QB - BIOCHEM Flashcards
1
Q
Folate deficiency
A
dUMP –> dTMP via thymidylate synthetase
dTMP needed for supply of 4 nucleotide precursors of DNA replication
megaloblastosis & erythroid precursor cell apoptosis
2
Q
Cell surface markers:
a. CD4, CD8
b. CD7
c. CD14
d. CD20
A
CD4 = T Helper CD8 = Cytotoxic T cell CD14 = monocyte-macrophage lineage (usually identifies granulomas like in TB) CD20 = B cell (Rituximab targets CD-20)
3
Q
Anemia due to hemolysis (DRUG causes)
A
G6PD deficiency
Pyruvate kinase deficiency
Sulfonamides (SMX)
Anti-malarials
4
Q
Second messenger pathways of: Insulin
A
Insulin = acts on cell surface receptor TYROSINE KINASE
5
Q
Second messenger pathways of: GH
A
GH = JAK –> stimulates tyrosine kinase –> STAT activity –> increases gluconeogenesis (JAK/STAT pathway)
6
Q
Second messenger pathways of: Catecholamines
A
Catecholamines = G-protein coupled, membrane bound receptors –> increase cAMP by adenylyl cyclases, phospholipase C –> second messenger systems = inositol 1,4,5-triphosphate (IP3) & diacylglycerol (DAG)
7
Q
Second messenger pathways of: Glucagon
A
Glucagon = same as catecholamines
Catecholamines = G-protein coupled, membrane bound receptors –> increase cAMP by adenylyl cyclases, phospholipase C –> second messenger systems = inositol 1,4,5-triphosphate & diacylglycerol (DAG)
8
Q
Second messenger pathways of: Cortisol
A
Cortisol = cortisol receptors in CYTOPLASM –> heat shock proteins released, receptors homodimerize –> translocate to nucleus to increase transcription of enzymes involved in gluconeogenesis
9
Q
Rb gene
A
regulation of cell cycle
mutation in Rb –> can’t arrest cell cycle in G1 phase
Retinoblastoma
Osteosarcoma
10
Q
Ras protein
A
Codes G-protein that regulates signal transduction – activates MAP kinase pathway
Unregulated cell division, inhibited apoptosis, decreased cell adhesion (cells migrate –> malignancy/metastasis!)
11
Q
S-100 proteins
A
Ca2+ binding proteins similar to calmodulin structure
Important for intracellular protein phosphorylation & cell growth/differentiation
S-100 marker for neural crest derivation (melanocytes & Schwann cells) and Langerhans cells
12
Q
DNA mismatch repair
A
Hereditary colorectal cancer/Lynch syndrome
13
Q
Peptide hormones
A
PTH, ACTH, glucagon, gonadotropins
7 transmembrane regions spanning plasma membrane; one amino-terminal domain (hormone binding) and one carboxy-terminal domain
Extracellular amino-terminal binds hormones –> cytoplasmic carboxy-terminal activates G PROTEIN –> second messenger activation via cAMP/adenylyl cyclase
OR via phospholipase C –> more second messengers (inositol 1,4,5-triphosphate) and diacylglycerol (DAG)
14
Q
Steroid hormone receptors
A
Located in cytoplasm
Glucocorticoids (cortisol)
Mineralcorticoids (aldosterone)
Estrogens
15
Q
Thyroid hormone receptors
A
Located in nucleus
Also, fatty acids, retinoids, peroxisomal proliferating activated receptors (PPAR)
16
Q
TNF-alpha; function? Drugs that inhibit TNF-alpha? What type of hypersensitivity is it associated with?
A
Produced by macrophages + mast cells
Signals apoptosis in tumor cells
Activation of inflammatory cells
Infliximab, Etanercept (TNF-alpha inhibitors):
binds to TNF-alpha and inhibits it from inducing inflammation
TNF elevated in type IV hypersensitivity
17
Q
GLUT-4
A
Skeletal muscles and adipocytes
18
Q
Glucocorticoids (anabolic effects)
A
Stimulate liver gluconeogenesis
Increases PEP carboxykinase (OAA –> PEP) & glucose-6-phosphatase (G6P –> glucose)
Increase glycogen synthetase –> increase glycogenesis
19
Q
Glucocorticoids (catabolic effects)
A
Antagonize insulin in muscles/adipose –> muscle breakdown –> increase BUN
Inhibit fibroblast proliferation/collagen formation –> purple striae & impaired wound healing (skin thinning)
Immunosupressant –> decrease Th cells; decrease eosinophils; increase neutrophil (due to demargination from blood vessels)
Decrease bone mass –> osteoporosis
20
Q
How does administration of glucocorticoids result in hyperglycemia?
