Term
|
Definition
| ORC complex binds to origin -> MCM complex binds to the ORC complex -> helicase binds to ORC/MCM complex and separates the DNA strands -> Single Strand Binding Proteins (SSBs), such as RPA, keep the strands apart |
|
|
Term
|
Definition
| separates the DNA strands and unwinds the parental duplex (uses energy of ATP hydrolysis) |
|
|
Term
|
Definition
| relieves the supercoiling of DNA by unwinding (breaks phosphodiester bonds and rejoins them) |
|
|
Term
|
Definition
| cyclic process of growth of a polypeptide chain from mRNA attached to ribosomes. Requires mRNA, ribosomes, activated aminoacyl-tRNA, elongation factor EF-Tu activated with GTP. |
|
|
Term
|
Definition
| Pols alpha, delta (lagging strand synthesis), epsilon (leading strand synthesis) |
|
|
Term
|
Definition
| RNA primer added upstream (3’ OH group) |
|
|
Term
|
Definition
| adds RNA primase with RNA polymerase allowing for RCF to bind, recruit PCNA which binds to DNA polymerase |
|
|
Term
| RCF (Replication Factor C) |
|
Definition
| clamp loader protein in elongation |
|
|
Term
| PCNA (Proliferating Cell Nuclear Antigen) |
|
Definition
| sliding clamp that increases the processivity of the polymerase allowing for it to stay attached to DNA longer |
|
|
Term
|
Definition
| removes the RNA primer from the 5’ end of Okazaki fragment |
|
|
Term
|
Definition
| process the 5’ end of Okazaki fragment to allow for ligation |
|
|
Term
|
Definition
| joins the 5’ phosphate end of one new DNA fragment to the adjacent 3’ hydroxyl end of the next. |
|
|
Term
| Polymerases that bypass areas of damaged DNA, Lack 5’ exonuclease activity |
|
Definition
| Pols κ, η, ξ, ι “Bypass polymerases” (Kappa, eta, ksi, iota) |
|
|
Term
| Polymerases responsible for DNA repair and replication |
|
Definition
| Pols α, δ, ε (alpha, delta, epsilon) |
|
|
Term
|
Definition
-A reverse transcriptase
-Mediates the repair or preservation of telomere regions (terminal sequences) of chromosomes
-binds to end of template strand, extends the template so you’re not losing any information
-RNA-dependent DNA polymerase
-contains both proteins and RNA template
-acts as a die for the repeating sequence of bases (TTAGGG) |
|
|
Term
|
Definition
| A 5' to 3' strand that is continuously formed by DNAP (DNA Polymerase) as it moves along the 3' to 5' strand |
|
|
Term
|
Definition
| A 3' to 5' strand formed by DNAP from the 5' to 3' strand. Is discontinuous, lagging, and retrograde (backwards). Replicated in short segments (Okazaki fragments) |
|
|
Term
| How does DNA Polymerase solve the Polarity problem of DNA Replication? |
|
Definition
| DNA polymerases can only add nucleotides to the 3’ end thus requiring the polymerases to move in opposite directions to make the two new strands. |
|
|
Term
|
Definition
| Mutation caused by depurination or deanimation |
|
|
Term
|
Definition
| Permanent changes in the DNA that can be inherited from germ cell or environmental. May have an effect on gene or gene product (proteins) |
|
|
Term
|
Definition
- Does not break the phosphodiester backbone
- causes the loss of a nitrogenous base: guanine or adenine
-results in a nucleotide deletion on new strand when replicated. |
|
|
Term
|
Definition
-Doesn't break phosphodiester backbone
-cytosine -> uracil
-replaces the C-G to U-A in one of the new strands |
|
|
Term
|
Definition
-Excites water in the cell forming hydroxyl radicals.
-breaks double strand |
|
|
Term
|
Definition
Causes CC-TT mutation
which makes Thymine Dimers |
|
|
Term
|
Definition
When oxidized by cytochrome P450, forms "bulky adducts" with guanine residues in DNA.
Highly mutagenic. |
|
|
Term
|
Definition
-A mutation that causes a change in a single nucleotide in the DNA sequence.
-Includes Missense, Nonsense, Insertion, Deletion. |
|
|
Term
|
Definition
Substitues one base for another (i.e Adenine to Cytosine).
Results in a codon that codes for a different AA (Amino Acid) |
|
|
Term
|
Definition
| Substitutes one base for another that results in a premature stop codon |
|
|
Term
|
Definition
-Adds extra nucleotide to DNA
-Can result in a frameshift mutation |
|
|
Term
|
Definition
-Removes a nucleotide from DNA strand
-Can result in a frameshift mutation |
|
|
Term
|
Definition
-slippage during DNA replication,
-formation of a kink
-re-anneals in wrong location, creating duplication of that region |
|
|
Term
|
Definition
- Has >40 CAG repeats (glutamine repeats)
-Caused by trinucleotide expansion of the gene that codes for Huntingtin* Protein.
