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MCM > Exam 2 > Flashcards

Exam 2 Flashcards

1
Q

DNA base pairing

A

C-G ( 3 hydrogen bonds)

A-T (2 hydrogen bonds)

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2
Q

Viruses affect

A

Reverse transcription

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3
Q

Basic organization of genome

A

DNA double helix is wrapped around histone, which forms a nucleosome which is formed into chromatin, which is condensed into a chromosome

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4
Q

Chromatin

A

Protein + nuclear DNA

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5
Q

Heterochromatin

A

Chromatin that is very condensed and stains darkly

  • highly concentrated at centromeres and telomeres
  • genes are resistant to gene expression
  • will silence a gene that is position near it
  • transcriptionally inactive
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6
Q

Euchromatin

A

Less condensed, loosely packed, easily accessible chromatin

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7
Q

Position effect

A

Activity of a gene depends on position of chromosome

* gene will be silenced if positioned near heterochromatin

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8
Q

Salt linkages

A
  • Lysine and arginine
  • Histone acetylation
  • Histone methylation
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9
Q

Lysine and Arginine

A

positive charges that comprise more than 1/5 of histone residues; effectively neutralize negatively charged DNA backbone

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10
Q

Histone acetylation

A

Keep histone interaction loose - removes positive charge, allowing more transcription

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11
Q

Histone methylation

A

Keeps histone interaction loose- acts as a physical barrier, allows more transcription

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12
Q

Nucleosomes

A

Form “beads on a string” containing 8 histones

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13
Q

Human genome project

A

46 chromosomes: 2 copies of 23 chromosomes

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14
Q

Helicase

A

Unwinds DNA helix

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15
Q

Topoisomerase

A

Relieves overwound supercoils (think telephone cord) by breaking phosphodiester bond

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16
Q

Single-stranded DNA binding protein

A

Binds the single stranded DNA that has been separated

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17
Q

DNA polymerase

A

Synthesis new DNA chain in the 5’ -> 3’ direction, fills gaps, and synthesizes RNA-DNA primer

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18
Q

DNA ligase

A

Seals nicks

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19
Q

Replication fork

A

Synthesizes DNA in 5’ to 3’ direction (phosphoryl to hydroxyl)

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20
Q

Leading strand

A

Synthesized continuously

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21
Q

Lagging strand

A

Synthesized in segments known as Okazaki fragments

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22
Q

DNA primase

A

Synthesizes short RNA primers to initiate DNA replication

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23
Q

Nomenclature of bases

A

The building block of DNA is a deoxyribonucleotide composed of a 20deoxyribose with a base attached at the 1’ position and a phosphate attached at the 5’ position. A base plus a (deoxy)ribose yields a (deoxy)ribnucleoside. Thus, a (deoxy)ribonucleotide is a (deoxy)ribonucleosome with one to three phosphate groups

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24
Q

Nucleoside analog inhibitors

A

Cytosine araC: Because DNA synthesis involves the formation of 3’ to 5’ phosphodiester bonds, nucleoside analogues that lack the 3’ OH group act as drugs that inhibit replication, but must be converted to dNTPs before they can act to inhibit DNA polymerase. Ara-C contains the sugar arabinose, which is converted by animals into ara-CTP which is a potent competitive inhibitor of DNA polymerase and used to treat leukemia.

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25
Q

Spontaneous DNA damage

A
  • Depurination
  • Deamination

If unrepaired when DNA is replicated, these changes lead to either a deletion or a base pair substitution in the daughter strand

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26
Q

Depurination

A

Loss of a purine base via hydrolysis of the N-glycosyl linkage

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27
Q

Deamination

A

The amino group of a purine or pyrimidine base is hydrolyzed such that adenine is converted to hypoxanthine, guanine is converted to xanthine, and cytosine is converted to uracil, which forms an unnatural deoxyuride

  • A -> I
  • G -> X
  • C -> U
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28
Q

Nonionizing radiation

A

Ie. UV radiation, produces covalent linkage between two adjacent pyrimidines known as pyrimidine dimers (T-T or C-T)

  • pyrimidine cyclobutane dimers
  • 6-4 covalent linkage of pyrimidines
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29
Q

Ionizing radiation

A

Ie X-rays, reactive oxygen species produced cause direct strand breaks, DNA-protein cross-links, and 40-60 chemically distinct base damages

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30
Q

Thymine modifications

A
  • pyrimidine cyclobutane dimers
  • 6-4 covalent linkage of 2 pyrimidines

Caused by nonionzing radiation

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31
Q

Intercalation

A

Agents insert between stacked bases of the DNA double helix, causing some unwinding of the helix and separation of base pairs
- they are mutagenic and interfere with replication, repair processes, and transcription, and can also interfere with topoisomerase and cause strand breaks

(Ie. Ethidium bromide, thalidomide, doxorubicin, daunomycin)

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32
Q

Benzopyrenes

A

Can cause damage to DNA

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33
Q

Direct repair (enzymatic repair)

A

Pyrimidine dimers
O6-methylguanine

Enzymes: DNA photolyase and methylguanine transferase

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34
Q

Base excision repair (BER)

A

Single base mismatches, nondistorting alterations

Enzymes: DNA glycolases, AP endonuclease, AP lyase, DNA polymerase, DNA ligase

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35
Q

Nucleotide excision repair (NER)

A

Chemical adducts that distort DNA (pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts)

Enzymes: NER protein complex, DNA polymerase, DNA ligase

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36
Q

Xeroderma Pigmentosum

A

Associated disorder of nucleotide excision repair

Inherited disease where Skin is extremely sensitive to sunlight, causing pt to be prone to melanoma and squamous cell carcinoma

UV light causes cyclobutane thymine dimers to form in DNA which is easily repaired by NER, but those with defects in XP proteins in the NER complex exhibit the disease

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37
Q

Mismatch excision repair (MER)

A

Mismatched base in daughter strand

Enzyme: MER complex, helicase/endonuclease, DNA polymerase, DNA ligase

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38
Q

Hereditary nonpolyposis colorectal cancers

A

Associated disorder of Mismatch excision repair

Inherited disease with mutation of one of the alleles of genes in the MER complex results in increased susceptibility to HNC cancer

Mutation in both alleles would render the MER system nonfunctional and allow tumor development

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39
Q

Recombination repair

  • Nonhomologous end joining (NHEJ)
  • homologous recombination
A

Double-strand breaks, interstrand cross-linking

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40
Q

Nonhomologous end joining (NHEJ)

A

double-strand breaks, interstrand cross-linking

  • damaged ends filled in and joined; some base pairs may be missing. Multiple proteins and enzymes including DNA ligase
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41
Q

Homologous recombination

A

Double-strand breaks, interstrand cross-linking

  • Exonucleases, DNA polymerase, MER system, Damaged duplex repair using information on undamaged homologous duplex
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42
Q

BRCA1/2 breast cancer

A

Associated disorder of recombination repair: homologous recombination

BRCA 1 and 2 are tumor supressor genes. Mutations cause a fivefold increase in a woman’s chance of having breast and/or ovarian cancer before reaching menopause. Men with mutations also have an increased chance of developing breast cancer. Mutations in these genes also lead to increased risk of developing other cancers

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43
Q

Transcription-coupled repair (TCR)

A

Stalled RNA polymerase during transcription (not replication)

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44
Q

Cockayne syndrome

A

Associated disorder of Transcription-coupled repair

Rare autosomal recessive, congenital disorder involving mutant genes of ERCC6 and ERCC8 which code for proteins involved in TCR of DNA. If DNA is not repaired, cell dysfunction and cell death may occur.

S/S: developmental and neurological delay, photosensitivity, premature aging (progeria)

Death usually occurs in the first 2 decades of life

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45
Q

Translesion synthesis (bypass synthesis)

A

Unrepaired thymine dimers or apurini AP sites

DNA polymerases

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46
Q

Structure of RNA

A

Single stranded polymer of ribonuceotides, each consisting of base, pentose sugar and phosphate, that link via 3’-5’ phosphodiester bonds

  • more unstable than DNA
  • uses Uracil instead of thymine
  • can fold int 3-D structures
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47
Q

tRNA (transfer RNA)

A

15% of total cellular RNA
Metabolically stable
Carry amino acids to ribosomes for incorporation into growing polypeptide chains

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48
Q

Ribosomal RNA (rRNA)

A

Structural and functional (catalytic) component of ribosomes

Stable and long-lived

80%

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49
Q

Messenger RNA (mRNA)

A

Direct carrier of genetic information from genes to ribosomes for protein synthesis

Short-lived

1-5%

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50
Q

Small nuclear RNA (snRNA)

A

Direct the splicing of pre-mRNA to from mRNA

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51
Q

Small interfering RNA (siRNA)

A

Regulate eukaryotic gene expression by degrading select mRNA

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52
Q

Micro RNA (miRNA)

A

Regulate gene expression by blocking translation of selective mRNA

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53
Q

RNA polymerase I

A

Located in nucleolus

Catalyzes the synthesis of a single large precursor rRNA

(Makes ribosomal RNA)

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54
Q

RNA polymerase II

A

Located in the nucleoplasm

Catalyzes the synthesis of precursor mRNA, also synthesizes some snRNA and miRNA

(Makes messenger RNA)

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55
Q

RNA polymerase III

A

Located in nucleoplasm

Synthesis of tRNA and snRNA

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56
Q

Coding (sense) strand

A

Non-template strand, indentical to the sequence of RNA that will be produced

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57
Q

Transcription start site

A

+1 position of the gene that usually has an A or G. Site where the Basal transcription factors and the RNA polymerase bind

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58
Q

Transcription stop site

A

Poly A Tail (5’ - AATAAA - 3’) that is clipped off during RNA processing

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59
Q

Transcription unit

A

Linear sequence of DNA from start to stop site

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60
Q

Promoter

A

Sequence upstream of start site where basal transcription facts (initiation factors) bind and recruit the RNA polymerase

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61
Q

Enhancers/silencers

A

Short sequences present upstream, downstream, or in the transcription unit, and sites for binding of additional transcription factors that influence rate of transcription

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62
Q

Transcription

A
  1. Assembly of pre-initiation complex
  2. Elongation
  3. Termination
  • RNA polymerase binds to promoter on DNA
  • DNA double helix unwinds
  • One strand acts as a template for RNA synthesis and nucleotide sequence is determined by complementary base pairing that link by phosphodiester bonds
  • RNA polymerase catalyzes the reaction
  • RNA sequence is elongated in the 5’ to 3’ direction and released from the DNA as a single strand
  • RNA sequence is complementary to template and identical to coding strand
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63
Q