A
increase liver protein synthesis (gluconeogenesis and glycogenesis) + antagonism of insulin
21
Q
Serine phosphorylation
A
Causes insulin resistance
FREE FATTY ACIDS thought to cause insulin resistance (obesity and diabetes go hand in hand)
Mechanism by TNF-alpha, glucagon, glucocorticoids
22
Q
B-hydroxybutyrate
A
Marker of insulin deficiency (type I diabetes)
23
Q
Polyol pathway
A
Glucose — aldose reductase –> Sorbitol
Sorbitol — sorbitol dehydrogenase –> Fructose
buildup of sorbitol in lens from longstanding hyperglycemia = cataracts
24
Q
Hep B blood serology
A
HBs - infection HBc - core (infection) HBe - transmissability Anti-HBs: immunity/prior infection Anti-HBc - active infection (IgM), prior infection (IgG) -- positive in the window period Anti-HBe - lowers transmission
25
Homocystinuria; enzyme deficiency? What vitamin should be given?
Cystathionine synthetase deficiency
- thromboembolism of large/small vessels - esp. in brain
- Marfan skeletal symptoms
- give PYRIDOXINE (B6)
26
Tyrosine
Precursor for catecholamines: dopamine, EPI, NE
27
Thiamine
B1
| Causes dry beriberi, wet beriberi, Wernicke-Korsakoff (in alcoholics)
28
Hydroxylation of proline
```
Formation of collagen
Prolyl hydroxylase (Vitamin C needed)
```
Scurvy = deficiency in Vitamin C = poor connective tissue strength
29
Formation of serotonin
Hydroxylation + decarboxylation of Trytophan
Tryptophan hydroxylase needed
30
Glutamine function
TRANSPORTS NH3 from peripheral tissues to kidney
Alanine is also important in transport
31
What happens to glutamine when there is excess NH4+?
Decrease alpha-ketoglutarate --> TCA cycle inhibited
32
Orotic acid
OVERPRODUCED by carbamoyl phosphate synthetase II (CPS II) when there's block in urea cycle
HIGH orotic acid found in ornithine transcarbamylase (OTC) deficiency, citrullinemia
33
Deficiencies of Vit B6, B12, folate
elevated homocysteine --> atherosclerosis, thrombotic events
34
Formation of GABA (y-aminobutyrate)
Decarboxylation of glutamate
35
Arginase
Produces urea + ornithine from arginine
deficiency in arginase (can't get rid of protein products via urea) --> need to have low-protein diet
ornithine transport into mitochondria essential for urea formation; lack of transport --> accumulation of AMMONIA --> DAMAGE to brain (need to restrict protein intake)
36
Kinesin
Microtubule-associated, ATP-powered motor protein
| Anterograde transport of neurotransmitter-containing secretory vesicles down synaptic terminals
37
B12 deficiency
1. Dorsal columns - position and vibration sensation
2. Lateral corticospinal tracts - UMN - spastic paresis, hyperreflexia, Babinski sign
3. Axonal degeneration of peripheral nerves
"Subacute combined degeneration" - degeneration of both ascending (dorsal columns) and descending (corticospinal tract) pathways
Similiar to tabes dorsalis (neurosyphilis) except tabes dorsalis does NOT involve corticospinal tract (no UMN deficits)
38
Peroxisomes; function? Diseases associated?
Beta oxidation of very long chain FA
Alpha oxidation of branched chain FA (phytanic acid)
```
Refsum disease (accumulation of phytanic acid)
Zellweger syndrome (cannot form proper myelin in CNS)
```
39
Proteasomes
Degrade unneeded or improprerly formed intracellular proteins to small polypeptides/aa
Degrade viral proteins for expression on MHC Class I for recognition by T lymphocytes
40
Lysosomes
Degrades FA, carbohydrates, proteins, nucleic acids
41
Vitamin B12 deficiency
Increased homocysteine + methylmalonic acid levels
Folate deficiency - only homocysteine elevated
42
Heme oxygenase
Converts heme to biliverdin (green color of bruise)
43
Ferrochelatase
Heme synthesis (final step)
44
Uroporphyrinogen decarboxylase
defective in porphyria cutanea tarda (PCT) - most common porphyria
needed for production of heme
45
Bilirubin glucuronyl transferase
Conjugation of bilirubin to glucuronic acid
46
Methemoglobin reductase
reduction of methemoglobin (Fe3+) to hemoglobin (via oxidation of NADH)
47
Function of smooth ER
Steroid and phospholipid biosynthesis
(ACTH -- stimulates adrenal cortex to make glucocorticoids; also induces adrenals to produce mineralcorticoids and androgens to a lesser extent)
Detoxification
Specilalized SER = sarcoplasmic reticulum in striated muscle cells
48
Function of rough ER
Makes secretory, lysosomal, and integral membrane proteins
COP II coated transport vesicles transfer proteins from RER to Golgi
49
How does PTH increase 1,25-dihydroxyvitamin D conversion? (hint: enzyme)
Increase renal enzyme 1-alpha hydroxylase
PTH also increase osteoblastic bone resorption, increase Ca2+ reabsorption in distal renal tubule
50
Substance P
Pain neurotransmitter in PNS and CNS
CNS: substance P - regulate mood, anxiety, stress behavior
PNS: Capsaicin (in peppers) decrease level of substance P --> reduces pain
51
C3 deficiency
Recurrent infection w/ encapsulated organisms (no complement)
52
C5-9 deficiency
Membrane attack complex (MAC) can't form --> N. meningitidis & N. gonorrhea infections
53
Chronic granulomatous disease (CGD); increases susceptibility to which types of organisms?
