Exam 1 Flashcards
(246 cards)
1
Q
Name the aliphatic or hydrocarbon or non- polar amino acids.
A
Gly, Ala, Val, Leu, Ile
2
Q
Name the sulfur containing amino acids
A
Cys, Met
3
Q
Name the aromatic amino acids.
A
Phe, Tyr, Trp
4
Q
Name the imino amino acids.
A
Pro
5
Q
Name the Neutral amino acids.
A
Ser, Thr, Asn, Gln
6
Q
Name the acidic amino acids. What charge at neutral pH?
A
Asp, Glu, -
7
Q
Name the basic amino acids. What charge at neutral pH?
A
His, Lys, Arg, +
8
Q
What is the three letter abbreviation for Glycine?
A
Gly
9
Q
What is the three letter abbreviation for Alanine?
A
Ala
10
Q
What is the three letter abbreviation for Valine?
A
Val
11
Q
What is the three letter abbreviation for Leucine?
A
Leu
12
Q
What is the three letter abbreviation for Isoleucine?
A
Ile
13
Q
What is the three letter abbreviation for Cysteine?
A
Cys
14
Q
What is the three letter abbreviation for Methionine?
A
Met
15
Q
What is the three letter abbreviation for Phenylalanine?
A
Phe
16
Q
What is the three letter abbreviation for Tyrosine?
A
Tyr
17
Q
What is the three letter abbreviation for Tryptophan?
A
Trp
18
Q
What is the three letter abbreviation for Proline?
A
Pro
19
Q
What is the three letter abbreviation for Serine?
A
Ser
20
Q
What is the three letter abbreviation for Threonine?
A
Thr
21
Q
What is the three letter abbreviation for Asparagine?
A
Asn
22
Q
What is the three letter abbreviation for Glutamine?
A
Gln
23
Q
What is the three letter abbreviation for Aspartic acid?
A
Asp
24
Q
What is the three letter abbreviation for Glutamic acid?
A
Glu
25
What is the three letter abbreviation for Histidine?
His
26
What is the three letter abbreviation for Lysine?
Lys
27
What is the three letter abbreviation for Arginine?
Arg
28
What is the side chain for Gly?
H
29
What is the side chain for Ala?
CH3
30
What is the side chain for Cys?
CH2-SH
31
What is the side chain for Ser?
CH2-OH
32
What are the classifications for amino acids?
Alaphatic, Sulfur, Imino, Neutral, Acidic, Basic or Amide or Cyclic Amino
33
Keq=
[products]/[reactants]
34
^G=
^H - T^S
35
if Keq > 1, then...
rxn favors products
36
if Keq<1, then...
rxn favors reactants
37
if Keq = 1
equilibrium
38
pH =
log 1/[H+] or -Log [H+]
39
pH=pKa when?
pI
40
pK +log[base]/[acid] =
pH
41
Buffering zone =
pKa +/- 1 pH unit
42
Carbonic Acid
H2CO3
43
Bicarbonate
HCO3-
44
CO2 + H2O =
H+ + HCO3-
45
What is the intermediate of this rxn? CO2 + H2O = HCO3- + H+
H2CO3
46
if pH > pKa, then
unprotonated
47
if pH < pKa, then
protonated
48
pHs charge is?
positive
49
pH>pI then the protein's charge is?
negative
50
Which amino acids are strongly polar?
Arg, Lys, Asp, Glu
51
Which amino acids are very hydrophobic?
Leu, Ile, Phe, Met, Val, Ala
52
Which amino acids are diprotic?
Ala, Asn, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Val
53
Which amino acids are polyprotic?