*This is the correct spelling
**Repeat CAG <28 is normal. |
|
|
Term
| Chromosomal Translocation |
|
Definition
-results from breaks in chromosomes
- free ends of DNA at the break point reseal with the free ends of a different broken chromosome
- Often seen in Cancer cells |
|
|
Term
| Nucleotide excision repair |
|
Definition
| Used for the removal of thymine dimers and bulky adducts |
|
|
Term
| Dysfunction repaired by Nucleotide excision repair |
|
Definition
- Xeroderma Pigmentosum-> thymine dimers
- Benzo[a]pyrene --> "bulky adducts" |
|
|
Term
|
Definition
| Used to correct spontaneous mutations introduced during replication (due to Deanimations and Depurinations) |
|
|
Term
|
Definition
| Fixes incorrect DNA Base pairs (A-G, C-T) that are due to replication error |
|
|
Term
| Dysfunction repaired by Mismatch Repair |
|
Definition
- Hereditary Nonpolyposis Colorectal Cancer (lynch syndrome)
- Problems in MSH6,MSH2, MLH1 |
|
|
Term
| Non-homologous end joining (NHEJ) |
|
Definition
- "Quick and Dirty" repair mechanism
-Commonly used by cells in the G1 phase -Repairs double Strand breaks caused by ionizing radiation(xray, radioactive materials)
- may cause mutations (cause it loses some nucleotides)
-Ku7010 recognizes the double strand break |
|
|
Term
|
Definition
-repairs double strand breaks.
-Error free
-Can’t occur in G1, Must occur after replication (G2, M)
-Must have sister chromatids |
|
|
Term
| HNPCC or Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) |
|
Definition
-Due to mutations in either MLH1 or MSH2. Cells are unable to repair nucleotide mismatches.
-Increases risk of cancer in many tissues.
"L"ynch "S"yndrome has mutations in M"L"H1 or M"S"H2 |
|
|
Term
| Genes repaired by Homogulous Recombination |
|
Definition
-Brca2, ATM
-ATM phosphorylates p53 |
|
|
Term
|
Definition
- mutation in ATM
- affects both double strand repair (nonhomologous end joining and homologous combination)
-susceptible to agents that cause double stranded breaks in DNA: X-rays, Radiation therapy, Radiomimetic agents |
|
|
Term
|
Definition
-mutations a XP gene (XPA, XPB, XPC, XPD).
-Cause defect in nucleotide excision repair
-Inability to remove UV-damaged bases results in the accumulation of Thymine Dymers
-Highly photosensitive.
-Pigmented growths on the skin.
-High risk of skin cancer. |
|
|
Term
| Prokaryotic RNA Transcription Initiation |
|
Definition
-promoter region: -10 and -35
-operon: multiple genes
-core enzyme (aBB’w)
-holoenzyme: core enzyme + sigma factor
-Holoenzyme binds to promoter sequence ->RNA polymerase attaches and unwinds DNA |
|
|
Term
| Prokaryotic RNA Transcription Elongation |
|
Definition
-RNA made in 5’ to 3’ direction.
-After about 10 nucleotides, sigma factor releases cause RNA polymerase to transcribe faster |
|
|
Term
| Prokaryotic RNA Transcription Termination |
|
Definition
-Rho-independent: hair pin structure (GC rich) followed by 8 Uridine bases will disrupt RNA polymerase.
-Rho-dependent: Rho protein follows polymerase until it catches up at termination sequence and disrupts it. |
|
|
Term
| Prokaryotic RNA Transcription Transcription Inhibitors |
|
Definition
|
|
Term
|
Definition
| treats Tb by binding to beta subunit of RNA polymerase |
|
|
Term
|
Definition
binds sigma factor of RNAP
tx. for c. difficile |
|
|
Term
| Eukaryotic Transcription Initiation |
|
Definition
-promotor –TATA box
-transcriptional start site: +1
-one gene: exon and introns
-General transcription factors (TFII A, B,D,E,F, H): always used by RNA polymerase II
-Regulatory transcription factors: specific to genes or subset of genes.
-TBP binds TATA, recruiting TFIID
-RNA polymerase II is recruited to promotor
-TFIIH opens DNA helix -> phosphorylates polymerase II tail leading to release of GTF and polymerase moves into elongation stage |
|
|
Term
|
Definition
| Identify start site through the TATA box |
|
|
Term
|
Definition
| lead to diseases linked to DNA repair disorders (X. pigmentosa, Cockanye syndrome, Trichothiodystrophy) |
|
|
Term
|
Definition
-found in death cap mushroom
-binds to RNA polymerase II |
|
|
Term
| Eukaryotic Transcription: Elongation |
|
Definition
-RNA processing is regulated by the CTD of polymerase II
+processing of the CTD by TFIIH regulates RNA processing
-mRNA is 5’ capped, spliced, poly-a tail during transcription
-Spliceosome
-snRNA -> snRNA + protein = snRNP -> snRNP’s = Spliceosome
-5’ cap added after about 25 nucleotides
-Donor site binds with adenosine residue in intron, attacks acceptor breaking off lariat |
|
|
Term
| What happens to intron in Mutation of splice donor during transcription? |
|
Definition
|
|
Term
| Mutation of splice acceptor causes? (during Eukaryotic transcription) |
|
Definition
splice exon and intron (skip the acceptor, go to next)
+cystic fibrosis
+B-thalassemia: mutation destroys or create splice sites |
|
|
Term
| Eukaryotic Transciption: Termination |
|
Definition
-RNA polymerase will encode AAUAAA.