Intracellular killing defect
ESP. susceptible to catalase+ S. aureus (phagocytosed but not killed)
Recurrent suppurative infections (abscesses)
54
Northern vs Southern vs Western blots
Northern - mRNA
Southern - DNA
Western - proteins
ELISA -- measures amount of protein (quantitative)
55
Southwestern blot
DNA-binding protein identified (using dsDNA)
c-Jun and c-Fos are nuclear transcription factors --> bind DNA via leucine zipper motif
c-Jun and c-Fos are proto-oncogenes
56
Vitamin deficiency that mimics Friedreich ataxia
Vitamin E deficiency
occurs in pts. w/ fat malabsorption, abetalipoproteinemia, low birth weight infants
degeneration of spinocerebellar tracts, dorsal column of spinal cord, & peripheral nerves
symptoms:
ataxia, dysarthria, loss of position & vibration sensation
57
Thiamine deficiency
Vitamin B1 - alcoholics & malnourished patients
ataxia, confusion, ophthalmoplegia
58
Creutzfeldt-Jacob disease
Rapidly progressive dementia & myoclonic jerks of extremities
59
Most important regulators of coronary blood flow
NO and adenosine (product of ATP metabolism)
60
How is NO produced?
Synthesized from arginine + O2 via endothelial nitric oxide synthase (eNOS)
61
Role of NO; what other molecule has vasodilatory actions like NO in small coronary arterioles?
NO released via signals from Ach and NE, platelet products, thrombin, histamine, bradykinin, and endothelin
Regulates flow-mediated vasodilation in large arteries and pre-arteriolar vessels
Acts within vascular smooth muscle cells --> increase production of guanylate cyclase-mediated cGMP and cause smooth muscle relaxation
Adenosine = vasodilation in small coronary arterioles
62
CFTR gene
Codon deletion of phenylalanine at position 508 on CFTR protein
63
Paneth cells
located at base of intestinal crypts
phagocytic & secretory properties (1st line immune defense)
```
secrete lysozyme (capable of dissolving cell wall)
secrete defensins (antimicrobial and antiparasitic properties)
```
64
What gene allows cancer cells to become resistant to various anticancer agents? What product does gene make? Action of product?
Multidrug resistance gene (MDR1) --> P-glycoprotein
P-glycoprotein is a ATP-dependent efflux pump --> reduce influx of drugs and increase efflux of drugs from cytosol
P-glycoprotein usually functions as protective barrier at kidneys, intestines, and CNS (does not allow foreign substances to enter)
65
Where is P-glycoprotein normally expressed?
P-glycoprotein protects intestinal, renal tubular epithelium, and CNS from penetration by foreign compounds
66
Tyrosine kinase receptors (function)
Mediate effects of hormones that promote anabolism & cell growth
Insulin
Insulin-like growth factor 1
Epidermal growth factor
Platelet-derived growth factor
67
alpha2-adrenergic vs. beta2-adrenergic effect on insulin
alpha2-adrenergic decrease insulin release
| beta2-adrenergic increase insulin release
68
Riboflavin (vitamin B2) - important biochemical pathway?
TCA
Riboflavin - precursor of FMN and FAD
FAD in TCA cycle serves as coenzyme for succinate dehydrogenase (succinate --> fumarate)
69
Succinate dehydrogenase action
Succinate --> fumarate
| occurs in inner mitochondrial membrane (part of electron transport chain)
70
G6PD
rate limiting enzyme for pentose phosphate pathway
supplies NADPH for glutathione reduction in RBCs
71
What does NADPH reduce (heme importance)
NADPH reduces glutathione in RBCs
72
HMG-CoA reductase is rate-limiting enzyme in what pathway?