Glu, Arg, Lys, Asp, Cys, His, Tyr
54
N=
equivalents/L
55
equivalents=
wt(g)/EW
56
EW+
MW/n n=# of H or OH per molecule
57
weight/volume%
g/100mL or g/dL
58
milligram %
mg/100mL or mg/dL
59
log (10^x) =
x
60
10^-x =
1/10^x
61
log 0.1
-1
62
log 0.001
-2
63
log 1
0
64
log 10
1
65
log 100
2
66
if log (x) = y then
x = 10^y
67
Negative regulator of hemoglobin?
pH, CO2, BPG
68
Type 1 collagen is functionally set up how? Where is it found?
Fibrillar, Bone, skin, tendon, scar tissue, heart valve, intestinal and uterine wall
69
Type IV collagen is functionally set up how? Where is it found?
Network, Basement membrane, lens capsule
70
Collagen requires post-translational modification of amino acids by what enzyme and what cofactor? What disease is associated with the lack of the cofactor?
prolyl hydroxylase, vitamin C, scurvy
71
Characterstics of collagen.
rigid and strong, glycosylated, sequence repeats every third is Gly, triple helix, individual is left handed helix cord of three is right handed helix
72
Ehlers-Danlos Syndrome (EDS)
disease of collagen struct./strength, hyperextensible skin, poor wound healing, ragged scarring, and joint hypermobility (thumb sign)
73
Osteogenesis Imperfecta
type I collagen disorder, mutation in COL1A1 and COL1A2 gene, "Brittle bone disease", multiple fractures w/ no apperent trauma, skeletal disformities, blue sclerae, autosomal dominant
74
Matrix proteins are made by what cells?
fibroblasts, osteoblasts, chondroblasts
75
matrix is mostly what molecules?
proteoglycans and fibrous proteins
76
Ground substance is made up of what?
glycosaminoglycans (GAGs)
77
Name 5 types of GAGs and where they are foudn
Chondroitin sulfate in cartilage, tendons, and ligaments; dermatan sulfate in skin, blood vessels, and heart; heparin and heapran sulfate in cell surface of blood vessel walls; keratin sulfate in same as CS; and hyaluronan in synovial fluid and vitreous humor of the eye.
78
What is the repeating sequence that makes up hyaluronan? whys is it unique from other GAGs?
glucuronic acid and N-acetylglucosamine, unique because it is not synthesized on a core protein
79
Name the functions of proteoglycans.
Primarily rigidity in hydrated spaces, bind growth factors ( insulin like, transforming) to serve as a reservoir, bind proteolytic enzymes and inhibitors, degradation is important in regulation of cell migration and tissue remodeling and cancer
80
What is mucopolysaccharidoses?
lysosomal storage disorder due to defective GAG degradation, normal at birth, develop dismorphic features, coarse facial hair hirsutism, macrocephaly, learning disabilities
81
Hurler Syndrome
MPS type I, deficiency of alpha-iduronidase, dermatan sulfate and heparin sulfate, gargoylism, fatal cardiomyopathy
82
Hunter syndrome
MPS type II, x-linked, deficiency of iduronate sulfatase which helps degrade heparin sulfate and dermatan sulfate
83
Fibronectin
ECM, major glycoprotein, bound to integrins on surface of matrix cells
84
Marfan Syndrome
disorder of fibrillin defects, tall stature, skeletal deformities, long thin bones, joint hypermobility, positive wrist and thumb sign, mitral valve prolapse, loss of elasticity in aortic root may lead to aneurysm and potentially aortic dissection
85
Basal Lamina is what? What are its two layers?
mat of extracellular matrix, lamina lucida (mostly laminin) and lamina densa (mostly collagen)
86
Purines
A, G, two rings
87
Pyrimadines
C, T, one ring
88
Three factors stabilizing DNA
H bonds, Base stacking, ions
89
Helicase
enzyme separating DNA during replication
90
topoisomerase
I and II, relax supercoiling, 1- breaks sugar phosphate backbone of one strand then swivels and relegates broken strand, 2 breaks both strands of one loop then passes the other strand through the break and relegates.
91
RNA primer is made by what?