-Cleavage stimulation factor and CPSF transfers to RNA sequence
-Cleavage of 3’ end
-Addition of poly-a tail by PAP
-Binding of PABP to Poly-A tail |
|
|
Term
| Prokaryote Regulation of Transcription |
|
Definition
-Interchangeable RNS polymerase subunits
+sigma factors have different affinity for various promoters
-Genetic Switches
+factors that turn genes on and off (Lac operon) |
|
|
Term
| Eukaryote Regulation of Transcription |
|
Definition
-Modification of chromatin
-DNA methylation |
|
|
Term
| covalent histone modifications |
|
Definition
| -histones are positively charged -> the more acytelation the more negative the charge -> the looser the interaction, the more gene expression |
|
|
Term
| Rubinstein-Taybi syndrome |
|
Definition
-histone acytylation
-EP300 and CREBBP genes
-intellectual disability, facial features microcephaly |
|
|
Term
|
Definition
- prevents the turning off of genes
-inhibitor of histone deactylases (HDAC)
-chemotherapeutic possibly
-triggering gene expression causing cell apoptosis
-Epilepsy and Bipolar |
|
|
Term
|
Definition
- prevents the turning off of genes
-inhibits histone deactylates (HDACS)
-T-cell lymphoma
-binds zinc molecules |
|
|
Term
|
Definition
| Nucleosome removal, replacement, remodeling |
|
|
Term
|
Definition
-CHD7 gene
-Heart defects, atresia of choanae, retardation of growth, genital underdevelopment, ear abnormalities |
|
|
Term
|
Definition
+GC rich sequences exist in the promoter region
+cytosine is methylated to produce 5-methycytosine thus reducing ability of transcription factors to bind |
|
|
Term
|
Definition
-MECP2 gene
-intellectual disability, repetitive hand movements |
|
|
Term
|
Definition
-CGG repeats
-FMR1 gene; increase mythalation, decrease transcription
-Intellectual disability, ADD-like, prominent jaw, large ears |
|
|
Term
|
Definition
| RNA’s that can act as transcription factors |
|
|
Term
|
Definition
Diseases associated include brachydactyly, type d and syndactyly, type v
important for early development of metatarsals and metacarpals |
|
|
Term
| Nuclear receptors as transcription factor |
|
Definition
| will bind a specific sequence regulating gene: Tamoxifen |
|
|
Term
|
Definition
inhibits receptors (SERM) ability to act on DNA
Tx for breast cancer |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Codons grouped: read in 3 different frames. AUG determines the correct frame |
|
|
Term
|
Definition
-multiple proteins + rRNAs
-prokaryote: 70, 50, 30
-eukaryote: 80, 60, 40 |
|
|
Term
|
Definition
-transport amino acids
-adapter molecule necessary for recognizing the codon on the mRNA
-anticodon is going to complementary to our codon
-aminoacyl tRNA synthetase: covalently attaches the amino acid to the tRNA (20 different) |
|
|
Term
| What is need for translation? |
|
Definition
-Ribosomes
-Aminoacyl tRNA
-Translation Factors (facilitate process)
-mRNA (transported to cytoplasm) |
|
|
Term
|
Definition
-more than 1 tRNA for many of the amino acids
-some tRNAs can base pair with multiple codons, first 2 bases = wobble-base pairing |
|
|
Term
|
Definition
-AUG is the start codon for both eukaryotes and prokaryotes
-In prokaryotes, the methionine contains a formyl group. Only used at start. |
|
|
Term
| Prokaryote Translation Differences |
|
Definition
-mRNA encode operons
-Do not have 5’ cap or poly A tail
-each gene has an individual ribosome-binding site, start codon and termination codon |
|
|
Term
| Prokaryotic Translation Initiation |
|
Definition
-Shine Dalgarno sequence: ribosome binding site upstream from AUG
-IF-1 (binds 30s), IF-2 (binds tRNA), IF-3 (stabilizes 30s) |
|
|
Term
| Prokaryotic Translation Elongation |
|
Definition
1. tRNA binding
2. Peptide bond formation
3. Large subunit translocation
4. Small subunit translocation
-same in prokaryotes and eukaryotes |
|
|
Term
|
Definition
EF-Tu: escorts aminoacyl-tRNA to the ribosome in the A-site
Ribosome: catalyzes the peptide bond formation transferring to P-site
EF-G: binds ribosome to facilitate translocation of ribosome subunits |
|
|
Term
| Prokaryotic Translation Termination |
|
Definition
-stop codon: UAA, UAG, UGA
-release factor (RF1 or RF2) bind the A-site cleaving peptide chain or protein and fall apart by the RRF (ribosomal releasing factor) |
|
|
Term
| Eukaryote Translation Unique |
|
Definition
| -5’ methylated cap and poly-A tail |
|
|
Term
| Eukaryote Translation Initiation Factors |
|
Definition
Ternary complex
+eIF2: binds the initiator tRNA
Recruitment
+eIF4E: binds the 5’ cap
+eIF4A: helicase that unwinds the secondary structure |
|
|
Term
| Eukaryote Translation Elongation |
|
Definition
-eEF-1: escorts aminoacyl-tRNA to the ribosome in the A-site
-Ribsome: catalyzes peptide bond formation to the P-site
-eEF-2: binds the ribosome to facilitate translocation to the E-site |
|
|
Term
| Eukaryote Translation Termination |
|
Definition
Stop codons: UAA, UAG, UGA
-release factor (eRF1 or eRF2) bind the A-site joined by eRF3 cleaves the polypeptide from the aminoacyl-tRNA |
|
|
Term
|
Definition
ribosome will be continued to be recruited by eIF4F and due to space ribosome can be placed every 100 nucleotides. More ribosomes bound, more efficient.