Cholesterol synthesis
73
Charcot-Bouchard pseudoaneurysms
```
HTN
Small arteries -- basal ganglia & internal capsule
Intracerebral hemorrhage (basal ganglia, internal capsule, thalamus, pons)
Sudden onset of focal deficits
```
74
Berry (saccular) aneurysms
AKPKD, Marfan, Ehlers-Danlos syndrome
Circle of Willis, anterior & posterior communicating, middle cerebral a.
Subarachnoid hemorrhage
Sudden onset headache; altered level of consciousness
75
HTN leads to what kind of hemorrhage in brain? Why?
Intraparenchymal hemorrhage -- hyaline arteriolosclerosis (tiny arterioles) esp. in basal ganglia
76
Hypoxic encephalopathy - part of brain affected?
decreased oxygenation of blood -- GLOBAL ischemia
77
Most common cause of cerebral ischemia (ischemic stroke)
Carotid artery atherosclerosis
Cardiac embolism
Resembles hemorrhagic stroke (clinical symptoms)
CT scans do not show hemorrhage
78
HbS substitution
Valine (nonpolar) replaces glutamic acid (negative)
79
HbC substitution
Lysine (+) replaces glutamic acid
| Mild chronic hemolytic anemia
Contrast w/ HbS -- allows hydrophbic interaction among Hgb molecules
80
Migration on gel electrophoresis from cathode (-) to anode (+) between HbA, HbS, HbC
HbA travels quickest
| HbC travels slowest (bc it has lysine + charge)
81
Tight junctions (zonula occludens)
mediator of blood-brain barrier between endothelial cells of CNS capillaries; solutes and fluids can't move freely across capillary membrane
"zonula occludens occludes entry of substances into cells --> effective barrier!"
82
Hemidesmosomes
bind the basal layer of epithelial cells to basement membrane
diseases of hemidesmosome = bullous pemphigoid
83
Desmosomes
"spot welds" anchors hold adjoining cells together
seen in stratum spinosum of skin
84
Gap junctions
allows free exchange of solute and fluid between adjacent cells; typically formed by connexin proteins
"connexin connects adjacent cells"
85
Lactic acidosis (molecules involved)
glycolysis generates pyruvate
pyruvate converted to lactate INSTEAD of acetyl-coA
86
3 molecular causes of Down syndrome
a) Trisomy 21 - meiotic nondisjunction (failure of homologous chromosomes to separate during meiosis)
b) Unbalanced Robertsonian translocations - extra arm of chromosome 21 attached to another chromosome (translocation)
c) Mosaicism - pt. has 2 cell lines (one normal genotype and one w/ trisomy 21)
87
Genetic syndromes w/ deletions
Cri du chat (5p deletion)
Prader-Willi (15q)
Angelman (15q)
88
Dopamine hydroxylase
Conversion of dopamine to NE
89
Phenylalanine hydroxylase; relate to adrenergics; relate to TCA cycle?
Conversion of phenylalanine to tyrosine
No tyrosine --> no conversion to DOPA (melanin + catecholamines)
No tyrosine --> no conversion to homogentisate (fumarate --> TCA cycle)
90
What type of ion channels do nicotinic receptors work on?
Ligand-gated ion channels
Influx of Ca2+ --> fusion of storage vesicles --> Ach release
Na+ and Ca2+ influx
K+ outflux
91
Binding of EPI to a-1 adrenoceptors
Activation of IP3 pathway (inositol pathway) --> Increase intracellular Ca2+ --> smooth muscle contraction
92
B1 and B2 adrenoceptors associated w/ what signaling pathway?
cAMP signal transudction --> protein kinase A activation
93
M1 and M3 muscarinic receptors utilize what signaling pathway?
IP3 --> increase intracellular Ca2+ --> protein kinase C
94
M2 muscarinic receptors utilize what signaling pathway?
inhibits adenylyl cyclase --> cAMP --> decrease intracellular Ca2+
95
What is special about 16S rRNA in prokaryotic ribosomes?
16S rRNA strand is only piece of rRNA found in 30S subunit -- > expresses complimentary sequence to Shine-Dalgarno sequence (upstream from AUG codon) --> initiator tRNA binds AUG codon --> protein synthesis begins
96
Function of peptidyltransferase
on 23S rRNA of 50S subunit -- peptide bond formation in protein translation
97
Elongation factor G found in prokaryotes; function?