Initiation

A

TRIID is recognized by TBP binds to TATA box, TFIIB, TFIIF, RNA pol II, TFIIE, and TFIIH are recruited and join

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64
Q

Separation of DNA strands

A

TFIIH unwinds the DNA double helix and exposes the DNA template strand

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65
Q

Initiation of polymerization

A

RNA pol II can function in absence of a primer and catalyzes formation of a dinucleotide using DNA as a template, capping enzyme adds 7-methyl guanosine cap on the 5’ end

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66
Q

7-methyl guanosine cap

A

Protects against degradation and helps to bind mRNA to ribosome during translation, binds on 5’ end of mRNA with a 5’-5’ diphosphate linkage

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67
Q

Histone acetyl transferase (HAT)

A

Add acetyl group to histones, reduces positive charge and loosens interaction with DNA

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68
Q

Histone deacetylases (HDACs)

A

Add back the acetyl grp and reverse action of HAT

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69
Q

Elongation

A

Begins after formation of nascent RNA, RNA pol breaks interaction with promotor when the tail of RNA pol II is phosphorylated by TFIIH

Elongation generates superhelical tension that is eased by DNA gyrase

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70
Q

DNA gyrase

A

Eases superhelical tension caused by elongation

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71
Q

Termination

A

Transcription ends when RNA pol encounters termination signals on the DNA template, RNA transcript forms a self complementary hairpin followed by a poly U tail

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72
Q

mRNA processing

A
  • modification of the 5’ end of mRNA with the capping by 7-methyl guanosine
  • removal of introns or non-coding sequences by splicing
  • modification of the 3’ end of mRNA by polyadenation (poly A tail)
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73
Q

Transcription factors

A

Trans-acting proteins that regulate the transcription of genes across chromosomes. They have DNA-binding domains that enable them to bind to specific DNA sequences in the promoter or regulatory regions of genes. Transcription factors can either promote or repress the transcription of target genes. They bind as homo or heterodimers and recruit other proteins. Modulation of the activity of transcription factors usually involves phophorylation.

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74
Q

Homeodomain proteins

A

Contain a conserved 60 residue DNA biding motif or homeodomain

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75
Q

Zinc finger proteins

A

Have short regions containing Cys and His residues that interact with Zn ions that produce multiple loops or Zn fingers that insert into major grooves of DNA

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76
Q

Leucine zipper proteins

A

Contain DNA binding sequence where every 7th residue is Leu which promotes dimerization and coiling of these sequences

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77
Q

Basic Helix Loop Helix proteins

A

Similar to zipper proteins except alpha helical regions separated by non-helical loop space

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78
Q

Transcription factors and cancer

A

Inappropriate inactivation/activation of genes that control cell growth by deregulation of transcription factors may lead to cancer

  • mutated genes for TF’s represent a significant fraction of oncogenes
  • mis-regulation may occur by aberrant increase in expression or by mutations in the coding sequence that alters activity of TF
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79
Q

Abberant methylation of DNA

A

Fragile X mental retardation (FMR1)

  • FMR1 gene encodes for a protein with neurological function
  • DNA sequence has excessive (>200) copies of CGG (compared to nl of 30) which makes it susceptible to methylation of cytosine
  • FMR1 gene becomes silent even though triplet expansion is upstream of protein coding sequence
  • as methylation repeat region extends into the promoter region, transcription is turned off
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80
Q

Protein synthesis occurs on

A

Ribosomes

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81
Q

Which direction is a protein synthesized?

A

Amino to carboxyl (5’ to 3’)

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82
Q

Genetic code

A

Converts the nucleotide sequence of a gene into the amino acid sequence of a protein using mRNA as an intermediary

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83
Q

Codon

A

Group of 3 consecutive nucleotides in the RNA

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84
Q

Stop codon

A

There are 3

  • UAA
  • UAG
  • UGA
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85
Q

Start codon

A

AUG (methionine)

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86
Q

Mutations

A

Silent
Missense
Nonsense
Frameshift

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87
Q

Silent Mutation

A

Does not change the amino acid

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88
Q

Missense mutation

A

Changes the amino acid in the protein with either no effect on protein function of a protein with vastly different function

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89
Q

Nonsense mutation (null mutation)

A

Codon changes into a stop codon causing premature termination, protein either degraded or formed as a truncated version

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90
Q

Frameshift mutation

A

One or more nucleotides are deleted or inserted into ORF, if out of frame causes change in the codon sequence and consequently alteration in the amino acid sequence

Ie. Duchenne muscular dystrophy, beta thalassemia

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91
Q

How does a codon recognize an amino acid?

A

tRNA

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92
Q

Ribosomes and mRNA

A

A large ribosome subunit and small ribosome subunit assemble into an active ribosomal complex by the presence of mRNA. This complex has 3 important sites

  1. Acceptor (A) site
  2. Peptidyl (P) site
  3. Empty (E) site
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93
Q

Acceptor (A) site

A

Location where the mRNA codon is exposed and set to receive all aminoacyl-tRNAs except initiating methionine tRNA

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94
Q

Peptidyl (P) site

A

Location where the aminoacyl-tRNA is attached to the growing polypeptide chain

(Methionine initiator binds here to start things)

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95
Q

Empty (E) site

A

Location that the empty tRNA occupies just prior to exiting the ribosome

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96
Q

Aminoactyl tRNA’s

A

Activated forms of amino acids that are esterified to the 3’-OH group of the 3’ terminal adenine in the acceptor stem of their cognate tRNA

Catalyzed by enzymes called aminoacyl tRNA synthetases

  • when an amino acid is bound, the tRNA is said to be charged
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97
Q

Activation of amino acids

A

A two step process

  1. Aminoacyl tRNA synthetase catalyzes the activation of amino acid by transferring AMP to COOH end
  2. Transfers the amino acid for amino acid-AMP to cognate tRNA
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98
Q

Aminoacyl synthetases

A

Catalyze the activation process of tRNA charging

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99
Q

Translating an mRNA

A
  • tRNA binding
  • peptide bond formation
  • large subunit translocation
  • small subunit translocation
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100
Q

Mechanism of Translation

A
  1. Initiation
  2. Elongation
  3. Termination
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101
Q

Translation Initiation

A

Pre initiator complex is assembled, then large subunit is added to form initiation complex, initiator tRNA bound to GTP attaches to P site of small subunit, the initiator tRNA-methionine complex loads onto the small su on the P-site, other initiation factors are added, the large su is added, and translation begins with the initiation codon AUG (methionine)

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102
Q

Translation Elongation

A

Activated amino acid attached to initiating methionine via a peptide bond, GTP-bound aminoacyl tRNA is loaded to the A site via GTP hydrolysis (anticodon and codon of A site base pair), peptide bond is catalyzed by petidyl transferase

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103
Q

Translation Elongation Factors

A

Factors EF1 and EF 2 (EF-Tu and EF-G in bacteria) Proofread, making translation more efficient and accurate

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104
Q

Translation Termination

A

Peptide chain is released from ribosomal complex which then dissociates into its components, Termination is triggered by stop codons (UAA, UAG, UGA) which are recognized by release factors from the tRNA, Release factors bind to A site and cleave the ester bond between the C terminus of the polypeptide and the tRNA, The catalyzation of a H2O molecule instead of an amino acid then adds COOH to the end of the polypeptide

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105
Q

Streptomycin

A

Binds to the 30S ribosomal subunit in prokaryotes to disrupt the initiation of translation

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106
Q

Shiga toxin

A

Binds to the 60s subunit of eukaryotes to disrupt elongation

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107
Q

Clindamycin/Erythromycin

A

Binds to the 50S subunit in prokaryotes to disrupt translocation of the ribosomes

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108
Q

Tetracyclines

A

Bind to the 30S subunit in prokaryotes to disrupt elongation

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109
Q

Peptidyl transferase activity

A

Housed in the large subunits

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110
Q

Initiation factors

A

Facilitate bind of the small ribosomal subunit to the initiator tRNA and base pairing between the anitcodon and codon

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111
Q

Hydrolysis of GTP to GDP + Pi

A

Provides the energy for assembly of the initiation complex

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112
Q

elF4 complex and elF5B-GTP

A

Additional initiation factors required for the assembly of the final 80S initiation complex in eukaryotes

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113
Q

Polysomes

A

Clusters of 10-100 ribosomes attached simultaneously to a single mRNA molecule, each synthesizing a polypeptide chain and making protein synthesis more efficient

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114
Q

Protein sorting

A

Sites of protein synthesis depends on destination of protein

2 major pathways

  1. Cytoplasmic pathway
  2. Secretory pathway
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115
Q

Cytoplasmic pathway

A

For proteins destined for cytosol, mitochondria, nucleus, and peroxisomes

  • protein synthesis begins and ends on free ribosomes in cytoplasm
  • absence of presence of translocation signals play role in final targeting

** no translocation signals

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116
Q

Secretory pathway

A

For proteins destined for ER, lysosomes, plasma membranes, or for secretin

  • translation begins on free ribosomes but terminates on ribosomes sent to ER
  • proteins have ER targeting signal sequences present in the first amino acid residues of the polypeptide
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117
Q

Mitochondrial protein import

A

Cytoplasmic pathway

Proteins are passed across the mitochondrial membranes via translocator complexes TIM and TOM, unfolded proteins are protected by chaperones, specifically heat shock proteins 70

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118
Q

TIM

A

Transporter inner membrane

Helps bring proteins into mitochondria

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119
Q

TOM

A

Transporter outer membrane

Helps proteins pass across mitochondrial membrane

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120
Q

Heat Shock proteins 70 (HSP70)

A

Chaperone that protects unfolded proteins passing through the mitochondrial membranes

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121
Q

Nuclear localization signals

A

Cytoplasmic pathway

Utilized to imported large proteins into nuclear pores

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122
Q

Cytoplasm

Pathway and signal

A

Cytoplasmic Pathway

No signal

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123
Q

Mitochondria

pathway and signal

A

Cytoplasmic pathway

N-terminal hydrophobic alpha helix signal peptide

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124
Q

Nucleus

Pathway signal

A

Cytoplasmic pathway

KKKRK signal sequence

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125
Q

Peroximsomes

Pathway and Signal

A

Cytoplasmic pathway

C-terminal SKL signal sequence

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126
Q

ER lumen

Pathway and signal

A

Secretory pathway

C-terminal KDEL retention signal

And N-terminal hydrophobic alpha helix ER signal peptide

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127
Q

Lysosomes

Pathway and Signal

A

Secretory pathway

Mannose-6-phosphate signal group

And N-terminal hydrophobic alpha helix ER signal peptide

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128
Q

Secretion

Pathway and signal

A

Secretory pathway

Tryptophan-rich domain signal region, absence of retention motifs

And N-terminal hydrophobic alpha helix ER signal peptide

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129
Q

Membranes

A

Secretory pathway
N-terminal apolar region (stop-transfer sequence)