Found on ER Surface |
|
|
Term
| Inhibitors of Translation |
|
Definition
1. Antibiotics: inhibitors of prokaryotic translation and bind directly to the ribosome
2. Macrolides: binds 50s and prevents the movement of tRNA from A site to P site
3. Chemotherapeutics: translation possible cancer treatment site. Targets for eIF4E, eIF4A |
|
|
Term
|
Definition
| binds 30s ribosomal subunit blocking the aminoacyl-tRNA from the A site |
|
|
Term
|
Definition
| binds 50s blocking the amino acid of the aminoacyl-tRNA in the A site inhibiting peptidyltransferase (very toxic) |
|
|
Term
|
Definition
| binds the 50s subunit at the P site blocking the very first tRNA |
|
|
Term
|
Definition
| binds isoleucyl tRNA synthetase preventing isoleucine from being attached to tRNA for transport to the ribosome |
|
|
Term
|
Definition
| binds the 30s ribosomal subunit blocking the initiation complex, cause misreading of the mRNA and ends translation prematurely |
|
|
Term
|
Definition
| inhibits Eukaryotic translation: addition of ADP-ribose to eEF2, leading to cell death |
|
|
Term
|
Definition
| isolated from castor beans, binds and removes an adenine residue from 60s making the ribosome inactive |
|
|
Term
|
Definition
| targeting translation factors: inhibits eIF4E |
|
|
Term
|
Definition
| using different combinations of splices sites to allow for production of different isoforms from the same gene |
|
|
Term
|
Definition
| variations of a protein with slightly different functions |
|
|
Term
|
Definition
| Intron retention, leaving in one of the intron |
|
|
Term
|
Definition
| Exon Skipping, exclude exon (different than mutation because has a function) |
|
|
Term
|
Definition
| Mutually Exclusive Exons: can have exon 2 or 3 but never both |
|
|
Term
|
Definition
| Alternative Polyadenylation: poly-a tail in intron or exon |
|
|
Term
| Translation control in stressful conditions |
|
Definition
decrease translation by phosphorylation of eIF2
eIF2 with GDP -> binds to eIF2B -> can’t get to GTP thus no translation on EIF2 |
|
|
Term
|
Definition
| decrease in growth factors, nutrients, infection, temperature |
|
|
Term
|
Definition
| progressive disease with mutation in eIF2B |
|
|
Term
| Iron regulating specific mRNA translation |
|
Definition
| -Free iron is bound to ferritin for storage in the cell |
|
|
Term
| Iron Response Protein (IRP) |
|
Definition
Low iron, ferritin blocked results transferrin synthesis
High iron = Iron + IRP no transferrin synthesis, results ferritin synthesis |
|
|
Term
|
Definition
| binds iron for transport in and out of the cell |
|
|
Term
|
Definition
-short noncoding RNAs
-binding mRNA 5’ end either store or target for degradation
-degradation matches identically, degraded right away
-if matches kinda, its stored in P-bodies and eventually degraded |
|
|
Term
|
Definition
-cleavage and removal of amino acid residues in the protein
+start methionine
+removal of signal sequence
-ie: Proinsulin is cleaved to produce insulin and C-peptide. |
|
|
Term
|
Definition
-protein kinases are enzymes responsible for adding phosphate group to a protein
-phophatases are enzymes responsible for removing phosphate group
-residues: serine, threonine |
|
|
Term
|
Definition
-addition of oligosaccharides to proteins via a glycosidic bond to the hydroxyl or amine group of an amino acid side chain
-occurs in ER and golgi |
|
|
Term
| Methylation and Acetylation |
|
Definition
| -actylation/methylation of histone tails at lysine and arginine |
|
|
Term
| Addition of Fatty Acids and Lipids to proteins |
|
Definition
-attach protein to membrane
-Myristoylation (glycine residue) and Palmitoylation (cysteine side chain) |
|
|
Term
|
Definition
| -addition of Hydroxyl group to amino acid (proline, lysine) |
|
|
Term
|
Definition
| mutations in the gene encoding lysyl hydroxylase…Super stretching/ brittle skin due to hydroxylation (collagen) |
|
|
Term
|
Definition
-carboxyl groups are added to glutamate residues
-blood clotting factors |
|
|
Term
|
Definition
| -addition of ubiquitin to a protein via a lysine residue to target proteins for degradation in the proteasome |
|
|
Term
| 3 modes of Protein Sorting |
|
Definition
| Gated Transport, Transmembrane transport, Vesicle Transport |
|
|
Term
|
Definition
| nuclear pore complex from cytosol to nucleus |
|
|
Term
|
Definition
| membrane bound protein translocators directly transport specific proteins across the membrane |
|
|
Term
|
Definition
| membrane enclose transport intermediates pinch off from other membrane-enclose compartments |
|
|
Term
|
Definition
| short sequence used to direct transports |
|
|
Term
| Hydrophobic Signal sequence |
|
Definition
|
|
Term
| Positive charge Signal sequence |
|
Definition
|
|
Term
|
Definition
| 3D arrangement of amino acids on proteins surface used for gated transport |
|
|
Term
|
Definition
| recognize signal sequences or patches |
|
|
Term
| Gated Transport - Transport to the Nucleus |
|
Definition
-histones, transcription factors, polymerases
-utilize nuclear pore complex: 50 proteins (nucleoporins)
-transport requires GTP |
|
|
Term
| Nuclear localization signal (NLS) |
|
Definition
- Facilitated transport through the nuclear pore
-positive charged amino acid binds to receptor -> receptor interacts with nucleoporins and chaperones the protein through the membrane |
|
|
Term
|
Definition
| translocase for outer membrane |
|
|
Term
|
Definition
| translocase for inner membrane |
|
|
Term
|
Definition
| translocase for inner membrane |
|
|
Term
| Transport to Mitochondria |
|
Definition
| requires ATP and H gradient |