Translocation; step requires GTP
98
Hypoglycemia after prolonged fasting w/ inappropriately low levels of ketone bodies --> what is impaired?
acyl-CoA dehydrogenase
impaired B-oxidation --> no gluconeogenesis --> severe hypoglycemia
99
Enzyme that catalyzes first step in FA synthesis
Acetyl coA carboxylase
enzyme is suppressed during prolonged fasting/starvation
100
Glycogen phosphorylase
Glycogenolysis - maintain plasma glucose levels during early fasting (until liver glycogen stores are depleted)
removes single glucose residues from a-1,4-linkages within glycogen molecules
depletion in muscle phosphorylase --> muscle cramping & fatigue w/ exercise (McArdle syndrome)
101
a-1,4-glucosidase (acid maltase) deficiency
Pompe disease --> glycogen accumulation in lysosomes
Cardiomegaly
Hypotonia
Hypoglycemia
Early demise
102
Metabolism of what causes increased levels of propionic acid (4aa + 2 others); what is propionic acid converted to? Significance?
```
Branched chain aa:
Isoleucine
Valine
Threonine
Methionine
+
Cholesterol
Odd-chain fatty acids
```
Propionic acid converted to methylmalonic acid by biotin-depedent carboxylation
Isomerization of methylmalonyl coA --> succinyl coA --> TCA cycle
103
Deficiency of propionyl coA carboxylase
Propionic acidemia due to propionyl coA accumulation
Propionic acid is intermediate in catabolism of branched chain aa (valine, isoleucine, threonine, methionine)
104
Effects of carinitine deficiency
Impaired fatty acid transport into mitochondria --> LACK of ketone body production
105
Function of lac operon in E. coli
In presence of lactose --> lactose binds repressor protein --> repressor protein can't bind the operator (to repress operator) --> no repression leads to INCREASED transcription of lac operon structural genes --> increased utilization of lactose
106
How does glucose inhibit lac operon?
Glucose decreases adenylate cyclase --> low intracellular cAMP --> poor binding of catabolite activator protein (CAP) to CAP-DNA binding domain --> decreased expression of structural genes of lac operon
107
Breakdown of maltose
Glucose + Glucose
108
Aldolases (A, B, C) responsible for breakdown of what? What products are generated
Fructose-1,6-bisphosphate & Fructose-1-phosphate are broken down by aldolases
Products yielded are Glyceraldehyde-3-P and DHAP (dihydroacetone phosphate)
109
What undergoes decarboxylation to form GABA?
Glutamate
110
How is acetycholine synthesized? Via what enzyme?
Choline + acetyl-CoA via choline acetyltransferase
111
Role of glycine in CNS
Inhibitory post-synaptic hyperpolarizing potential
Binds to glycine receptors --> Cl- enters neuron via inotropic receptors
112
What does PCR require?
1) DNA template (region of DNA to be amplified)
2) Two primers (flanking sequences of target DNA)
3) DNA polymerase (replicates target DNA)
4) Deoxynucleotide triphosphates (require to build new DNA strands)
113
5' --> 3' exonuclease activity
vs.
3' --> 5' exonuclease activity
5' --> 3' exonuclease activity: removes RNA primers & damaged DNA
3' --> 5' exonuclease activity: proofreading - removes mismatched nucleotides
114
Pompe's disease
Normal blood sugar
Normal glycogen structure
Severe cardiomegaly
Glycogen accumulation in lysosomes
115
McArdle's disease
Muscle glycogen phosphorylase deficiency (can't break down glycogen to glucose-1-phosphate)
Weakness/fatigue w/ exercise
Little or no rise in blood lactate levels after exercise
High level of glycogen in muscles
116
Pyruvate kinase deficiency
PEP (phosphoenolpyruvate) can't be converted to pyruvate
Chronic hemolytic anemia
Splenomegaly
Poor exercise intolerance (won't see increased lactic acid during exercise bc no pyruvate is made)
117
Transcription enhancers: location?
Enhancers increase rate of transcription initiation via protein binding & interactions w/ transcription factors bound to promoter sequences
Enhancers located upstream or downstream; near gene or thousands of base pairs away
118
Promoter: location?
Binding sites for transcription factors and RNA polyermase II (eukaryotic transcription)
TATA (Hogness box) -- 25 nucleotides upstream from gene being transcribed
CAAT box -- 70 to 80 bases upstream from gene
119
How is cDNA produced?
mRNA is template and used by reverse transcriptase (RT) to make cDNA
120
IGF-1
produced in liver and elsewhere in response to GH
binds cell-membrane associated receptors w/ tyorsine kinase activity --> anti-apoptosis & anabolic effects
121
What type of receptor is insulin?
Transmembrane tyrosine kinase - binds insulin
122
k-RAS
G-protein involved in cell signaling
common in pancreatic malignancies
123
N-myc
transcription factor -- able to bind DNA (can be detected by DNA probes)
124
Pantothenic acid; function? What symptoms do patients complain of?