And N-terminal hydrophobic alpha helix ER signal peptide

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130
Q

Signal sequences for ER lumen proteins

A

KDEL

K- Lysine

D- Aspartic acid

E- Glutamic acid

L - Leucine

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131
Q

Secretory Pathway

A

Each protein has an ER-targeting signal peptide that has:

1-2 basic amino acids near N terminus

And an extremely hydrophobic sequence on C terminus of base residues

Translation occurs on the ER

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132
Q

Translation on the ER

A
  • Signal recognition particle (SRP) binds to the ER-targeting signal and the ribosome during translation, SRP wraps itself around ribosome-mRNA-peptide complex, halting translation which is resumed when the protein is directed into the ER lumen
    Enzymes on luminal side cleave signal to release protein, which undergoes PTM’s
    Additional signal sequences guide each protein to its final destination
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133
Q

Post-translational processing

A

Protein folding
Proteolytic cleavage
Covalent modifications

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134
Q

Protein folding

A

Small proteins can fold into native confirmations spontaneously , large proteins require chaperones and chaperonins ex HSP60 that utilizes ATP to fold proteins

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135
Q

Proteolytic cleavage

A
  • converts inactive forms to active enzymes

- converts nascent precursor proteins to mature ones

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136
Q

Covalent modifications

A
  • Glycosylation
  • phosphorylation
  • disulfide bond formation
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137
Q

Glycosylation

A

Extracellular proteins (glycoproteins) that are either O-glycosidic of N-glycosidic linked

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138
Q

O-glycosidic linkage

A

Formed with the hydroxyl groups of Ser or Thr residues

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139
Q

N-glycosidyl linkages

A

Always formed with asparagine, precursor sugar transferred from phospho Dolichol

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140
Q

Phosphorylation

A

Formation of an ester bond between phosphate and OH of an amino acid via activity of serine/threonine and tyrosine kinase

Phosphate removed by phosphatases

  • regulates enzyme activity, protein function, cell growth, proliferation, differentiation, oncogenesis
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141
Q

Disulfide bond formation

A

Inter and intra-molecular disulfide bonds stabilize proteins, forming between thiol (SH) and two cysteine resides

Formation and reorganization occurs in the ER lumen and is facilitated by protein disulfide isomerases

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142
Q

Processing of preproinsulin to mature insulin

A

Produced as preproinsulin in B cells of pancreas

Signal peptide cut off in ER lumen to form proinsulin

Folds to form 2 intramolecular disulfide bridges

Moves past golgi and accumulates in B granules

Cleaved twice to release the 33 reside C peptide

Forms mature insulin with A and B peptide joined by 2 disulfide linkages

Stored in granules as a Zinc bound hexamer that is ready to be secreted

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143
Q

Immunoawway for circulating C peptide

A

Used as a test for assessing function of beta cells

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144
Q

Posttranslational modification of collagen congenital disorders of glycosylation

A
  • Collagen is most abundant structure and hetermotrimeric
  • Lysines in procollagen hydroxylated to form 5’hydroxyl lysins that are further modified by glycosylation by addition of glucose and galactose
  • Prolines hydroxylated to from 4 and 3-hydroxyproline

These modifications are necessary for correct crosslinking and assembly

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145
Q

Diseases caused by mutations in lysyl hydroxylases

A

Ehlers Danlos syndrome

Nevo syndrome

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146
Q

Ascorbic acid

A

Essential for functioning of lysyl and prolyl hydroxylases

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147
Q

Locus

A

Specific place on a chromosome occupied by a gene

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148
Q

Centromere

A
  • temporarily holds 2 daughter DNA double helices together after DNA replication
  • attachment site for microtubules
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149
Q

Telomeres

A

Repeated nucleotide sequences at the end of a chromosome which are essential for chromosome stability

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150
Q

Karyotype

A

Entire set of stained chromosomes from a single cell

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151
Q

Autosomes

A

Chromosomes 1-22

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152
Q

Sex chromosomes

A

Pair 23, male and female

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153
Q

Chromatid

A

Identical sisters present after DNA replication

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154
Q

Metacentric

A

Centromere is positioned in the center

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155
Q

Telocentric

A

Centromere is located near the telomere

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156
Q

Karyotpying

A

Allows determination of number, size and gross structure of metaphase chromosome, used to identify several chromosomal abnormalities associated with genetic disorders, does not provide information at molecular level

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157
Q

Genotype

A

Individual’s genetic makeup

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158
Q

Phenotype

A

Physical manifestation of gentoype that is actually observed

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159
Q

Proband

A

First diagnosed person in pedigree

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160
Q

Autosomal dominant inheritance

A

Only 1 allele needed for expression

Affected offspring has one affected parent

Unaffected individuals do not transmit trait

Gender does not affect transmission

Trait is expected in every generation

Ie. Postaxial polydactyly

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161
Q

Vertical transmission

A

Trait is expected in every generation

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162
Q

Postaxial polydoctyly

A

Autosomal dominant inheritance, extra fingers

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163
Q

Autosomal recessive inheritance

A

2 copies of a gene is needed to influence phenotype

  • Tyrosine-negative albinism
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164
Q

Tyrosinase-negative albinisim

A

Autosomal recessive inheritance

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165
Q

X-linked recessive

A

Unaffected males do not transmit the trait (no carriers)

Female carriers transmit affected allele 50% of the time

All daughters of affected males are carriers

Ex. Duchenne muscular dystrophy

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166
Q

Duchenne muscular dystrophy

A

X-linked recessive

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167
Q

X-linked dominant

A

No carriers

Males transmit the trait to only females, 100% of whom are affected

Females transmit trait to 50% of offspring

ex. Hypophosphatemia

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168
Q

Hypophosphatemia

A

X-linked dominant

  • low levels of phosphorus in blood
  • abnormal metabolism of Vitamin D (can cause rickets)
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169
Q

Reduced penetrance

A

Frequency a gene manifests itself

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170
Q

Variable expressivity

A

Range of phenotypes that vary between individuals with a specific genotype

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171
Q

Locus heterogeneity

A

Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci

Ex. Ostogenesis imperfecta

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172
Q

Osteotenesis imperfecta

A

Locus Heterogeneity

  • brittle bone disease
  • mutations in collagen genes
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173
Q

Neurofibromatosis

A

Variable expressivity

Develop tumor-like growths called neurofibromas, and develop cafe-au-lat-spots

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174
Q

Retinoblastoma

A

Autosomal dominant inheritance

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175
Q

De novo mutation

A

Alteration in gene that is present for the first time in one family member as a result of a mutation in a germ cell of one of the parents or in the fertilized egg itself

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176
Q

Pleitropy

A

One gene influences two or more seemingly unrelated phenotypic traits

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177
Q

Interphase

A

Time for acquisition of nutrients growth, and chromosome duplication

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178
Q

Meiosis I

A

Separates the pairs of homologues with each daughter nucleus receiving one

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179
Q

Meiosis II

A

Separates the chromatids and parcels one chromatid into each of two more daughter nuclei, produces four haploid daughter nuclei

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180
Q

Prophase I

A

Homologous chromosomes pair up and exchange DNA, crossing over occurs

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181
Q

Chiasma

A

Exchanged sections of DNA produced during crossing over

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182
Q

Homologous recombination

A

Genes on one homologue are combined with an allele from the other homologue , an the combination may be totally new

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183
Q

Metaphase I

A

Paired homologous chromosomes line up at the equator of the cell, microtubules attach to kinetochore regions

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184
Q

Anaphase I

A

Homologous chromosomes separate

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185
Q

Telophase I

A

Two haploid clusters of duplicated chromosomes form at each pole

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186
Q

Meiosis II

A

Separates sister chromatids into four daughter nuclei

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187
Q

Mosaicism

A

Condition in which cells from an individual who has developed from a single fertilized egg have different genotypes

  • all females have roughly equivalent populations of two genetically different cell types and are therefore a type of mosaic
  • ex. Down syndrome (trisomy 21), Klinefelter syndrome, Turner syndrome
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188
Q

Lyonization

A

(X-inactivation) one of the copies of X chromosome present in female mammal is inactivated because it is silenced by heterochromatin

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189
Q

Genomic imprinting

A

Certain genes are expressed only from the mother or father, determined by methylation patterns on chromosomes

  • imprinted genes = methylation = down regulated
  • two chromosomes from same parent that have parent-specific imprinting = no gene product
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190
Q

Chromosomal mutations

A

Involve large segments of DNA, often encompassing millions of base pairs

4 types:

  • Inversion
  • Deletion
  • Duplication
  • Translocation
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191
Q

Inversion

A

A segment of chromosomal DNA is present in its reverse orientation

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192
Q

Deletion

A

Segment is lost

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193
Q

Nondisjunction

A

Homologs fail to separate properly

  • very common during egg development and increase with advancing maternal age
  • leading cause of spontaneous abortion and mental retardation in humans
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194
Q

Aneuploid

A

Cells with abnormal chromosome number

ie. Trisomy 21/ Down syndrome (90% of additional chromosomes in patients are maternal in origin)

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195
Q

Euploid

A

Cells with normal number of chromosomes

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196
Q

Prader Willi syndrome

A

Deletion on paternal chromosome 15

  • uncontrolled eating and obesity
  • uniparental disomy
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197
Q

Angelman syndrome

A

Deletion on maternal chromosome 15

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198
Q

Uniparental disomy

A

Occurs when a person receives 2 copies of a chromosome from one parent and no copy from another parent

  • often asymptomatic, but can cause delayed development, mental retardation

Ex. Prader Willi syndrome

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199
Q

Klinefelter syndrome

A

Mosaicism

Some cells are normal 46XY

Other cells are an extra X chromosome
47XXY

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200
Q

Trisomy 21

A

Down Syndrome

  • mental retardation
  • abundant neck skin
  • Flat facial profile
  • congenital heart defect
  • umbilical hernia
  • hypotonia
  • gap between first and second toe
  • intestinal stenosis
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201
Q

Trisomy 18

A

Edwards Syndrome

  • Prominent occiput
  • mental retardation
  • Low set ears
  • short neck
  • overlapping fingers
  • congenital heart defect
  • renal malformations
  • limited hip abduction
  • rocker-bottom feet
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202
Q

Trisomy 13

A

Patau syndrome

  • Microcephaly
  • mental retardation
  • polydactylty
  • cleft lip and palate
  • cardiac defects
  • umbilical hernia
  • renal defects
  • rocker-bottom feet
  • microophthalmia
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203
Q