|
|
Term
|
Definition
| increase in lactate levels and acidity (preventing pyruvate from entering TCA cycle) |
|
|
Term
| congenital lactic acidosis |
|
Definition
| mutation in the pyruvate dehydrogenase E1a subunit, reducing its transport to the mitochondria |
|
|
Term
| Congenital Lactic Acidosis Symptoms |
|
Definition
| loss of muscle tone, lethargy, vomiting |
|
|
Term
| Transport proteins to the ER |
|
Definition
-translocation into the ER is a co-translational process, it occurs while the protein is being synthesized
-The ER has an important role in posttranslational modifications
-Transmembrane proteins, proteins on lumen of ER, excreted proteins |
|
|
Term
| Free vs. Membrane Bound ribosomes |
|
Definition
-free ribosomes: remain in cytoplasm
-membrane-bound: start in cytoplasm and are recruited to the surface of ER |
|
|
Term
| Recruiting the Ribosome to ER |
|
Definition
-signal sequence (hydrophobic/nonpolar) ->
bind to signal recognition particle (SRP) ->
SRP has own receptor in the ER ->
receptor recruits to translocase channel (Sec61 complex) ->
ribosome sits on channel and translates directly into ER |
|
|
Term
| Translation of ER or secreted proteins |
|
Definition
| translation -> cleave signal sequence because it is hydrophobic, allowing the proteins to be free in the ER |
|
|
Term
| Creating Transmembrane protein |
|
Definition
| translation -> similar to translating soluble protein except with the addition of hydrophobic stop sequence disrupts sec61 protein and push ribosome off leaving the protein in the membrane |
|
|
Term
|
Definition
-job of chaperone proteins to aid in the folding of proteins
-ubiquitination only happens in cytosol, thus must be transported out of ER
not glycosylated properly, the protein is removed from the ER to be ubiquinated |
|
|
Term
| Unfolded protein response |
|
Definition
-Can’t fix unfolded proteins -> trigger cell death
-bombard ER with chaperone proteins to help with protein folding |
|
|
Term
| a-1-antitrypsin deficiency |
|
Definition
mutation in SERPINA1 that encodes a-1-antitrypsin
+leads to misfolding of the protein in the ER and activation of the unfolded protein response
disorder leads to emphysema in young adults and juvenile liver disease |
|
|
Term
| Where does glycolysation occur? |
|
Definition
Glycosylation occurs in ER and golgi
most proteins are glycosylated (N-glycosylation > O-glycosylation)
-oligosaccharide is synthesized in ER attached to Dolicol and transferred to the asparagine residue
-prior to folding in ER |
|
|
Term
|
Definition
| transfer to from ER, Golgi, lysosomes, endosomes, plasma membrane |
|
|
Term
|
Definition
All O-linked glycosylation occurs in the Gogli
Phosphorylation and Proteolysis as well |
|
|
Term
| Proteins associated with vesicle transport |
|
Definition
| Clathrin, COPI and COPII are proteins that bind the cytosol side of the vesicles used to transport proteins to/from/within the Golgi |
|
|
Term
|
Definition
| V-SNARES (vesicle) and t-SNARES (target membrane) interact catalyzing the fusion ot the two membranes. |
|
|
Term
| Tetanus and Botulism toxins |
|
Definition
| enter neurons and cleave SNARES |
|
|
Term
| Transport to the Lysosome |
|
Definition
| attachment of mannose 6-phosphate to a protein, targets the protein for the lysosome |
|
|
Term
|
Definition
deficiency in ability to phosphate mannose
skeletal abnormalities, restricted joint movement, coarse facial features, death by age 8 |
|
|
Term
| Secretory Vesicles: Golgi -> membrane |
|
Definition
-constitutive secretion: Golgi directly to membrane
-regulated secretion: secretory vesicles remain in cytoplasm until signal triggers fusion |
|
|
Term
|
Definition
during endocytosis
transport molecules bound to specific receptors for import into cell
-ie: cholesterol imported bound to LDL by binding to LDL receptor |
|
|
Term
| Familiar Hypercholesterolemia |
|
Definition
mutation in LDLR gene leading to LDL receptor deficiency leading to higher blood cholesterol levels
-symptoms include: xanthomas (accumulation of lipids under skin) |
|
|
Term
| Acidification of Endosome |
|
Definition
-pH is acidified in the endosome and lysosome by V-ATPase pump
-regulated by eNHE, which prevents hyperacidification
Exp: Christianson Syndrome |
|
|
Term
|
Definition
SLC9A6 gene affects Nervous system
symptoms: developmental delay, intellectual disability, inability to speak, ataxia, inability to walk, seizures |
|
|
Term
| Readily diffuses across lipid bilayer |
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Definition
| Nonpolar (Oxygen, CO2, Nitrogen) Polar (Water, Ethanol) |
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Term
| Can not diffuse across lipid bilayer |
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Definition
| Polar: Glucose, amino acids, Na+, K+, H+, Cl- |
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Term
| Ion Concentrations of Cell |
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Definition
Inside: High K+
Outside: High Na+, Cl- |
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Term
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Definition
| Regulation of Ca2+ Concentration, uses electrochemical gradient |
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Term
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Definition
uses energy
Regulation of Ca2+ Concentration |
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Term
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Definition
Regulates Na and K concentration
maintains the resting potential of the cell