Pantothenic acid = coenzyme A
Essential for acetylation rxns - including TCA cycle
OAA --> citrate requires coenzyme A
Needed in synthesis of vitamin A & D, cholesterol, steroids, heme A, fatty acids, amino acids, proteins
seen in malnourished people w/ paresthesias, dysesthesthesias "burning feet syndrome" & GI distress
125
DNA polymerase I
removes RNA primers, replaces spaces w/ DNA
lagging strand needs more action of DNA primase (lay down primers) and DNA ligase (joins fragments)
126
Leptin
Protein hormone
Produced by adiopocytes (proportional to amount of stored fat in body)
Leptin acts on arcuate nucleus of hypothalmus:
Decrease neuropeptide Y
Increase alpha-MSH
127
Neuropeptide Y
Appetite stimulant
decreased by leptin
128
alpha-melanocyte stimulating hormone (alpha-MSH)
produced by cleavage of proopiomelanocortin (POMC)
inhibits food intake
increased by leptin
129
Primase
DNA-dependent RNA polymerase
Incorporates short RNA primers into replicating DNA
130
Deficiencies in strengthening collagen leads to Ehlers-Danlos; what enzymes missing?
Lysyl-hydroxylase/prolyl hydroxylase: hydroxylation of proline & lysine residues (posttranslational modification in ER)
Pro-collagen peptidase: N & C terminal propeptide cleavage --> collagen fibril (insoluble collagen molecules) -- outside of cell
Lysyl oxidase: covalently crosslinks collagen fibrils
131
Anti-phospholipid antibodies; found in what condition? Symptoms?
SLE
causes hypercoagulability & paradoxical PTT prolongation (appears to have clotting problem even though pt. is really hypercoagulable)
132
Antibodies to citrullinated peptides/proteins; associated w/ what condition? What aa is involved? Where does citrulline come from?
Rheumatoid arthritis
tissue inflammation --> arginine residues --> vimentin converted to citrulline --> protein shape altered (becomes like an antigen) --> immune reaction
RA can be confirmed w/ anti-cyclic citrullinated peptide antibodies
133
Splice site mutations
Production of larger proteins w/ altered function
However, still retain immunoreactivity of normal protein
134
Relationship btwn high NADH and gluconeogenesis
High NADH --> inhibits gluconeogenesis
Alcoholics --> NAD+ reduced to NADH
High NADH --> no gluconeogenesis
HYPOGLYCEMIA induced by alcohol
135
Lack of ApoE3 and ApoE4
Liver can't remove chlyomicrons and VLDL remnants from circulation --> elevations in cholesterol & TGs
136
Lack of ApoC-II; what enzyme does ApoC-II activate?
On chylomicrons and VLDL
Hyperchlyomicronemia
Lipoprotein lipase is activated by apoC-II
137
ApoA-I
LCAT activation (cholesterol esterification)
Impaired formation of mature HDL
138
ApoB-48
Chylomicron assembly & secretion by intestine
139
ApoB-100
LDL particle uptake by extrahepatic tissue
140
Vagal stimulation of bronchial smooth muscle --> ?
Constriction of smooth muscle via Ach from postganglionic paraysmpathetic neurons on M3 receptors
Increase mucus secretions + bronchoconstriction --> increase airflow resistance --> increase WORK of breathing
141
What happens to expiratory flow rates with increased airway resistance?
Expiratory flow rates decrease
Ohm's law:
Flow = pressure/resistance
142
Definition of partial pressure of O2 in blood:
Amount of oxygen dissolved in plasma
143
What types of drugs causes Fe2+ --> Fe3+ (methemoglobin); what is significant about Fe3+?
Nitrites oxidize Fe2+ to ferric Fe3+
Fe3+ causes dusky discoloration to skin (like cyanosis) since it can't carry O2 --> anemic state induced
Fe3+ tightly binds cyanide
144
CO poisoning:
| O2 content, PO2, % saturation
```
PO2 normal
% saturation = decrease (CO completes w/ O2)
O2 content (dissolved and O2 attached to Hb) = decrease
```
145
Anemia:
| O2 content, PO2, % saturation
PO2 normal
% saturation normal
O2 content = decrease
146
Polycythemia:
| O2 content, PO2, % saturation
PO2 normal
% saturation normal
O2 content = increase
147
Steps in bilirubin metabolism (4)
Uptake from bloodstream
Storage in hepatocytes
Conjugation w/ glucuronic acid
Biliary excretion
148
Conservative mutation
Missense mutation where one aa is replaced w/ another aa that has similar biochemical characteristics
149
Autosomal recessive inheritance pattern
Enzyme deficiencies (e.g. classical galactosemia)
150
Classic galactosemia
galactose-1-phosphate uridyl transferase deficiency
vomiting, lethargy, failure to thrive soon after breastfeeding begins
improves when placed on galactose free formula
151
Phosphatidylcholine significance?