Hardy-Weinberg Principle

A

Punnet square

Frequency of aa should be q-squared

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204
Q

Consanguinity

A

Blood related couple (marriage of first cousins) indicated by double horizontal lines, more likely to produce offspring affected by rare autosomal diseases

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205
Q

Polygenic

A

Traits in which variation is thought to be caused by the combined effects of multiple genes

Follows a normal bell-shaped distribution in populations

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206
Q

Multifactorial

A

Environmental factors cause variation in the trait

Follows a bell shaped distribution in populations

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207
Q

Threshold of liability

A

For multifactorial disease, this must be crossed before the disease is expressed

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208
Q

Pyloric stenosis

A

Muscular hypertrophy between stomach and duodenum, leading to vomiting and obstruction

5x more common in males

children of women affected with pyloric stenosis are more likely to be born with the condition

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209
Q

Recurrence risks

A

Affected by gene frequencies and environmental factors that differ among populations

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210
Q

RR:

More than one family member is affected

A

Recurrence risk is higher

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211
Q

RR:

Expression of the disease in the proband is more severe

A

Recurrence risk is higher

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212
Q

RR:

Proband is of the less commonly affected sex

A

Recurrence risk is higher

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213
Q

RR:

Remotely related relatives

A

Recurrence risk for the disease usually decreases rapidly

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214
Q

Multifactorial disease

A

Caused by the simultaneous influence of multiple genetic and environmental factors

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215
Q

Genetic drift

A

Random evolutionary process that produces larger changes in gene frequencies in smaller populations

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216
Q

Founder effect

A

Population that have started from a small group that mix with few newcomers, preferring to mate within the population

  • genetic drift
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217
Q

Growing phase/interphase

A

G1, S, and G2

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218
Q

G1

A

Gap 1

RNA and protein synthesis occur in response to exogenous growth factors (mitogens) to create the proteins that are needed to replicate DNA in the next phase

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219
Q

S

A

Synthesis

DNA is replicated, and RNA and proteins are synthesized

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220
Q

G2

A

Gap 2

RNA and protein synthesis continues and the integrity (correctness, stability) of the DNA is checked as the cell prepares to split/divide into two

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221
Q

M

A

Mitosis

Nuclear and cytoplasmic division occurs to create two identical daughter cells, phase is further divided into prophase, metaphase, anaphase, telophase, and cytokinesis

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222
Q

G0

A

Resting stage

Cells have excited the cell cycle and are not growing or dividing, however they synthesize just enough RNA and protein for general housekeeping of for specialized functions

  • quiescent state
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223
Q

Cell types

A
  1. permanent
  2. Stable (quiescent)
  3. Labile
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224
Q

Permanent cells

A

Remain in the G0 phase and cannot be regenerated

Ie. Cardiac muscle cells, neurons, and red blood cells

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225
Q

Stable cells

A

Retain the ability to exit G0 and enter G1 when stimulated by growth factors, allowing regeneration of damaged tissues

Ie. Hepatocytes, epithelial cells of kidney tubules

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226
Q

Labile cells

A

Never enter G0 and are constantly dividing to replace cell populations that are continuously lost

Ie. Gut epithelium, skin, hair follicles, and bone marrow

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227
Q

Restriction point

A

When growth factors are limiting, cell cycle is usually arrested in G1 at a point approximately 2 hours before the initiation of S phase

Everything downstream is growth factor independent

  • when cells pass the restriction point, they become growth factor independent and transit through the remaining phases
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228
Q

G1 checkpoint

A

Correct any DNA damage (chemical modification) before continuing

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229
Q

G2 checkpoint

A

Verify completeness of complete genomic duplication

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230
Q

Metaphase checkpoint

A

Ensures chromosomes are attached to mitotic spindle

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231
Q

DNA content

A 
G1: 2N
S: Between 2N and 4N
G2: 4 N
M: 4N
Cytokinesis: 2N
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232
Q

Chromosomes

A

Somatic cells which are diploid contain 46 chromosomes

Germline cells which are haploid contain 23 unpaired chromosomes

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233
Q

Cyclin

A

Regulatory subunit

Proteins that regulate Cdks

Without cyclin, Cdk is inactive

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234
Q

Cyclin-dependent kinase (CDK)

A

Catalytic subunit

Inactive without Cdk

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235
Q

G1 cyclin (D)

A

Helps the passage of cells through the restriction of point in late G1 phase

  • Cyclin D-CDK4
  • Cyclin D- CDK6
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236
Q

G1/S cyclin (E)

A

Helps the cells at the end of G1 phase to commit to DNA replication and enter S phase

  • Cyclin E- CDK2
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237
Q

S phase cyclin (A)

A

Necessary for the initiation of DNA synthesis

  • Cyclin A-CDK2
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238
Q

M Phase cyclins (A and B)

A

Necessary for the nuclear division during mitosis

CyclinA - CDK1
CyclinB- CKD1

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239
Q

Cyclin-CDK complex

A
  • heart of the cell-cycle control system
  • activities of Cdks rise and fall during cell cycle
  • causes changes in phosphorylation of substrates that regulate cell cycle events
  • Cyclins: proteins that regulate Cdks
  • without cyclin, CDK inactive
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240
Q

CDK-activating kinase (CAK)

A

Required for the full activation of Cyclin-CDK complex

Phosphorylates cdk

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241
Q

CDK inhibitors (CKIs)

A

Ie. p27 of the CIP/KIP family binds to the cyclin-CDK complex to inactivate the kinase activity of CDK

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242
Q

T loop

A

Protein that blocks active site of Cdk and is removed by binding to cyclin, phosphorylation

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243
Q

CIP/KIP family

A

CKIs bind to G1 and S phase cyclin, CDK complexes to inactivate the kinase activity of CDK

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244
Q

INK4

A

Family of CKIs that bind specifically to G1 CDKS to prevent them from associating with cyclin D

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245
Q

WEE1 kinase

A

Enzyme that Phosphorylates CDK to inhibit cyclin-CDK activity

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246
Q

Myc

A

Gene regulatory protein

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247
Q

Retinoblastoma protein

A

Tumor-supressor protein that can arrest the cell cycle at the G1 checkpoint, substrate of G1 and G1/S cyclin CDK complexes

  • hypophosphorylated form binds to E2F transcription factor to prevent transcription of cyclin E and cyclin A and proteins involved in DNA replication
  • Hyperphosphorylation by cyclin-CDK complexes releases the E2 factors to allow transition of cells past G1 checkpoint
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248
Q

P53

A

Activation of p53 by DNA damage (caused by chemical or physical agens) activates protein kinases and leads to increased transcription of p21, a CKI which causes cell cycle arrest

MDM2 keeps p53 inactive

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249
Q

Proteolysis of cyclins

A

A mechanism used to terminate the activity of cyclin-CDK complexes via degradation of the transiently expressed cyclin proteins. Cyclins are targeted by polyubiquitination catalyzed by ubiquitin ligases.

Ubiquitin ligases can also target CKIs, thus releasing the inhibition of S phase cyclin-CDK complexes

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250
Q

Retinoblastoma and the RB protein

A

Tumors develop due to unchecked division of precursor cells in the immature retina,

hereditary: affects both eyes, RB gene is mutated or lost in every cell, if both copies are damaged the cells lose control at the G1 checkpoint
Nonhereditary: affects one eye, cells contain different somatic mutations of the two copies of the RB gene

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251
Q

CDC25

A

Phosphatase that can remove the phosphate group introduced by WEE1 to reactive the cyclin-CDK complex

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252
Q

P53 and cancer

A

metabolic Activated benzopyrene and Aflatoxin (carcinogens) cause mutations in genes such as p53 by G->T transversions

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253
Q

Replicative cell senescence

A

Human skin fibroblasts stop dividing after 30 to 50 population doublings even with abundant growth factors present due to shortening of telomeres with each cell division

DNA damage leads to p53 mediated cell arrest at the G1 checkpoint

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254
Q

Apoptosis

A

Extrinsic Pathway

Intrinsic Pathway

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255
Q

APC complex (Anaphase-promoting complex or cyclosome)

A

Member of ubiquitin ligase family of enzymes

** Degradation and cell turnover

Targets S-cyclins and M-cyclins, adding polyubiquitin to M-cyclin in M-Cdk complex

Activated by binding to Cdc20

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256
Q

Extrinsic

A

Death receptor pathway, triggered by external binding and activation of an external death ligand to it receptor on the plasma membrane

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257
Q

Fas signaling (FADD)

A

Fas binds to Fas death receptor - ligand form homotrimers as well

  • adapter proteins are recruited: FADD adapter & procaspase-8 with death effector domain

Activates downstream executioner caspases (caspase-3)

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258
Q

Caspase activation

A

Caspase 8 must be formed to carry out apoptosis by activating caspase 3,6,7

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259
Q

Initiator caspases

A

Initiate apoptosis

  • Caspase 8
  • Caspase 0
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260
Q

Executioner caspases

A

destroy actual targets

Executes apoptosis and includes caspase 3

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261
Q

RB protein is a major regulator of

A

Cell cycle/apoptosis

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262
Q

Intrinsic pathway

A

Mitochondrial dependent
- in response to injury, DNA damage, and lack of oxygen, nutrients, or extracellular survival signals

  • BAX/BCL regulators

Cytochrome C is released from mitochondria, binds to Apaf1

Apaf1 forms apoptosome which activates caspase-9

Caspase-9 activates caspase-3 (executioner)

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263
Q

Apaf1

A

Forms apoptosome

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264
Q

BAX (BH123)

A

Protein that becomes activate, forms aggregation in mitochondrial outer membrane and induces release of cytochrome C

  • the apoptosome is then formed by binding to Apaf1
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265
Q

BCL-2

A

Located on cytosolic surface of out mitochondrial membrane

  • prevent apoptosis by binding to pro-apoptotic proteins (BAX/BH123) and preventing aggregation into active form
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266
Q

Cytochrome C

A

Released from mitochondria, binds to procaspase activating adaptor protein (Apaf1) which actives caspase-9, which activates caspase-3

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267
Q

Induction

A

A group of cells/tissues change their fates in response to signals

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268
Q

Competence

A

Capacity to respond to inductive signal

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269
Q

Transcription Factors

A
  • proteins with domains that bind to promoter or enhancer regions & domains that interact with RNA polymerase II
  • regulate amount of mRNA that gene produces
  • Homeobox - homeodomain containing genes/ Hox genes
  • T-box gene family
  • Helix-loop-helix (structure)
  • Zinc finger proteins (structure)
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270
Q