DNA primase
92
DNA Polymerase
elongates synthesis of DNA after RNA primer
93
Fidelity
intrinsic feat. accuracy, proof reading 3'-5' repair, primase 1 in 10k mistakes= low fidelity
94
Lagging strand repair
RNase H- digests and removes RNA primer, DNAPol fills gap, Ligase joins the ends
95
Differences between leading and lagging strand
discontinuos synthesis (lag), frequent repair (lag), frequent ligation (lag), leading strand extended by telomerase and lagging by DNA primase and DNA Pol, Single strand binding proteins (more important on lag)
96
DNA repair types
Proofreading, Lagging strand repair, Mismatch repair, Nucleotide Excision repair, Base excision repair, strand break repair, transcription coupled repair
97
What is spontaneous depurination? how is it repaired
purine group come off phosphate sugar backbone, repaired via BER
98
What does radiation do to DNA? How is it repaired?
Ionizing- strand breaks- non-homologous end joining
| UV- pyr-pyr dimers- NER
99
How do Xenobiotics effect DNA? Repair?
Adducts (covalently modifies base) - direct or NER
100
How can Metabolic Errors effect DNA? repair?
replication past a single strand break- homologous recombination or less likely non-homologous end joining
101
How are proofreading errors fixed?
mismatch repair, 3'-5' exonuclease
102
How does deamination effect DNA? repair?
spontaneous hydrolysis of NH2 (almost always get an unnatural base except methylated C -> T ok but not a great match), BER
103
What is heritable damage? repair?
wrong base but chem. normal, (missense, nonsense, frameshift, silent) or
damaged bases chem and base change or
Insertions and Deletion; BER
104
What is Xeroderma pigmentosum?
UV damage not repaired efficiently, mutation in NER, pyrimidine dimers, basal cell cancer, squamous cell cancer, melanoma
105
rRNA types? funct.?
28s, 18s, 5.8s, 5s, protein translation machinery, most abundant
106
RNA types?
rRNA, mRNA, tRNA, snRNA, snoRNA, miRNA
107
mRNA fact and function?
longest, directs synthesis of proteins
108
tRNA fact and function?
shortest major, carry amino acid residues
109
snRNA fact and function?
uridine rich, mRNA splicing
110
snoRNA fact and function?
small nucleolar, rRNA modification
111
microRNA fact and function?
in cytoplasm, can be in nucleus, mRNA expression
112
lncRNA fact and function?
long non-coding, varied funct. structural, imprinting, etc.
113
Types of RNA Pol? what do they synthesize?
Pol I: rRNA 5.8s, 18s, 28s
Pol II: mRNA, snoRNA, miRNA, snRNA
Pol III: tRNA, 5s rRNA, snRNA
114
Regulation of RNA synth.?
mostly promoter pol complex, alternative splicing, alternative poly A, altenrative initiation points
115
Steps to mRNA synth.
closed complex, open complex, initiation, promoter clearance, elongation, termination, separation of RNA
116
Necessary components of mRNA synth. (pro)
DNA dependent RNA pol, DNA template, cis element on DNA to recruit trans acting factors, nucleotides
117
POL II synth:
Pol II, template, cis seq, trans factors, and nucleotides, GTF, CTD
118
What is the PIC?
preinitiation complex, trans factor, pol II, GTFs, and cis seq.
119
What is the function of CTD?
c-terminus domain,recruits modifying proteins cap mRNa 5'-5' bond (cotranscriptional),
poly A Pol, post-transcriptional, poly
120
2 methods of splicing mRNA
```
invariant A (2'-5' bond, release lariat)
snRNA splicisome U1,2,4,5,6
```
121
rRNA synthesis
Pol I same as Pol II minus CTD ( no capping, splicing, or polyadenylation), synth in cluster (18s, 5.8s, 28s) 45s precursor, in nucleolus genes transcribed, rRNA processed by snoRNA (telomerase) snoRNP (splicisome RNA and protein), and rRNA and ribosomal proteins assembled
122
rRNA modification
chem modified to include pseudouridine or modified 2'Omethyl ribose, each repeated ~100x
123
rRNA cleavage
endonuclease hydrolyzes into 3 fragments, directed by snoRNA (U3)
124
5s RNA synth.