Also called lecithin -- component of surfactant
Lecithin/sphingomyelin ratio needs to be >2.0 to avoid neonatal hylaine membrane disease (when there's not adequate surfactant production)
152
Gene deletion in renal cell carcinomas
VHL gene on chromosome 3p
hereditary renal cell carcinoma associated w/ Von Hippel-Lindau disease
153
Calculation of A-a gradient
Pressure of O2 in alveoli - Pressure of O2 in systemic blood arteries
154
Normal A-a gradient is what? What if there is an excess A-a gradient value?
A-a gradient is normallly 10-15mmHg
Gradient exceeding >15mmHg indicates V/Q mismatch (ventilation/perfusion) OR diffusion impairment (eg. hyaline membrane diseases)
155
If person has normal A-a gradient but low PaO2, what does this mean?
The low PaO2 is directly related to low PAO2 (limited amount of O2 from alveoli to be exchanged)
156
Hypoxemia when there is normal A-a gradient; causes?
Alveolar hypoventilation OR inspiration of air with low pO2 (eg high altitude)
Hypoventilation causes:
- - suppressed central respiratory drive (sedative overdose, sleep apnea)
- - decreased inspiratory capacity (myasthenia gravis, obesity)
157
Right to left shunt and its effect on A-a gradient
Venous blood bypasses lungs --> enters arterial circulation --> decrease PaO2
A-a gradient increased (since there's a lot of O2 for exchange in alveoli, but there's venous mixing in arteries that should be O2 rich going out to rest of body from lungs)
158
4 causes of hypoxemia; one cause has normal A-a gradient; which one?
1) alveolar hypoventilation (normal A-a gradient)
2) V/Q mismatch
3) diffusion impairment
4) R --> L shunting
159
V/Q mismatch
```
Common cause of hypoxemia
Poor ventilation (can't inspire enough O2 into alveoli) of well-perfused alveoli --> physiologic shunting --> increased A-a gradient
```
V/Q mismatch in pneumonia, obstructive pulmonary disease, pulmonary embolism (obstruction of air flow --> less O2 available --> less ventilation)
160
Normal values for PaCO2 and PaO2 (partial pressures of gases in pulmonary vein -- going back from the lungs)
```
PaO2 = 104mmHg
PaCO2 = 40mmHg
```
161
What enzyme is missing in xeroderma pigmentosum?
UV endonuclease
can't excise thymine dimers caused by UV light; usually thymine dimers excised and DNA replaced by polymerase & ligase
162
What rxns need lipoic acid as a coenzyme?
Pyruvate --> Acetyl CoA via pyruvate dehydrogenase
a-ketoglutarate --> succinyl-CoA via a-ketoglutarate dehydrogenase complex
163
Histone acetylation vs DNA methylation
Histone acetylation --> euchromatin --> transcriptionally active
DNA methylation --> heterochromatin --> low transcriptional activity
164
Person is at high altitude in the mountains; what physiology is occuring?
Hypoxemia --> carotid & aortic body chemoreceptors --> increased ventilatory drive --> hyperventilation --> respiratory alkalosis --> increase in blood pH, decrease in PaCO2
165
Increased intraplaque enzyme activity predisposes person to MI; what is enzyme?
Metalloproteinases - due to activated macrophages --> DEGRADES collagen --> destabilized plaques + ongoing intimal inflammation --> MI
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prolyl 4-hydroxylase
hydroxylation of proline on procollagen --> stable collagen triple helix
167
lysyl oxidase
conversion of lysine residues --> aldehyde in collagen fibers
high lysyl oxidase --> atheroma stabilization (strengthening collagen in fibrous cap)
168
Enzyme deficient in Ehlers-Danlos syndrome
Procollagen peptidase
disorganized collagen bundles --> stretchable skin, hypermobile joints
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Alternative splicing (post-transcriptional processing) leads to variation of mRNA sequences --> different proteins; what diseases can be caused by alternative splicing?
Beta-thalassemia
Cancer
Retroviruses (like HIV)
170
DNA gene rearrangement - where does this occur?
Development and maturation of B cells and T cells
VDJ gene recombination takes place in primary lymphoid tissue
171
What is involved in rxn of UDP-galactose --> galactosyl B-1,4-glucose?