Homeobox

A

DNA sequence that encodes the homeodomain

  • involved in the regulation patterns of anatomical development (morphogenesis)
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271
Q

Hox genes

A

Homeo-box containing gene, classified by structure

Long, repetitive elements of promoter elements that regulate anatomical development and then turn off

Expressed and activated in the 3’ to 5’ direction

Majorly regulated by retinoic acid

TF

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272
Q

Homeodomain

A

60 amino acid helix-turn-helix DNA binding domain

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273
Q

Retinoic acid

A

Vitamin A

  • regulates Hox genes
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274
Q

Pax gene family

A

Play critical role in the formation of tissues and organs during embryonic development, maintains normal function in cells after birth

Plays role in development of nervous system and sense organs

Contain paired domain of 128 amino acids which bind to DNA

  • can turn on large amounts of proteins at one time

TF

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275
Q

Lim proteins

A

Involved in formation of virtually all body segments

Large family of homeodomain proteins

Absence can result in headless embryos

TF

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276
Q

Dlx genes

A

Growing of appendages, jaw, and inner ear

Early embryogenesis

TF

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277
Q

Msx

A

Prenatal - inhibits cell differentiation

Postnatal - maintain proliferative capacity of tissues

Also involved in epithelial-mesenchymal interactions in face & limbs

TF

278
Q

T-box (Tbx) Gene family

A

Important in mesodermal germ layer development

Determines forelimb and hindlimb

TF

279
Q

Helix-loop-helix

A

Transcription factors that are named on appearance

Regulate myogenesis

280
Q

Forkhead (fox) gene family

A

Regulates expression in genes involved in cell growth, proliferation, differentiation, and longevity

  • positive selection associated with human specific phenotype

TF

281
Q

Zinc finger proteins (Sox genes)

A

Bind to minor groove in DNA & belong to a super-family of genes characterized by a homologous sequence called the HMG-box

Regulate myogenesis

  • SoxA = SRY, sex determining region of Y chromosome

TF

282
Q

SoxA

A

SRY, sex determining region of Y chromosome

283
Q

Hedgehog proteins

A

Set of proteins that binds to ligand receptor complex and acts as a signal

Binds to PTCH on surface of target cell, which is bound to SMO, a transmembrane protein

*NOT a transcription factor

284
Q

Wnt Family

A

Proteins that bind to cell surface receptors

Signal

Ligands

NOT TF

285
Q

Proto-oncogene

A
  • RAS
  • HER2
  • EGF receptor
  • N-MYC
  • c-MYC
  • ABL

Working normally is fine, when mutated causes problems

286
Q

RAS

A

Proto-oncogene

Point mutation/deletion

  • point mutation changes glycine to valine at codon 12
287
Q

Proto-oncogene point mutations/deletions

A
  • RAS
  • HER2
  • EGF receptor
288
Q

Proto-oncogene gene amplification

A
  • HER2

- N-MYC

289
Q

Proto-oncogene

Chromosomal translation

A

c-MYC

ABL

290
Q

PCR

A

Polymerase chain reaction (cell-free cloning)

Used for diagnosing infections and genetic testing

291
Q

Antibodies

A

B-cells are converted to secrete them

292
Q

Fab domain

A

Antigen binding domain formed by heavy and light chains coming together

293
Q

Epitope

A

Specific site of the antigenic molecule the Fab region recognizes

294
Q

Indirect ELISA

A

Production of color indicates the amount of an antibody to a specific antigen

295
Q

sandwich ELISA

A

Production of color indicates the quantity of antigen

296
Q

PCR

A

Can be used to detect altered genes or foreign DNA

297
Q

Primers

A

Starting points for transcription

  • small (~20 nucleotides_
  • complimentary to some portion of singe stranded DNA
298
Q

Solid phase enzyme linked immunosorbet assasy

A

ELISA

Measures the levels of specific antigen or antibody concentrations in biological samples using a corresponding immobilized antibody or antigen

299
Q

Acute phase of Zika

A

1st week,

300
Q

Zika subacute/chronic phase

A

2-12 weeks

  • Use ELISA AND confirmatory PRNT
301
Q

1st week of Zika

A

PCR

302
Q

2-12 weeks of Zika

A

ELISA + confirmatory PRNT

303
Q

Growth and differentiation factors

A

FGF (fibroblast growth factor)
Hedgehog proteins
Transforming growth factor B (TGF-B) Superfamily
WNT proteins

304
Q

TGF-B Superfamily

A

Transforming growth factor

Involved in embryogenesis and postnatal life

305
Q

Fibroblast Growth Factors (FGFs)

A

Variation

Broad spectrum of roles, closely associated with the ECM

306
Q

P53

A

Monitors checkpoints of cell cycle

  • tumors
307
Q

RB

A

Regulates G1 phase of cell cycle

Observed in retinoblastoma

308
Q

APC

A

Regulates cell proliferation

Colon cancer

309
Q

DCC

A

Cell proliferation, migration, and apoptosis

Colon cancer

310
Q

BRCA1/BRCA2

A

DNA repair and apoptosis

Breast cancer

311
Q

NF-1

A

Encodes GTPase-activating protein (GAP) which normally turns off activated RAS protein

Neurofibromatosis

312
Q

Myc

A

Transcription factor regulating Cdc25 protein tyrosine phosphatase

(Growth regulation hormone)

313
Q

Cdc2

A

Regulation of S/M phase transition

Growth regulation gene

314
Q

BCL-2 family

A

Cell survival

315
Q

Fast response

A

Change in activity or function of enzymes or proteins in a cell

316
Q

Slow response

A

Change in amounts of proteins by change in expression of genes

317
Q

Leptin

A

Released from fat

Signals hypothalamus that you are full

318
Q

Endocrine signaling

A
  • long distance

Signal ->bloodstream-> distant target cells

  • freely diffusible signals
  • stable

(Hormones)

319
Q

Paracrine signaling

A

Acts locally

  • affects cells nearby (not as freely diffusible)
  • short lived signal
  • ie. Neurotransmitters
320
Q

Autocrine singaling

A
  • Cells respond to signals that they themselves release or release to cells of the same type
  • cells secretes signal that feeds back and binds to a receptor on its own surface
  • ie. Growth factors and cancer cells
321
Q

Direct cell signaling/ Juxtracrine signaling

A

Ie. Immune cells, Ag-presenting cells to T cells

322
Q

Acetylcholine

A

Heart muscle cells : relax
Skeletal muscle cells: contract
Salivary gland cell: secretion of saliva

323
Q

Cell signaling

A

Cascade of events involving

  1. signals (ligands)
  2. Receptors
  3. Effectors
324
Q

Signals (ligands)

A
  • typically secreted by exocytosis
  • signals stay near or far

Are either lipophilic or hydrophilic

325
Q

Receptors

A

Bind specifically to signal molecules with high affinity (signals are produced in low levels)

  • intracellular
  • cell surface receptor
326
Q

Effectors

A

Targets of receptors inside cells: alter activity of many different proteins and generate 2nd messengers like cAMP and Ca2+

327
Q

Lypophilic signaling molecules

A

Lipid-loving

Steroid hormones
Thyroid hormones
Retinoids: Retinoic acid

  • found in the cytoplasm and nucleus
  • family of DNA-binding transcription factors
328
Q

Hydrophilic signaling molecules

A

Water-loving, growth factors

Amino acid derived
From lipid metabolism
Polypeptides

  • found on the surface of plasma membranes
  • includes transmembrane proteins such as G protein-coupled receptors and receptor tyrosine kinases
329
Q

Intracellular receptors

A

Steroid receptor in cytosol that can alter gene expression in the nucleus

330
Q

Cell surface receptors

A

External domain binds ligand, transmembrane domain anchors receptor, cytoplasmic domain initiates signal by change in conformation

331
Q

Hydrophilic signaling molecules

A

Require cell-surface receptors

332
Q

Small hydrophobic signaling molecules

A

Can diffuse across the cytoplasmic membrane and bind to intracellular receptors

333
Q

Cell signaling receptors in the plasma membrane

A
  1. Gated ion channels common in nervous tissue
  2. GPCRs use 7-pass transmembrane proteins
  3. Enzyme-coupled receptor class including receptor tyrosine kinases (RTKs)
334
Q

G-protein coupled receptors

A

Composed of:

  • Extracellular domain
  • transmembrane domain
  • cytoplasmic domain

GCPR -> Trimeric G protein -> effector enzyme -> 2nd messenger -> Targets of 2nd messenger -> biological response

335
Q

Extracellular domain

A

Binds to ligand

336
Q

Transmembrane domain

A

Anchors receptor

337
Q

Cytoplasmic domain

A

Associates with G-proteins

338
Q

Heterotrimeric G-proteins

A

Guanine nucleotide-binding proteins that consist of 3 subunits designated alpha, beta, and gamma

Changes conformation if bound by a ligand

339
Q

G-proteins do not transfer

A

Phosphates

340
Q

GEF

A

Guanine nucleotide exchange factor

Phosphorylates GDP to GTP

341
Q

GAP

A

GTPase activating protein

Increases the intrinsic GTPase activity

342
Q

Steps of G-protein relaying signals

A
  1. Ligand binds to receptor
  2. Conformational change occurs in receptors
  3. Receptor binds to G protein
  4. Receptor then acts as a GEF
  5. Confirmation of a G alpha protein is changed to kick out GDP and GTP binds to it
  6. G alpha now becomes active and can bind to effector molecule and activate effector molecule
  7. Effector molecule in this case is adenylyl cyclase which catalyzes formation of cAMP
343
Q

Adenylyl cyclase

A

Catalyzes the formation of cAMP

344
Q

Camp

A

Activates cAMP-dependent protein kinase (PKA) -4 subunits

345
Q

Inactive PKA

A

2 catalytic subunits & 2 regulatory subunits

346
Q

Active PKA

A

2 cAMP molecules bind to regulatory subunits of the PKA tetramer, releasing the active C subunits

Active PKA can now phosphorylate other proteins

347
Q

Retinoic Acid

A

Derived from Vitamin A

Excess results in broad spectrum of abnormalities

*Acts through Hox genes

348
Q

PLC

A

Catalyzes formation of DAG and IP3

349
Q

GTP bound form

A

Active form

350
Q

Cholera Toxin

A

Modifies G protein by keeping the G alpha in the GTP active form indefinitely

This causes increase in cAMP

PKA phosphorylates the CFTR cl- channel

This leads to secretion of water

351
Q

Potentiate

A

Turn up

352
Q

Attenuate

A

Turn down

353
Q

Desensitization

A

Ability to turn off or reject the signal

  • hormone levels drop (decreased AC, decreased cAMP
354
Q

Phosphodiesterase

A

Removes signaling molecule (cAMP or cGMP)