Pol III, separate gene, not processed from precursor
125
tRNA maturation
Pol III, modified bases: pseudouridine, dihydrouridine, and thymidine, 3' terminal CCA = charging
126
miRNA synth/cleavage
Pol II, capped, spliced, polyadenylated, clustered stem loops ( can be from host gene intron), RNase Drosha separate stem loops from sequence, Dicer cuts loop off stem, stem = miRNA
127
Notable structures on tRNA
acceptor stem ( site of CCA tail), D arm, Anticodon arm, anticodon, variable arm, TPsiC arm, methylated bases, irreg. bases inosine and pseudouridine
128
Aminoacyl-tRNA formation
catalyzed by aa tRNA synthetases, 2 step, very important because codon and anticodon rxn independent of AA attached to tRNA
129
3 phases of protein synth.
chain initiation, elongation, termination
130
Chain initiation req.
regulated not ongoing, 1st AA Met, mRNA, GTP, Mg2+, ribosomal subunit, eukaryotic initiation factors, cap binding protein
131
summary of Chain initiation
ribosome dissociation-> 40s and 60s
40s + Tert. complex -> 43s preinitiation comp.
43s PIC + mRNA -> 48s PIC
48s PIC + 60s subunit -> 80s initiation comp.
132
Peptide elongation req.
active 80s initiation comp., aa-tRNA specified by next codon (n+1), 2GTP, Mg2+, Peptidyl transferase, 2 elongation factors (EF-1, EF-2)
133
Peptide elongation summary
For each peptide elongation cycle 2 GTPs hydrolyzed forming a peptide bond, followed by movement by ribosome to next available codon on mRNA
134
Polypeptide termination req.
Active 80s, Termination codon on mRNA, GTP, Peptidyl transferase, release factors (RF-1, RF-3), Mg2+
135
Summary of Polypeptide chain termination
3 termination codons (UAA, UAG, UGA), no known tRNA's w/ comp., codon at A site will cause bindng of RF-1 and RF-3 to catalyze termination
136
Fidelity of Protein Synth. (quality control)
P (processing) bodies, selectively degrade nonsense sequences of mRNA; ubiquitin-proteasome system (UPS) degradation of misfolded protein
137
Regulation of Translation?
miRNA and RNAis bind by base pairing to 3'UTR on specific mRNA prevent translation/trigger destruction, RNP complex known as RISC (RNA-initiated silencing complex) sequester RNA; Riboswitches & gene specific proteins, control specific mRNA by specific metabolites, translation prod, or related protein, ex. IRF ( Iron responsive Factor control of ferritin mRNA)
138
silent mutation
change of a base but codon still codes same amino acid
139
missense mutation
change in base change amino acid coded for, sometimes see phenotypic change ex sickle cell
140
non-sense mutation
base change code for stop instead of a AA
141
deletion/insertion
frame shift mutation, changes entire sequence
142
splice site mutations
consensus sequences if mutated cause in correct splicing ex B-thallasemia
143
trinucleotide repeat expansions
slipping during replication, trinucleotides repeated cause protein aggregates, ex huntingtons
144
How does tetracycline work?
binds to 30s, inhibits binding of aminoacyl-tRNA (pro)
145
How does chloramphenicol work?
inhibits peptidyl transferase of 50s, not used, liver failure, mitochondria
146
How does puromycin work?
premature chain termination, analog of aminoacyl tRNA (pro and eu) not clinically used
147
How does streptomycin work?
binds 30s, inhibition by codon misread
148
How does erythromycin work?
blocks translocation, binds to a protein on 50s, (pro)
149
How does cycloheximide work?
inhibits peptidyl transferase of 60s (eu)
150
How does rifamycin/rifampicin work?
blocks intiation of bacterial RNA synth (transcript.)