Lactose synthase
| galactosyl B-1,4-glucose = lactose!
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Purpose of HMP shunt
makes REDUCING agent NADPH to prevent oxidative damage to RBCs
NADPH used w/ glutathione reductase to keep glutathione in REDUCED state
H2O2 is detoxified via glutathione peroxidase
rate limiting enzyme of HMP shunt (glucose 6-phosphate dehydrogenase aka G6PD)
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Pyruvate kinase deficiency - effect on RBCs
Defective RBC glycolysis --> decreased availability of ATP --> RBC membrane becomes stiff/deformed --> chronic hemolytic anemia
174
G6PD deficiency vs. Glutathione reductase deficiency
Similar symptoms and pathophysiology
G6PD -- defect in HMP shunt --> glutathione reduction impaired --> failure to produce NADPH
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2 growth factors that promote angiogenesis; what can also indirectly promote angiogenesis?
VEGF (vascular endothelial growth factor)
FGF (fibroblast growth factor)
Proinflammatory cytokines (IL-1 and INF-y) indirectly promotes angiogenesis via VEGF expression
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Somatomedin C
Same as insulin-like growth factor (IGF-1)
Synthesized by hepatocytes --> stimulate cell growth and multiplication
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Pyruvate carboxylase function; what cofactor is needed?
First step of gluconeogenesis
Converts pyruvate to oxaloacetate (OAA)
Requires biotin as cofactor (in mitochondria)
178
Ornithine transcarbamoylase; deficiency leads to what clinical disease?
Secondary step of urea cycle:
Ornithine & carbamoyl phosphate combine --> forms CITRULLINE
Occurs in mitochondria
Deficiency leads to hyperammonemia & mental retardation
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3-hydroxy-3-methylglutaryl-coA (HMG CoA) lyase: action
Ketogenesis from HMG CoA
180
How is HMG CoA formed?
Degradation of leucine (strictly ketogenic aa) --> HMG CoA
HMG CoA synthase also makes HMG CoA
HMG CoA intermediate in forming cholesterol
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What metabolic processes occur in mitochondria? What process does not?
B-oxidation of FA
Ketogenesis
Citric acid cycle
Urea cycle:
CPS1 (carbamoyl phosphate synthetase 1) & ornithine transcarbamoylase
Pyruvate carboxylation
-------
Pentose phosphate pathway occurs in CYTOPLASM (transketolase is enzyme involved)
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PTH effect on osteoclasts
PTH acts directly on osteoblasts; INDIRECTLY on osteoclasts
PTH increase production of:
RANK-ligand and monocyte colony-stimulating factor (M-CSF) --> maturation of osteoclasts
PTH decrease osteoprotegerin (OPG); lower OPG allows more RANK-ligand interaction w/ osteoclasts --> more bone resorption
183
PTH effect on Ca2+ and phosphorous (in bone vs. in kidneys)
PTH causes efflux of Ca2+ and phosphorous from bone -- therefore BOTH Ca2+ and phosphorous levels will increase;
HOWEVER.. PTH INCREASE Ca2+ absorption and DECREASE phosphorous reabsorption from kidneys
184
TGF-B: effects?
Transforming growth factor beta
Tissue regeneration & repair
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y-interferon: What cells secrete this factor? What are the effects?
secreted by helper T cells
activate macrophages --> promote adaptive immunity against intracellular pathogens
186
What vitamin is required for carboxylation of glutamates?
Vitamin K
Converts glutamyl residues to y-carboxyglutamates --> clotting factors VII, IX, X
protein C and S (anticoagulants) also need carboxylation of glutatmates for activation
187
Sources of Vitamin K
Beef liver
Green tea
Dark green vegetables
188
Vitamin A deficiency
night blindness
xerophthalmia (can't produce tears)
vulnerable to infection (measles)
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Vitamin B1 deficiency
Thiamine deficiency
Beriberi and Wernicke syndrome
190
Vitamin B2 deficiency
Riboflavin deficiency
Stomatitis (inflammation of mucus lining of all structures of mouth)
Corneal vascularization
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Differentiate btwn B2 and B6 deficiency
B2 (riboflavin) & B6 (pyridoxine) both have:
a) Cheilosis (fissuring/drying of surface ofl ips, angles of mouth)
b) Glossitis
c) Dermatitis
B6: peripheral neuropathy
B2: Stomatitis, corneal vascularization
192
Deficiency of HGPRT in Lesch-Nyhan; increase in what molecule occurs consequently?
PRPP synthetase is increased (necessary for de novo purine synthesis since purines guanine and hypoxanthine not recycled)
Guanine and hypoxanthine bases not recycled and excreted in urine = hyperuricemia