E.g. Viagra, keeps vasodilation high

355
Q

GRKs

A

G protein receptor kinases, phosphorylate the receptor

356
Q

Arrestin

A

Will bind to the 3rd intracellular loop and prevents Ga from interacting with the third loop

  • requires GRK to phosphorylate the receptor first
357
Q

PLC makes

A

IP3 and DAG by cleaving PIP2

358
Q

RTKs

A

Receptor tyrosine kinases

Ligand binds and causes conformational change that opens up “docking sites” for phosphorylation

Mediate growth factor signals

359
Q

Growth factors

A

Proteins released by cells to promote growth of other cells

360
Q

SH2 domains

A

Bind to phosphotyrosine

T: Tyrosine and Two

361
Q

Grb2

A

Has SH2 and SH3 domains in SOS (REF)

362
Q

SH3

A

Binds to prolines

363
Q

Ras

A

Monomeric G protein, binds Raf

364
Q

SOS

A

Son of sevenless, ras GEF

365
Q

Erk

A

MAP kinase,

366
Q

Ras activates:

A

Raf (MAP kinase, kinase, kinase) -> Mek (MAP kinase, kinase) -> Erk (MAP kinase)

367
Q

JAK-STAT receptors

A

Kinases that phosphorylate each other

368
Q

R-Smad

A

TGF-beta activates TGF beta receptors, Smads get phosphorylated and go to the nucleus

369
Q

G Alpha i

A

Adenylyl cyclases

  • inhibition of cAMP production, ion channels, phosphodiesterases, phospholipase
370
Q

G alpha q

A

PLC-B
DAG
Ca2+
PKC

371
Q

G Alpha S

A

Adenylyl cyclases

Increase in cAMP concentration

372
Q

Epinephrine, B-adrenergic receptor, Gs

A
  • Relaxation of bronchial and intestinal smooth muscle
  • Contraction of heart muscle
  • Increased breakdown of triacylglycerols in adipose tissue
  • Increased breakdown of glycogen in liver and muscle
  • Increased Glycolysis in muscle
373
Q

Histamine, Histamine H2 receptor, Gs

A
  • Bronchoconstriction and sx of allergic reaction
374
Q

Epinephrine/Norepinephrine, a-adrenergic receptor, Gi

A
  • constriction of smooth muscle
375
Q

Dopamine, Dopamine D2 receptor, Gi

A
  • increased heart rate
376
Q

Acetylcholine, Muscarinic acetylcholine M3 receptor, Gq

A
  • Bronchoconstriction and stimulation of salivary glands
377
Q

Light, Rhodopsin, Gt

A

-Vision

378
Q

Monomeric receptors that become dimered upon activation

A
  • Tyrosine kinases
  • JAK-STAT receptors
  • Serine/Threonine kinases
  • all create docking sites for other proteins
379
Q

Connective tissue

A

Bone or tendon, lots of extracellular matrix with sparse cell distribution

380
Q

Epithelial tissue

A

Cytoskeleton of cells linked cell to cell by that are anchored to the basal lamina

381
Q

Anchoring junctions

A

Cell-cell adhesion and cell-matrix adhesion, and are connected to cytoskeletal filaments inside the cell

  • Actin filament attachment sites
  • Intermediate filament attachment sites
  • integrins
  • cadherins
382
Q

Occluding junctions

A

Seal gaps between epithelial cells so as to make the epithelial sheet into an impermeable barrier

383
Q

Channel-forming junctions

A

Create passageways for small molecules and ions to pass from cell to cell

384
Q

Signal-relaying junctions

A

Allow signals to be relayed from cell to cell across their plasma membranes at cell-to-cell contact

385
Q

Cadherin

A

Mediating cell-cell connection

Bind to partner with Low affinity

Mediate Ca2+ dependent

386
Q

Integrin

A

Mediating attachment of cells to matrix

Alpha and beta subunits

Always form a dimer

387
Q

Transmembrane adhesion proteins

A
  1. Cadherin
  2. Intergrins
  3. Selectins
  4. Immunoglobulin-superfamily
388
Q

Homophilic adhesion

A

Like cells bind to each other

389
Q

Heterophilic interactions

A

Different cells come together

390
Q

Classical adherins

A

Main mediatiors of CA2+ dependent adherens junctions

  • E-cadherin
391
Q

Nonclassical cadherins

A

Desmocollins and demogleins that form desosome junctions

392
Q

B-catenin

A

Link between cadherin and cytoskeleton

393
Q

Adherens junctions

A

Model the shape of the cystoskeleton

  • often form continuous adhesion belt and contractile bundle of actin filaments

** cadherin is crucial component

394
Q

Desmosome

A

Connects intermediate filaments in one cell to those in the next cell

395
Q

Desmosome proteins

A

Desmoglein and desmocollin

Mechanical strength

396
Q

ARVC

A

Common cause of sudden cardiac death in the young due to improper insertion of desmocollin into the membrane

397
Q

Tight junctions

A
  • form a seal between cells
  • form a fence between membrane domains
  • recruit cytoskeleton as well as signaling molecules
  • claudin
  • occludin
398
Q

Tight junction protein

A
  • claudin
  • occuldin
  • like claudins bind and like occludins bind
399
Q

Polarity complex

A

Par (partitioning defective), crumbs, and scribble

  • control polarization processes and maintain polarity
400
Q

Gap junction

A

spanned by channel-forming proteins

  • connexins

Couple cells both electrically and metabolically

*** SMALL molecules like ions, nothing bigger than a glucose can go through

401
Q

Large influx of Ca2+ into gap junction

A

Causes channels to close immediately, isolating cell damage and preventing spread to other cells

402
Q

Fibroblast

A

Cells that secrete matrix macromolecules

403
Q

Basal lamina

A

Separates cells and epithelia from underlying or surrounding connective tissue and forms the mechanical connection between them

Made up of :

  1. Fibrous protein (ususally glycoproteins)
  2. Glycosaminoglycan (GAG) polysaccharide chain
404
Q

Basal lamina in kidney glomerulus

A

Lies between two cell sheets and functions as a selective filter

405
Q

Lamina

A
  • laminin
  • collagen
  • fibronectin
406
Q

Actin to integrin

A

Provides components to crawl

  • this is mediated by talin
  • focal adhesion knase.
407
Q

Src/Focal adhesion kinase (FAK) complex

A

Central signaling molecule downstream from integrins which activates erk and JNK to regulate cell survival, proliferation, and differentiation

408
Q

Extrecellular macromolecules

A

Make up the matrix

  1. Glycosaminoglycans (GAGs)
  2. Fibrous proteins
409
Q

Glycosaminoglycans (GAGs)

A

Usually covalently linked to protein in the from of proteoglycans

  1. Chondroitin sulfate
  2. Dematin sulfate
  3. Heparan sulfate
  4. Keratan sulfate
  • strongly hydrophilic
  • form gels, providing mechanical support to tissue
410
Q

Fibrous proteins

A

Collagen and fibronectin, which have both structural and adhesive functions

411
Q

Proteglycans

A

Form highly hydrated, gel-like ground substance in which the fibrous proteins are embedded

  • bind to signal molecules and can enhance or inhibit their signaling activity
  • contain a special link tetrasaccharide attached to serine side chain on core protein

Consist of long polysaccharides (GAGs) connected to protein core

  • polar, very hydrated (squishy tissue)
412
Q

Chondroitin

A

Old people drink for bones

413
Q

Aggregates

A

Long polysaccharide/core complex linked to extensive hyaluronic acid chain

414
Q

Hyaluronan

A

Repeating disaccharide ( glucaronic acid and N-acetylglucosamine), contains a lot of water, extremely long chain component of proteoglycan

415
Q

Collagen Type IV

A

Network forming

416
Q

Collage Type I

A

Bone, most abundant

417
Q

Collagens

A

Long, stiff, left handed triple-stranded helical structure (3 helical alpha chain)

  • filament
  • protofilament
  • rich in proline (kinks) and glycine (small, allows rope to pack tightly)
418
Q

Enzymes that are effecting hydroxylation

A

(lysyl/prolyl hydroxylases)

Hydroxylation occurs in the ER

  • hydroxylation of proline is necessary for collagen production and connective tissue remodeling
419
Q

Fibroblast

A

Site of collagen etc. synthesis

420
Q

Prolyl/ Lysyl hydroxlyases

A

Scurvy: loss of cofactor (ascorbate)

Ehlers-Danlos VI: defective enzyme

421
Q

Scurvy

A

Loss of cofactor ascorbate

  • prolyl/lysyl hydroxylases
422
Q

Ehlers-Danlos VI

A

Defective enzyme of prolyl/lysyl hydroxylase

423
Q

Elastin

A

Cross links protein via lysyl oxidase, can stretch and relax due to hydrophobic units

Hydrophobic units line up and get rid of water

424
Q

Marfan’s syndrome

A

Mutation of fibrillin that goes into elastic fibers

425
Q

Hypodermis

A

Fatty subcutaneous layer

426
Q

Dermis

A

second layer, rich in collagen, provides toughness

427
Q

Epidermis

A
  • out covering of skin
  • water barrier
  • epithelial cells
  • continuously repaired and renewed
428
Q

Fibroblasts

A

Secrete ECM and provide mechanical support

429
Q

Keratin filaments

A

Attach to desmosomes

430
Q

Hair follicle

A

Grows upword from dermal papilla

Have stem cells present in a bulge to aid in reconstruction

431
Q

Olfactory sensory neurons

A

Nose: neural epithelium, renew approximately every 30 days

432
Q

GPCR acts for senses

A

-light, taste, olfaction

433
Q

Olfactory receptor

A

Can bind to a single class of odorant molecules

Activated olfactory receptor activates G-protein -> AC -> cAMP -> ion channels open -> influx of Na and Ca -> action potential

434
Q

Actin filaments

A

Determine the shape of the cells surface
Necessary for whole-cell locomotion, secretion, endocytosis

  • compact and globular (G-actin vs. F-actin)
435
Q

Microtubules

A

Determine positions of membrane-enclused organelles and direct the intracellular transport, centrioles & mitotic spindle, cilia & flagella

  • from tubulin, have polarity
436
Q

Intermediate filaments

A

Mechanical strength, strong filament, resist mechanical stress

437
Q

ARP

A

Nucleation of actin filaments occurs near plasma membrane, so actin filaments mostly accumulate at cell periphery