151
How does diphtheria toxin (natural) work?
inactivates EF-2, inhibits translocation
152
How does miRNA or RNAi work?
inhibit mRNA translation, cause degradation
153
What role does EF1a and EF2 a play and in what pathway?
protein chain elongation 1a brings a new aatRNA to the a site and takes the tRNA off the e site, 2 helps translocase move the tRNA from a to p site
154
How do mitochondrial protein synthesized in the cytoplasm get into the mitochondria?
have a amphipathic leader sequence, recognized by cytosolic chaperonins, chaperonins direct proteins to outer mitochondrial membrane
155
Secretory proteins/lysosomal proteins synth.
leader sequence recognized once it exits ribosome, elongation halted with binding of SRP, SRP binds to its receptor on ER surface next to ribosome receptor, SRP dissociates, ribosome continues elongation of protein thru receptor into ER lumen
156
Why does glycosylation happen? Types of bonds?
maintain stability, increase solubility, occurs in ER and Golgi, N link oligosaccharide (complex or manose) to Asn, O link oligosaccharide to OH of Ser Thr, now glycoproteins
157
synthesis of o linked glycoproteins
transfer of sugars as nucleoside derivatives to seryl and threonyl residues. enz: glycosyltransferase
158
synthesis of n linked glycoproteins
added en bloc (presynth oligo assembled on dolichopyrophosphate) enz: glycosyltransferase, attach in ER, trim in ER, transport via vesicle to Golgi, trimmed again or monosaccharides added in Golgi, released as secretory protein in secretory granule or phosphorylated attached to manose-6-phosphate receptor and transported w/receptor in vesicle to acidified compartment, separated from receptor, protein cleaved to catalytically activate and transferred to lysosome.
159
Alpha-1-antitrypsin deficiency?
inability to secrete a-1AT into circulationdue to polypeptide mut., emphysema, cirrhosis, hepatocellular carcinoma, unable to degrade, just builds up in cell.
160
I-cell disease (mucolipidosis II)?
defective phosphotransferase activity to mannose, lysosomal enzyme secretion instead of transfer to lysosome, cong. heart fail, pneumonia susceptible
161
Protein phosphorylation
rapidly raise or lower protein activity, depending on target protein and phosphorylation site
162
Proteolytic modification (trimming)
in ER and Golgi, removal of NH2 terminal sequences, stepwise protein maturation
163
Ubiquitylation of protein
degradation by proteasome or signaling (alter function)
164
Acetylation of protein
mech. for enhancement of protein stability, activity, and gene expression
165
hydroxylation of protein
protein cross-linking ex collagen
166
Methylation of protein
regulate protein function and structure
167
Sulfation of protein
amino acid modification and signaling
168
lipid binding to protein
localize proteins in lipid bilayer of membranes
169
Functions of epithelia
selective barrier, protective function, sensory surfaces
170
Epithelial tissue derived from what germ layers. be specific.
Ecto-epidermis, gland of breast, cornea, part of oral and anus
Endo, alimentary canal and glands, most respiratory, distal urogenital
Meso- mesothelium-internal cavities, endothelium- BV and LV lining, epithelia-prox urinary and genital
171
Characteristics of epithelia
cellular( little ECM), Polarized, Numerous CJ, Polygonal, Avascular, Can be removed surgically with underlying CT, Basal surface in contact with Bsal Lamina,
172
What makes up the basal lamina? Describe each.
lamina densa: filametous network of laminins bound by integrins, come collagens type IV, proteoglycans, and glycoproteins
Lamina lucida: CAMs (cell adhesion molecules), fibronectin, laminin receptors
173
What makes up the basement membrane? Describe each layer.
basal lamina: btwn basal surface of epithelium and underlying CT, lamina lucida touching basal side of cells then lamina densa; reticular lamina: reticular fibers (type III collagen), produced by cells in underlying CT
174
what makes up the terminal bar? What makes up that?