keeps intracellular Na+ concentrations low
uses ATP
Transfers 3 Na+ out and 2 K+ in per cycle
net negative charge in the inner side of the plasma membrane |
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Term
| ATP-Binding Cassette Transporters (ABC) |
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Definition
-some are ion channels
-responsible for some forms of multidrug resistance:
ABCB1 (p-glycoprotein)
+drug comes in cell, and pump pushes right back out |
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Term
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Definition
CFTR: cystic fibrosis transmembrane conductance regulator
+CFTR regulated by both ATP and phosphorylation by PKA
+It is a Cl- transporter found in the plasma membrane, and can also transport bicarbonate (buffering) |
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Term
| Passive Transport (facilitated diffusion) |
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Definition
-molecules move down their concentration gradient from high-low
-does not require energy |
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Term
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Definition
-molecules move against their concentration gradient
-requires energy expenditure
-typically referred to as “pumps” |
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Term
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Definition
Form of active transport
-move two things at the same time
Symport: both things go in the same direction
Antiport: particles go in opposite direction |
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Term
| Na+ - Glucose symport (SGLT1: intestine and SGLT2: kidney) |
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Definition
Symport
glucose uses the electrochemical gradient of Na+ to go against concentration gradient |
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Term
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Definition
Symport
used to treat type 2 diabetes: limits glucose absorption |
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Term
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Definition
Antiport
3 Na+ moves in the cell, expels 2 Ca2+…regulating Ca levlels |
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Term
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Definition
Form of active transport
Use ATP to move molecules against gradient |
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Term
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Definition
Form of active transport
Uses the energy of absorbed photons of light to transport a solute against its electrochemical gradient. |
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Term
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Definition
not just charge, but concentration!!!
net force driving a charged solute across a membrane
Two components:
+concentration gradient of solute
+voltage across the membrane |
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Term
| Voltage-gated Ion Channel |
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Definition
Important for propagating electrical signals in nerve cells
Opening of voltage-gated ion channels is controlled by membrane potential
Change produces conformation change in channel opening or closing |
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Term
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Definition
| creation and propagation of action potential |
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Term
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Definition
| muscle excitation and contraction |
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Term
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Definition
| repolarization following action potential |
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Term
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Definition
| Ligand binding site (intracellular or extracellular) opens the channel |
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Term
| Nicotinic Acetycholine Receptor (nAChR) |
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Definition
Ligand-gated Ion Channel
transfers Na+ when acetylcholine binds |
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Term
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Definition
Stress-gated Ion Channel
stereocilia bend, opening the stress gated ion channel, allow ions to flow into the hair cells |
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Term
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Definition
| Voltage gated channel: allows Ca into neuron -> neurotransmitter released -> Ligand-gated ion channel allows Na into cell |
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Term
| Resting Membrane Potential |
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Definition
Is -70 mv for all cells between inside and outside, including resting nerve cells
K leak channels allows a little K out of the cell generating charge |
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Term
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Definition
| depolarization followed by rapid repolarization, resulting in sequential voltage gate channels |
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Term
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Definition
has moving parts, transfers molecules from one side of the membrane to the other by changing its shape
-Lysosome: Proton pump. Mitochondria: Pyruvate in, ATP out. Cell: sugar, amino acid, Na+.