Actin filaments determine the shape and movement of the cell surface

Nucleation of actin filaments by ARP complex creates polarity

438
Q

Y-TuRCs

A

Responsible for nucleation of microtubule growth

439
Q

Keratin

A

Most diverse group of intermediate filaments, anchor at sites of cell-cell contacts, desmosomes. Cell-matrix contacts (hemodesmosomes)

440
Q

Hematopiesis

A

Formation of blood units, occurs in:

Yolk sac : weeks 3-8 (splanchnic mesoderm)

Liver: week 6-30 (2nd trimester)

Spleen: Weeks 9-28 (2nd trimester)

Bone marrow: 28 weeks - adult

Adult: lymph, bones of axial skeleton (skull, vertebrae, ribs, sternum, clavicle, pelvis, long bones)

441
Q

Bone marrow

A

Red and yellow

Compartments: Hematopoietic cell compartment
Marrow stromal compartment

442
Q

Hemoatopoietic cell compartment

A

Highly vascular

Stem cells

443
Q

Erythroblastic area

A

Red cells

444
Q

Myeloid area

A

White cells

445
Q

Marrow stromal compartment

A

Production of growth factors
Barrier: separates hematopoietic compartment from central longitudinal vein

Removal of dead cells and debris (macrophage)

Energy source: adipose tissue

446
Q

Macrophage

A

Erythroblast compartment, removes dead cells and debris

447
Q

Barrier

A

Endothelial cells, separate blood cells from vein

448
Q

Newborn bone marrow

A

All starts off as red

449
Q

Yellow marrow

A

Based on the presence of apidocytes (fat cells)

450
Q

Normal marrow

A

In balance between red and yellow

451
Q

Stroma

A

Reticular connective tissue

Adipocytes and macrophages

452
Q

Sinusoids

A

Between cords

Allow cells into circulatory system

453
Q

Hematopoietic stem cell

A

Capable of self-renewal

Pleuripotent

454
Q

BFU

A

Red blood cells

455
Q

CFU-mega

A

Platelets

456
Q

CFU-GM

A

Monocyte and neutrophil

457
Q

Lymphoid

A

B lymphocyte, T lymphocyte

458
Q

Myeloid

A

BFU, CFU-mega, CFU-GM, eosinophil, basophil

459
Q

Hemoatopoietic Growth factors

A

Colony-stimulating factors
Erythropoietin, thrombopoietin
Cytokines

460
Q

Stem Cell Factor

A

Produced by fetal tissues and bone marrow
Weak stimulator of hematopoiesis
Makes stem cells responsive to other cytokines

461
Q

Flt3 ligand

A

Acts on pluripotent stem cells

462
Q

IL-3

A

Influenced replication and growth potential of hematopoietic progenitors

463
Q

IL 1 and 4

A

Acts on pluripotent stem cells to develop the lymphoid stem cells

464
Q

IL-2

A

T-cell growth factor

465
Q

IL 2 and 6

A

B-cell growth factor

466
Q

GM-CSF

A

Stimulates formation of all leukocytes

Less potent than G-CSF for increasing neutrophils

467
Q

G-CSF

A

Stimulates increase in neutrophils

468
Q

M-CSF

A

Stimulates increase in monocytes and macrophages

469
Q

EPO

A

Stimulate RBC formation

Produced in kidney

470
Q

TPO

A

Produced in the liver

Stimulated increase in megakaryocytes and platelets

471
Q

RBCs (erythrocytes

A

Deliver Ox from lungs to tissues

Picks up CO2 from tissues and unloads it on the lungs

472
Q

Thrombocytes (platelets)

A

Secrete vasoconstrictors

Stick together to form temporary platelet plug

473
Q

Proerythroblast

A

Large central nucleus
Ribosomes make hemoglobine
Mitotic

474
Q

Basophilic erythroblast

A

Smaller nucleus
Patchy chromatin
Basophilic cytoplasm
Mitotic

475
Q

Polychromatophilic Erythroblast

A 
Smaller nucleus
Condensed chromatin
Light blue staining clumps of polyribosomes
Light pink staining hemoglobin
Mitotic
476
Q

Orthochromatic erythrobloast

A

Dense, eccentric nucleus
Pink cytoplasm
No mitosis

477
Q

Reticulocyte

A

1% of circulating RBCs

No nucleus

478
Q

RBC

A

Mature cell, no nucleus

479
Q

EPO

A

Produced in kidney in response to hypoxia

480
Q

Thrombocytes

A

Megakaryoblast -> megakaryocyte -> platelets

481
Q

Megakaryoblast

A

Large oval nucleus
Basophilic cystoplasm

Becomes megakaryocyte

482
Q

Megakaryocyte

A

Mutilobed nucleus
Endomitos

Forms platelets

483
Q

Endomitosis

A

Nuclear division occur without cell division

484
Q

TPO

A

Regulates megakaryocyte and platelet development

Produced in live, kidney, and bone marrow

485
Q

Agranulopoiesis

A
  • heteromchromatin content increases
  • no specific granules from
  • no nuclear lobulation
  • cell sizes decreases
  • lymphocytes and monocutes
486
Q

Granulopoiesis

A
  • chromatin condenses
  • cytoplasmic granules
  • nucleus become lobulated
  • cell size decreases

** neutrophils, basophils, eosinophils

487
Q

Neutrophils

A

Phagocytize bacteria

Release antimicrobial chemicals

488
Q

Eosinophils

A

Phagocytize antigen-antibody complexes, allergens, and inflammatory chemicals

Antiparasitic and bactericidal activity

489
Q

Basophils

A

Secrete histamine and heparin

Inflammatory reactions during immune responses and allergies

490
Q

Granulocytes

A

Myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band -> polymorphonuclear neutrophil

491
Q

Myeloblast

A

No cystoplasmic granules
Mitotic
large round euchromatic nucleus

492
Q

Promyelocyte

A

Large flattened nucleus
More condensed chromatin
Azurophilic granules present
Mitotic

493
Q

Myelocyte

A

Indented nucleus
Specific granules accumulate
Smaller than promyelocyte
Mitotic

494
Q

Metamyelocyte

A

Meta “beyond”
Deeply indented nucleus
Densely packed specific granules
NO mitosis

495
Q

Band

A

Horseshoe shape nucleus
Chromatin condensed and lobulated
Higher numbers indicate infection

496
Q

Polymorphonuclear neutrophil

A

Mature cell

497
Q

Agranulocytes

A

Monoblast -> Promonocyte -> Monocyte -> macrophage

498
Q

Monoblast

A

Large round euchromatic nucleus
No cytoplasmic granules
Mitotic
Indentical to myeloblast

499
Q

Promonocyte

A

Large slightly intended nucleus

Divide several times before becoming monocytes

500
Q

Monocyte

A

Mature cell

501
Q

Macrophage

A

Emigrated blood monocytes that differentiate in tissues

Found at sites of infection

502
Q

Lymphocytesa

A

T and B cells

503
Q

B cells

A

Secrete antibodies

Mature in bone marrow

504
Q

T cells

A

Destroy cancer cells, virus infected cells, foreign cells

Mature in thymus

505
Q

Lymphoblast

A

Nucleus
1-2 nucleoli
No cytoplasmic granules

506
Q

Stem cell

A

Primitive cell that can either self-renew or give rise to more specialized cell types

507
Q

Totipotency

A

Ability of cell to give rise to all cells of an organism

*** Zygote

508
Q

Pluripotency

A

Ability of a cell to give rise to all cells of the embryo and subsequently adult tissues

*** embryonic stem cells

509
Q

Multipotency

A

Ability of a cell to give rise to different cell types of a given lineage

*** adult stem cells

510
Q

Founder stem cells

A

Can divide as stem cells giving rise to one daughter cell that remains a stem cell and a set of cells that have a set number of transit amplifying division

  • define size of large final structures
  • controlled by short range signals
  • each organ/tissue has fixed number of founder cells
511
Q

Transit amplifying cells

A

Divide frequently

Programmed to divide for a limited number of times

Part of strategy for growth control

Derived from founder cells

Daughter cell

512
Q

Divisional asymmetry

A

Creates 2 cells, one with stem cell characteristics and another with factors that give it the ability to differentiate

513
Q

Environmental asymmetry

A

Creates 2 identical cells but environment may influence/alter 1 cell

514
Q

Daughter cell

A

Gets new synthesized strand

Original DNA strand is preserved in stem cell

515
Q

Embryonic stem cells

A

From blastocyst stage of embryo

Can proliferate indefinitely in culture with unrestricted developmental potential

Develops into different cell types with characteristics appropriate for that site

516
Q

Spontaneous Embryonic stem cell differentiation in Vitro

A

Mixture of differentiated cells

517
Q

Gene regulatory proteins

A

Oct 3/4
Sox2
Myc
Klf4

518
Q

Hematopoeitic stem cells

A

Found in cord blood, bone marrow, and peripheral blood

519
Q

Mesenchymal stem cells

A

Found in wharton’s jelly, bone marrow, adipose tissue, and tooth pulp

520
Q

Adult stem cells

A

Have memory of developmental history and seems committed to its fate, which limits its clinical use

521
Q

Connexons

A

Make up connexins of gap junction

522
Q

Integrin molecule

A

Consists of 2 noncovalently associated subunits

Alpha and beta

Beta: binds to complex of proteins that form a linkage to the cytoskeleton
Alpha: active integrin

523
Q

Fibrillin

A

Glycoprotein

Mutation can cause Marfan’s syndrome

524
Q

Basal cell layer

A

Attach to basal lamina

Only dividing cells in epidermis

525
Q

Prickle cells

A

Attach to basal cell layer

Contain desmosomes that attach tufts of keratin filaments

526
Q

Granular cells

A

Attach to prickle cells

  • seal together to form waterproof barrier
  • form boundary between inner metabolically active strata and outer dead epidermis cells
527
Q

Squame

A

Outermost layer

  • flattened dead cells, densely pack with keratin but no organelles
528
Q

Overactivation of hedgehog pathway

A

Cells continue to divide even after exit from basal layer

529
Q

Deficit of hedgehog signal

A

Loss of sebaceous glands

530
Q

Up-regulation of Wnt signal

A

Extra hair follicles develop, giving rise to tumors

531
Q

Loss of Wnt signaling

A

Leads to failure of hair follicle development

532
Q

Notch signaling restricts

A

Size of stem cell population

533
Q

TGF beta

A

Plays key role in repair of skin wounds promoting formation of collagen rich scar tissue

534
Q

Centrioles

A

Organize the centrosome matrix, ensuring its duplication during each cell cycle

Attach to mitotic spindles

Arranged at a right angle to each other

535
Q

Rac activation

A

Promotes actin polymerization at the cell periphery -> formation of lamellipodia extensions