multiple junctional complexes, zonula occludens (preserve polarity, separate apical and basal, inhibit protein migration), Zonula adherens, and macula adherens
175
describe simple sqaumous. Where is it found?
single layer, flat cell, endothelium, mesothelium, kidney, lungs
176
describe simple cuboidal. Where is it found?
tall=wide, one layer, nucleus centered, exocrine ducts, ovary, kidney tubule
177
describe simple columnar. Where is it found?
taller than wide, one layer, SI, Colon, Stomach lining, gastric glands, gallbladder
178
describe pseudostratified. Where is it found?
all cell reach BM, nuclei on different levels, trachea, bronchial tree, ductus deferns, efferent ductules and epididymis
179
describe stratified cells?
squamous, cuboidal or columnar, named for cell on the surface
180
Where is stratified squamous?
epidermis, oral cavity, esophagu, vagina
181
Where is stratified cuboidal?
sweat gland ducts, large ducts of exo, anorectal junct.
182
where is stratified columnar?
anorectal junction, largest exo duct
183
Describe transitional epitlium. Where is it?
between cuboidal and squamous, allows distension, squamous when stretched and less layers, more cuboidal when relaxed and more layers, renal calyces, ureters, bladder, urethra
184
What is metaplasia?
change in cell type
185
Name the apical surface specializaions of epithelium.
cilium w/ microtubules, stereo cilium with microfilaments (elongated w/ branched end), microvilli (extension of membrane with actin core) with glycocalyx. microfilaments
186
Name lateral surface specializations of epithelium. describe them.
zonula occludens, zonula adherens (w/actin projection connecting to actin terminal web), macula adherens (w/ tonofilaments connect to actin filaments), lateral interdigitation(inc. plasma membrane surface=more Na/K pumps, rapi H2) transport), gap junction (ions and small molecules), intercellular cannuliculus (liver-bile secretion, specialized membrane around and tight junct.)
187
Name Basal membrane specializations.
basal lamina, reticular lamina, basal unfoldings (present w/ lots of active transport, house mitochondria btwn, kidney tubules
188
what is liable epithelial tissue?
continuously renewed cells by mitotic activity, rates vary ( stomach)
189
what is stable epithelium?
multiply around puberty and in special circumstances, injury, liver, pancreas, thyroid, kidney
190
what is permanent epithelium?
cease multiplication at birth, lens of eye
191
Name the different endocrine gland types.
cord shape or follicle shape, empties into BV nearby no duct
192
Name and describe the exocrine gland types.
Merocrine- secretory vesicle fusses w/ membrane relasing contents
Apocrine- membrane pinches off containing secretory product.
Holocrine- cell dies and product is relased
193
Describe a paracrine gland.
product emptied into ECF to act on target cells locally
194
Where can myoepithelial cells be found?
btwn secretory cell and basement membrane of exocrine glands, assists expression of secretory product into duct
195
Name the reasons for protein synthesis and degradation.
normal protein turnover, gene expression, quality control and peotection (damaged, misfolded, aggregated), cell division, immune response, energy maintainence
196
What are the two proteolytic systems?
UPS, lysosomal system
197
What are lysosomes?
organelle digestion system, membrane enclosed acid hydrolases,
198
list the lysomsomal membrane proteins and their function.
LAMP 1 &2: marker protein; Endolyn: glycoprotein marker, RAB-7: autophagy, CD68: LDL, Cystinosin: transport cysteine, Vacuolar H+ ATPase: allows lysosome to maintain pH 4.7
199
What are the major pathways of lysosomal proteolysis?