-State A: open outside. Step B: facing inside of cell
-Net effect is that solute will move down concentration gradient (High-Low)
-Glucose uniporter (GLUT) is a passive transporter |
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Term
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Definition
Forms hydrophilic pores in the membrane that allow passage of small molecules (ions)
-Non-gated channels: passive transport, pore is regulated by what it allows through
+aquaporin: water transport allows for fast response to change in osmolarity |
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Term
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Definition
a. Most durable
b. Enables cells to withstand mechanical stresses
c. Joins cells together through desmosome and hemidesmosomes
d. Cytoplamic: keratin (epithelia), Vimentin (connective), Neurofilaments (neuron)
e. Nuclear: nuclear lamins (all animal cell)
i. Gives structure of nucleus |
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Term
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Definition
a. Highway of cell: Molecular Motors
b. Composed of alpha (minus end facing centrosome near nucleus) and beta (plus end exposed) tubulin heterodimers
c. Present in nucleated cells and platelets in the blood
d. Dynamic stability due to GTP, only grow and shrink from beta (plus end)
Overtime become GDP, and shrink |
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Term
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Definition
targets microtubules, inhibits microtubule and frozen in mitosis, causing cells to die
(Taxanes: microtubule stabizers Paclitaxel)
(Vinca Alkaloids- microtubule depolymerizers Vinblastine, Vincristine |
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Term
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Definition
| stabilizes microtubules in neuronal axons prevent dynamic microtubules preventing growing/shrinking (polarize cell) |
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Term
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Definition
microtubule organizing center (MTOC)
In mitosis: creates mitotic spindle apparatus |
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Term
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Definition
hair like
1. 9+2
2. Motile
3. In axonemes, movement of ciliary dynein along adjacent microtubule doublets causes bending |
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Term
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Definition
| defective cilia in fallopian tube due to mutation in dynein |
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Term
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Definition
| one per cell, in humans only found on sperm |
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Term
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Definition
a. Present in all cells, key in cellular movemnt
b. Thin, flexible, linear, helix structure, polarity (like microtubules)
c. Subunits: G-actin
d. Filaments: F-actin
e. Allows for muscle contraction
g. Contractile bundles
h. Contractile ring during cell division which pinches off two daughter cell
i. Grow from one end (plus), and shrink from the other end (minus)
Contractile bundles |
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Term
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Definition
increase SA of the cell
Never motile |
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Term
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Definition
| toxin found in death cap mushroom, stabilizing actin |
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Term
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Definition
| fungal toxin, blocks polymerization |
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Term
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Definition
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Term
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Definition
Myosin- moves toward the plus end
Myosin in membrane: forces the actin molecule to move |
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Term
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Definition
Spectrin, Ankyrin, Band 4.1, Actin
only cytoskeleton structure units in erythrocytes |
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Term
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Definition
| erythrocyte becomes ball shape, and destroyed by spleen (anemia) |
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Term
| Describe how myosin thick filaments and actin thin filaments contribute to the process of muscle contraction. |
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Definition
myosin heads in thick filaments walk along the actin filaments (thin filaments) toward the plus end (associated with Z disc)
-produces shortening of the sarcomere (muscle contraction) |
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Term
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Definition
two regulatory proteins prevent myosin thick filaments from moving along the actin thin filaments
-Ca binds to tropomyosin, moving it, allowing for contraction |
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Term
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Definition
a. transport from plasma membrane to Golgi
b. Golgi to endosomes
c. Secretory vesicles to Golgi
d. Made up of subunits called triskelions
e. Require Dynamin (protein) to pinch off from the ER through GTP hydrolysis |
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Term
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Definition
| Retrograde transport from Golgi to ER |
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Term
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Definition
a. Transport from ER to cis Golgi
b. Sar1: membrane bound enzyme -> Sar1-GEF bind to Sar1 -> releasing GDP and bind GTP -> Sar1 exposes helix that inserts into ER membrane -> recruits Sec23, Sec24
c. Sec13 and Sec31 forms COPII coats
i. Fall off vesicle after release allowing vesicle to fuse
d. Travel along microtubules: Kinesin from ER to golgi
e. KDEL receptors: retrieval of ER Cargo receptors and Soluble ER proteins |
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Term
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Definition
proteins on the vesicle for the target membrane
Rab effectors bring the vesicle close enough to the target membrane to allow for v-SNARE and t-SNARE interactions that will mediate fusion
Ca is required to move v-snare and t-snare to fuse |
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Term
| Transport of Hydrolases to Lysosome |
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Definition
clathrin coat sends to lysosome by the addition of mannose-6-phosphate
I-cell disease: lysosomal storage disease |
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Term
| Receptor-Mediated Endocytosis |
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Definition
| ie: ferrotransferrin receptor -> clathrin coated vesicle -> removal of clathrin, naked vesicle -> fuse with endosome -> low pH causes release of Fe to cytosol -> fuse back with plasma membrane -> apotransferrin release |
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Term
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Definition
| glucose transporters are stored on the endosome that can be quickly released to the plasma membrane in a response to external stimuli |
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Term
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Definition
| make hormones -> package in secretory vesicles but have to wait for signal |
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Term
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Definition
| beta cells in Islets make insulin ->high glucose goes in mitochondria that produces ATP closing ATP-sensitive potassium on the plasma membrane resulting in a depolarization of membrane -> opens up voltage gate Ca channel -> induces release of insulin |
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Term
| Two major types of Extra Cellular Matrix |
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Definition
ECM associated with epithelial tissue - like Basal Lamina
ECM associated with connective tissue |
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Term
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Definition
muscle cells surrounded by basal lamina
-Major components
-laminin: alpha, beta and gamma subunits with 4 arms
-type IV collagen |
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Term
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Definition
composed of alpha chains -> collagen fibrils -> collagen fibers (triple a helix)
produced by Fibroblasts (skin/tendon), Osteoblasts (bone) |
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Term
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Definition
1. Fibrillar: Type 1 form layers reinforced by calcium in bones
2. Sheet-forming
3. Anchoring/Linking |
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Term
| formation of fibrillar collagen (Golgi) |
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Definition
