alanine --> pyruvate
aspartate --> oxaloacetate
248
cofactor for transamination
B6
249
major transporter of nitrogen to the liver for disposal
alanine
250
what carries nitrogen to the kidneys from most tissues
glutamine
glutamine
---(glutaminase)--->
glutamate + NH3
251
Vit A tox
intracranial htn
skin changes
hepatosplenomegaly
hyperlipidemia
acute:
n/v
vertigo
blurred vision
252
N-acetylglutamate
| - activator of _____ in NH3 exretion
carbomoyl phosphate synthase 1
| CO2 + NH3 --> carbomoyl phssphate
entry into the urea cycle
253
amino group of what aa directly provides N for the urea cycle
aspartate
254
megoloblastic anemia
neuro abnl
growth retardation
orotic acid in urine
orotic aciduria (AR):
defect in UMP synthase (pyrimidine synth pathway)
unable to convert orotic acid --> UMP
supplement with uridine monophosphate
NB: NORMAL ammonia (vs ornthine transcarbamylase def)
255
ornithine transcarbamylase def
XR
defect in urea cycle
- increased orotic acid in blood and urine
- HIGH ammonia in blood
- low BUN
- NO megaloblastic anemia
```
tx:
decrease protein
phenylbuterate
benzoate
biotin
```
256
enzymes that use B1
pyruvate dehydrogenase
alpha-KG dehydrogenase
transketolase
257
foamy histiocytes
Niemann-Pick
| sphyngomyelin accumulates in histiocytes
258
metabolism of very long chain fatty acids or fatty acids with branch points at odd numbers
peroxisomes
- VLCFA --> special form of beta ox
- branched chain (e.g. phytanic acid) --> alpha ox
259
peroxisome defects lead to
neuro deficits from improper CNS myelination
260
young
spastic paresis of LE and choreoathetoid movements
high arginine
enzyme
arginase
| last step in urea cycle
261
phenylalanine derivatives
phenylalanine --->
--[BH4]-->tyrosine
( also tyrosine---> thyroxine)
--[BH4]-->Dopa
( also Dopa--->Melanin)
- -[B6]-> Dopamine
- -[vit C]-> NE
- -[SAM]-> Epi
262
Tryptophan derivatives
tryptophan
--[B6]--> Niacin
tyrptophan
- -[B6, BH4]--> serotonin
- --> melatonin
263
Histadine derivatives
histadine
| --[B6]--> histamine
264
Glycine derivatives
glycine
- -[B6]--> porphyrin
- --> heme
265
Glutamate dervivatives
glutamate
--[B6]--> GABA
glutamate
---> glutathione
266
Arginine derivatives
arginine
---> creatine
arginine
---> urea
argininine
--[BH4]--> Nitric Oxide
267
transamination reaction (vit)
B6
| pyridoxal phosphate
268
```
met acidosis
large AG
ketosis
hypoglycemia
high methylmalonic acid
```
deficient reaction
Isomerization
methylmalonyl CoA --> Succinyl CoA
(this is methylmalonic acidemia)
269
what amino acids should be avoided in Maple Syrup Urine Disease
(branched chain)
leucine
isoleucine
valine
270
principal stabilizing force for secondary structure of proteins
H bonds
271
cofactors for branched chain alpha-ketoacid dehydrogenases
(like PDH and alpha-KG DH)
```
TLC For Nobody
thiamine
lipoic acid
coenzyme A
FAD
NAD
```
272
Maple Syrup Urine Disease enzyme
branched chain alpha-ketoacid-dehydrogenase
273
Propionyl CoA
| comes from....
```
- AAs:
Threonine
Methionine
Valine
Isoleucine
```
- odd-numbered FAs
- cholesterol side chains