Endocytosis, Phoagocytosis, Autophagy (macro, micro, and Chaperone mediated)
200
What is endocytosis for in LP path?
remove and degrade obsolete or damaged serum proteins, brought into cell via receptors or pinocytosis, EE->LE->Lysosome, pH drop whole way in
201
What is phagocytosis for in LP path?
extracellular particles (bacteria or macrophages), purpose is immunity
202
What is autophagy?
destruction of large amounts of intracellular proteins, cellular digestion and quality control
203
What is macroautophagy?
digestion of vaccoules and contents, trafficked to lysosome
204
What is microautophagy?
small particles taken into Lysosome from cytosol vie invagination
205
What is chaperone mediated autophagy?
HSP chaperone recognizes marked protein and attaches, takes it to lysosome (slows with age)
206
How is Macroautophagy affected in post absorptive state
nutrients and insulin upregulate mTOR which suppresses macro autophagy. by suppressing the complex that makes both the phagophore and the marker protein
207
How is macro autophagy affa]ected in fasting state?
starvation or rapamycin suppress mTOR which then does not suppress the complex which makes the phagophore and the marker protein which make up the autophagosome
208
What is a phagophore?
precursor to the autophagosome
209
List the steps and intermediates for the autophagosome marker protein synthesis
Pro-LC3 hydrolyzed by Atg4 to LC3-I which goes through lipidation via Atg7 and addition of phosphotidyl ethanolamine via Atg3 to become LC3-II and incorporate with phagophore to make autophagosome
210
What is the importance of Autophagy?
macromolecular disposal of waste, removal of defective organelles, removal of aggregates, back up to UPS, responsive to cellular stress
211
What are some clinical disorders associated with autophagy suppression?
neoplasia esp in liver, neurodegenerative ex parkinsons, responses to toxins ex alcohol and acetaminophen)
212
Where does UPS take place?
cytososl
213
What enzyme ubiquitylates a protein marking it for degradation?
E1: activating, E2 conjugating, E3 Ligase
214
What protein recognizes ubiquityn on protein and pulls it in for degradation and removes the ubiquitin?
19s regulatory complex on 26s proteasome
215
What part of and what enzyme degrade a ubiquitylated protein?
20s catalytic core or 20s proteasome of the 26s proteasome
216
Name the protein substrates degraded by the UPS.
regulatory proteins, transcription factors, damaged proteins, metabolic enzymes, antigens (75-80% intracellular proteins)
217
What things regulate the UPS and how?
cytokines up, sepsis up, trauma up, Alzheimer's and ND diseases fails or down, enhanced level of altered proteins up or down
218
How can UPS be targeted therapeutically?
anticancer drugs, anti-inflammatory compounds
219
What enzyme and where is the first metabolic step of ethanol ?
gastric lining, Gastric Alcohol dehydrogenase (ADH) ethanol-> acetaldehyde, men more than women,
220
What hepatic enzyme metabolizes ethanol in cytosol?
cytosolic ADH, reduce NAD to NADH to get acetaldehyde
221
What hepatic enzyme metabolizes ethanol in microsome (R)
microsomal cytochrome P450 2E1 (CYP2E1), oxidizes NADPH to NADP and H2O to intermediate the hydrolysis to acetaldehyde (big in brain)
222
What hepatic enzyme metabolizes ethanol in peroxisomes?
Peroxisomal Catalase H2O2 to H2O to get acetaldehyde
223
What hepatic enzyme metabolizes acetaldehyde in the mitochondria?
Mitochondrial aldehyde dehydrogenase (ALDH) reduce NAD to NADH to get acetic acid, some Asians are deficient in this.
224
what are some consequences of chronic ethanol metabolism?
altered redox (increased NADH/NAD), metabolic acidosis (lactate production increase due to NADH increase), enhanced lipogenesis (higher levels of NADH increase NADPH which participates in fatty acid synth.), mitochondrial dysfunction (NADH enhances ETS, elevates leakage of reactive O2-, cause lipid eroxide formationas MDA and 4-HNE), Inhibition of mitochondrial fatty acid oxidation (FA accum, esterifies to TriG), Metabolically derived acetaldehyde forms covalent adducts to protein lipids and DNA, or MDA->MAA)
225
Name 2 major non-oxidative metabolism paths for ethanol.