| hydroxylation on prolines and lysines -> glycoslation of hydoxylysines -> cleavage of proteases |
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Term
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Definition
characterized by brittle bones
Type 1 is most prevalent (Fibrillar) |
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Term
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Definition
stretchy skin, hyper-flexible joints
Type 6 is due to a mutation in the gene encoding lysyl hydroxylase |
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Term
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Definition
large glycoprotein: two subunits joined by disulfide bonds
-provides cells a linkage to the collagen fibrils in the ECM through its interactions with integrals |
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Term
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Definition
Take up a lot of space, fill most of the extracellular space
Four main groups:Hyaluronan, Chrondroitin sulfate, Heparan sulfate, Keratan sulfate
highly hydrophilic |
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Term
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Definition
| simplest GAG, only GAG not linked to a core protein and therefore is not synthesized in the ER. Synthesis on plasma membrane |
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Term
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Definition
| Size contributes to function |
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Term
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Definition
| Huge. Major component of cartilage |
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Term
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Definition
| Aggrecan + Hyaluronan: resists compressive forces (synovial fluid) |
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Term
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Definition
| Small. Binds to collagen fibrils and regulates fibril assembly |
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Term
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Definition
plasma membrane proteoglycan
-found on fibroblasts: produces signal inside the cell
-ie: Betaglycan: Binds to TGFB and presents it to TGFB receptors |
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Term
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Definition
loose/unstructured polypeptide chains that are covalently cross-linked
-allow (connective tissue of muscle, blood vessels, skin, lungs) to stretch and relax
-collagen fibers are interwoven to prevent tears |
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Term
| Two main components that make up elastic fibers |
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Definition
1.Elastin
2.Microfibrils
a.Polymers composed of the glycoprotein Fibrillin |
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Term
| a-1 antitrypsin deficiency |
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Definition
a-1 antitrypsin is a protease by the liver that inhibits neutrophil elastase (enzyme that cleaves elastin)
since no a-1 antitrypsin, elastin is destroyed limiting the elasticity giving rise to emphysema or COPD
ie: someone that smokes: neutrophils are recruited and chews up elastin |
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Term
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Definition
disorder of connective tissue
mutation of fibrillin-1 gene: won’t produce microfibrils in elastic fibers
aorta and ligaments most severe effects: can’t retract
very tall and long limbs |
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Term
| Matrix Metalloproteinases (MMPs) |
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Definition
major class of enzymes that degrade
require Ca or Zn
each one has a specific target substrate
Strictly regulated
degradation important for cell migration and growth |
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Term
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Definition
Regulates MMP's
proteases secreted as inactive precursors that can be activated locally when needed
a. Plasminogen: cleaved to produce plasmin that helps break up clots |
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Term
| confinement by cell surface receptors |
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Definition
MMP Regulator
many cells have receptors that bind proteases, confining the enzyme to the sites
a. Urokinas-type plasminogen activator (uPA): bind enzyme to metastasize in cancer |
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Term
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Definition
MMP Regulator
Tissue inhibitors of MetalloProteinases (TIMPs)
i. Bind tightly to activated MMPs and block activity |
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Term
| ECM degradation and Cancer |
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Definition
| able to produce MMPs to break up the collagen-filled ECM, allowing the cell to invade the tissue |
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Term
| Calcium-independent cell adhesion molecules |
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Definition
| Immunoglobulin-like (I-CAMS) |
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Term
| Immunoglobulin-like (I-CAMS) |
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Definition
a. Cell adhesion molecules that interact with either integrins or other I-CAMS
b. Immunoglobulin like in structure
c. N-CAMs (neural), VCAM (vascular), PECAM-1 (platelet) |
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Term
| Calcium-dependent Cell adhesion molecules |
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Definition
Cadherins
Integrins
Selectins |
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Term
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Definition
a. Cadherin repeats that bind to Ca
i.Binding of Ca to hing regions prevent molecule from flexing
b. E-Cadherin (epithelial), N-Cadherin (neural), P-Cadherin (placenta)
c. Components of adherens junctions and desmosome |
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Term
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Definition
Heterodimers (alpha and beta subunits)
Extracellular: Grabs onto the ECM and holds the cell in place
Intracellular: integrins connect to the actin filaments
Can initiate signal transduction |
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Term
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Definition
Cell surface carbohydrate-binding proteins
Creates a weak adhesion between cells: low affinity for glycans but binds to glycans through its lectin domain |
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Term
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Definition
Integrin Signal transduction
T-cell binds to antigen binding cell ->integrin clamps onto I-CAM that allows for the T-Cell receptor and antigen to bind -> receptor relays signal to integrin to bind more tightly to the I-CAM |
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Term
| Fibronectin-Integrin complex |
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Definition
| provides bridge between ECM and actin |
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Term
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Definition
1. Cadherin
2. Ig-like (I-CAMs)
3. Selectins |
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Term
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Definition
|
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Term
| hold the axon-dendrite synapse together |
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Definition
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Term
|
Definition
| movement from circulation to site of tissue damage or infection |
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Term
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Definition
1st step of leukocyte extravasation
+macrophages in affected tissue release cytokines to attract leukocytes inducing the expression of selectins on the surface of the endothelial cells lining the blood vessel |
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Term
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Definition
2nd step of leukocyte extravasation
+carbohydrates on leukocyte plasma membrane bind to selectins on plasma membrane |
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Term
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Definition
3rd step of leukocyte extravasation
Integrins on leukocytes bind to I-CAMs with high affinity immobilize leukocyte |
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Term
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Definition
4th step of leukocyte extravasation
leukocyte passage through gaps between endothelial cells is mediated by PECAMs |
|
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Term
| Steps of Leukocyte Extravastation |
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Definition
1. Chemo-attraction
2. Rolling Adhesion
3. Tight Adhesion
4. Transmigration |
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