FAEE synthase to fatty acid ethyl ester (disrupts mitochondrial funct.), Phospholipase D to phosphotidylethanol (interferes w/ PLD dependent signaling)
226
How is acetaminophen metabolized?
conjugated to either glucuronide or sulfide= nontoxic or if overdosed metabolized with P450 2E1 to NAPQI which is toxic
227
what do you give to counteract acetaminophen overdose? how does it work?
NAC which is changed to GSH (depleted antioxidant) which helps change NAPQI to cysteine and mercapturic acid conjugate
228
why is ethanol excess bad with Tylenol ingestion?
ethanol increases the rate at which acetaminophen is metabolized by CYP2E1 by inducing it in the first place, forms NAPQI causes 70% depletion of GSH and forms adducts = cell death
229
Ethylene glycol is metabolized how?
ADH to glycoaldehyde ALDH to Glycolic acid --> oxalic acid
230
What blocks metabolism of ethylene glycol at what step and why?
ethanol, ADH, 100X higher affinity
231
How does methanol metabolize?
ADH to fomaldehyde, ALDH to formic acid folate to CO2 H2O
232
What does formic acid damage? What do you give to prevent formic acid from forming?
optic nerve, bicarbonate offset acidosis, or ethanol or fomepizole to compete with ADH
233
what are chaperones?
assist or mediate folding and assembly of prtoeins, anneal un/misfolded proteins and allow them to find their naitive state
234
Name some examples of chaperones.
HSP, GroEL &GroES, Protein disulfide isomerases, peptidylprolyl cis/trans isomerase
235
Alzheimer'shas what types of protein misfolding and why?
B-amyloid plaques, cleavage by gama-secretase within membrane spaning domain creates B-amyloid fragment, hydrophobic regions seek each other and form a plaque also form salt bridge
236
How do plaques effect brain in Alzheimer's?
build up in mitochondria and inhibit enzyme funct. and block utilization of glucose, fibrils dirupt Ca2+ homeostasis = apoptosis
237
What protein problem occurs in Huntingtons and why?
trinucleotide repeat, CAG, codon for glutamine (Q), poly Q region, amount of repeat effects classification of disease, destroys parts of brain controlling movement, emotion, and cognitive ability
238
what causes CAG repeats?
repair strand breaks and remove mispaired bases, often ubiquilated forming aggregates but not degrading suggests problem with proteasome, cross link or polar zipper formation
239
What is Parkinsons?
progressive degenerative dopaminergic projection from substantia nigra pars compacta (SNpc) to striatum
240
Pheotype of Parkinson's is...
motor dysfunctions resting tremors, postural instability, bradykinesia
241
What are factors that appear to play a role in Parkinsons
lack of dopamine, low norepinephrine, environmental triggers (toxins or viruses), genes LRRK-2 or a-synuclein or presence of lewy bodies
242
What role might a-synuclein play in parkinsons?
block ER-Golgi transport, ER stress and Golgi fragmentation, decrease synaptic vesicle relase, impaired energy production-> apoptosis induction, accumulation of CMA substrates -> proteasome impairment
243
How do prions infect and spread?
prion protein (PrPc) is affected by infectious isoform PrPsc changing PrPc to PrPsc with interaction. chain reaction, aggregation of isoform form amyloid fibers which form plaques
244
How does sickle cell anemia work?
mutant for of hemoglobin when deoxygenated can polymerize in to elongated rope like fiber connection hydrophobic btwn B subunits
245
What happens in Cystic fibrosis?
most common mutation of single codon 3nt deletion, phenylalanine deleted, protein fails to fold properly in ER, degraded before reaching surface, upsets NaCl balance needed to maintain normal mucus layer. mucus thick so bacteria and virus stick.
246
What receptor mutation causes immunity to m-tropic HIV if homozygous?
CCR5