536
Q

Lamellipodia extensions

A

Caused by Rac activation

537
Q

Cdc42 activation

A

Triggers actin polymerization and bundling to from filopodia

538
Q

Filopodia

A

Triggered by cdc42 activation

539
Q

Rho activation

A

Promotes the bundling of actin filaments into stress fibers

540
Q

Hematopoietic Growth Factors

A
  • CSF: G-CSF, GM-CSG, M-CSF
  • Erythropoietin & Thrombopoietin
  • Interleukines: IL-3, IL-2, IL-6
541
Q

Somatic cell nuclear transfer (SCNT)

+/-

A

Immune rejection is not an issue because the patients are using their own cells

*early stem cell

542
Q

4 gene regulatory proteins

A

Oct3/4, Sox2, Myc, Klf4

543
Q

Nanog, Oct4, Sox2, FoxD3

A

These transcription factors are essential for establishment and maintenance of pluripotent stem cells in the embryo

544
Q

NANOG

A

Homeodomain

545
Q

Sox2

A

Zinc finger protein

546
Q

Oct4

A

Homeodomain

547
Q

Fox M1

A

Cell proliferation (acts directly on cyclin expression) Proto-oncogenes

548
Q

Myc

A

Helix-loop-helix transcription factors

549
Q

WT1

A

Zinc finger protein

550
Q

Klf1

A

Works with B-catenin (downstream of Wnt signaling)

551
Q

Pax, LIm, Msx, Dsx

A

Homeodomain

  • control differentiation during development of head and limbs
552
Q

TGF, FGF, Wnt, SHH

A

Growth factors that bind membrane receptors

  • control transcription factor activation of differentiation genes
553
Q

Blood composition

A

Cells and plasma (fluid component) can be separated by centrifugation

554
Q

Hematocrit

A

Percentage of erythrocyte volume: RBC’s constitute about 45% of blood volume

555
Q

RBC structure

A
  • non-nucleated
  • biconcave
  • no organelles
  • consist of plasma membrane, cytoskeleton, hemoglobin, and glycolytic enzymes
556
Q

Spectrin membrane skeleton

A

RBC’s rely on spectrin for flexibility to fit through capillaries and to maintain a certain shape to house glycolytic enzymes and hemoglobin

557
Q

Epliptocytosis

A

Alteration of RBC shape due to cytoskeleton defect (defective self association of spectrin subunits, defective binding of spectrin to ankyrin, protein 4.1 defects, abnormal glycophorin)

  • oval shaped RBCs
  • autosomal dominant
558
Q

Spherocytosis

A

Alteration in shape of RBC due to cytoskeleton defect (deficiency in spectrin)

  • anemia, jaundice, splenomegaly
  • autosomal dominant
559
Q

Sickle cell anemia

A

Hemoglobin abnormality caused by point mutation where glutamic acid is replaced by valine on hemoglobin chain, hemoglobin aggregates and is ineffective at binding oxygen

  • cells are sickle shaped
  • chronic hemolytic anemia, obstruction of post-capillary venules
560
Q

Thalassemia

A

Hemoglobin abnormality caused by defective synthesis of alpha or beta chains of hemoglobin tetramer

  • anemia
561
Q

Erythroblastosis fetalis

A

Hemolytic disease of the newborn: mother is Rh- and child is Rh+, creating antibodies that can “attack the mother”

562
Q

Granulocytes

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
  • multi-lobed nucleus
  • contains primary and secondary cytoplasmic granules
563
Q

Agranulocytes

A
  1. Lymphocytes
  2. Monocytes
  • contain only primary granules
564
Q

Neutrophils

A

60-70% of circulating leukocytes

- act to eliminate opsonized bacteria or limit the extent of an inflammatory reaction in connective tissue

565
Q

Eosinophils

A

2-4% of circulating leukocytes (can also enter connective tissue)

  • first defense against parasites
  • trigger bronchial asthma
566
Q

Basophils

A

1% of circulating leukocytes (can also enter connective tissue)

  • play roles in bronchial asthma and allergic skin reactions
567
Q

Lymphocytes

A

20-40% of circulating leukocytes

  1. B lymphocytes
  2. T lymphocytes
568
Q

B lymphocytes

A
  • Made in bone marrow
  • Antigen stimulated B cells differentiate into antibody secreting plasma cells
  • Mature in bone marrow
569
Q

T lymphocytes

A
  • Made in bone marrow
  • Participate in cell mediated immunity
  • Mature in thymus
570
Q

Monocytes

A

2-8% of circulating lymphocytes

  • circulate in blood for 12-100 hours then enter connective tissue
  • involved in bacterial phagocytosis, antigen presentation, and clean-up of dead cell debris
  • in bone, monocytes differentiate into osteoclasts
571
Q

Leukocyte adhesion deficiency I

A

Defect in beta subunit of integrin

  • leukocytes cannot leave blood vessels and enter tissues
  • clinically, inflammatory cell infiltrates are devoid of neutrophils
572
Q

Leukocyte adhesion deficiency II

A

Fucosyl containing ligands for selectin are absent

  • leukocytes cannot leave blood vessels and enter tissues
573
Q

Asthma

A
  • Mast cells degranulate and release chemical mediators, causing neutrophils and eosinophils to enter the connective tissue of the respiratory mucosa
  • eosinophils release additional factors to enhance bronchoconstriction which damage the cell lining and disturb mucociliary function
574
Q

Homing

A
  • Carbohydrate ligands on surface of neutrophil bind to selectin molecule expressed on endothelial cell
  • Integrin LFA-1 on surface of neutrophil binds to ICAM-1 on surface of endothelial cell
575
Q

Cell adhesion

A

Plays an important role in wound healing, immune surveillance, tumor metastasis and tissue morphogenesis

576
Q

Platelet formation

A
  1. Megakaryocytes develop cytoplasmic projections that become proplatelets
  2. Proplatelets fragment into platelets
577
Q

Platelets

A

Promote blood clotting and help to precent blood loss from damaged vessels

578
Q

Thrombocytopenia

A

Reduction in number of platelets in blood, leading to increased susceptibility to bleeding

  • caused by:
  • decrease in platelet production
  • increase in platelet destruction
  • aggregation of platelets in the microvasculature
579
Q

Bernard-Soulier Syndrome and von Willebrand’s disease

A

Inability of platelets to attach to subendothelial vascular surfaces

  • caused by deficiency in glycoprotein 1b-factor iX (von willebrand’s factor)
580
Q

Glycoprotein 1b-factor iX

A

von Willebrand’s factor

  • important in aggregation of normal platelets when they are exposed to injured subendothelial tissues
581
Q

Gray platelet syndrome

A

Autosomal dominant

Characterized by macrothrombocytopenia

582
Q

Macrothrombocytopenia

A

Reduced number of platelets in the blood, but remaining platelets in the blood have an increase in size/volume

583
Q

MYH9 related disorders

A

Associated with macrothrombocytopenia

  • Defect in myosin heavy chain IIA
  • causes defective formation of platelets during formation of proplatelets
584
Q

RBC lifespan

A

120 days, RBCs are constantly removed from circulation and replaced

585
Q

RBC function

A

Transport metabolic gases

  • O2 from lungs to the tissue
  • CO2 from tissue to lungs
586
Q

Erythropoisis

A

Hemocytoblast, proerythroblast, early erythroblast, late erythroblast, nomoblast, reticulocyte (can enter bloodstream), erythrocyte

587
Q

Hb synthesis

A

65% made before extrusion of nucleus

35% made in reticulocyte

588
Q

B12 and folic acid

A

Necessary for DNA synthesis

Deficiency would impact RBC’s and cause megaloblastic anemia

589
Q

Hemoglobin

A

Oxygen transporter

Tetramer of 2 alpha chains and 2 beta chains (4 subunits)

One heme per subunit

8- alpha helical segments that provide stability

590
Q

Heme

A
  • has iron atom (Fe2+/ferrous)
  • hydrophobic
  • carries O2
  • one per subunit (4 per molecule)
  • one molecule can carry 4 O2
591
Q

Hb F (Fetal)

A

2 alpha and 2 gamma subunit

592
Q

Adult HbA

A

2 alpha, 2 beta

593
Q

Adult Hb A2

A

Alpha 2

Delta 2

594
Q

Sickle cell anemia

A

Defect on beta gene of HbS at 6th position substituting valine for glutamic acid

-> polymerization of hemoglobin and sickle cell shape

Induction of expression of HbF can utilize gamma gene to help carry out the function of the defective beta gene

595
Q

Hemoglobin conformation states

A

Only 2

Oxy and deoxy

596
Q

Oxgen dissociation curve

A

Myoglobin (monomer) : hyperbolic curve

Hb (tetramer) : sigmoid shape

597
Q

Cooperativity

A

All hemes act together

  • all bind
    Or

-all unload

598
Q

2,3 BPG

A

Shifts Oxygen dissociation curve (ODC) to the right

  • more is produced at high altitude
599
Q

HbF

A

Fetal Hb has higher affinity for O2 than mother’s Hb

  • HBF does not bind well to 2,3-BPG
600
Q

HbF

A

Fetal Hb has higher affinity for O2 than mother’s Hb

  • HBF does not bind well to 2,3-BPG
601
Q

Iron transport in enterocyte

A

Dietary iron in Ferric form (Fe3+) is reduced to Fe2+ by Dcytb to enter the enterocyte

After being expelled from the enterocyte it is transformed back into Fe3+

602
Q

Transferrin

A

Carries iron to tissues where it is needed including bone marrow in a non-toxic form

*** On average, 30% of transferrin is bound to iron (transferrin saturation)

603
Q

TIBC high

A

Iron deficiency

604
Q

TIBC low

A

Fe overload

605
Q

Hereditary hemochromatosis

A

High TBIC

Organ dysfunction due to iron overload

606
Q

Megaloblastic macrocytic anemia

A

Deficiency in B12 and folate

  • large erythrocytes
  • nl Hb content in relation to size
607
Q

Vitamin B12

A

Cobalamin

Has Cobalt, protoporphyrin like ring, nucleotide, sugar, nitrogen ring

  • Accepts methyl from folate, releasing THF (FH4)
608
Q

Folic acid

A

Pteridine
PABA
Glutamate

609
Q

Tetrahydrofolate (FH4)

A

Becomes one-carbon donor for synthesis of nucleotides (methylene)

610
Q

Folic acid Pathway and B12

A

Deficiency in B12 will lead to deficiency in Folic Acid because N5-methyl-THF needs B12 to demethylate it in order to enter the folic acid cycle

611
Q

N5-methyl-THF

A

Primary circulating form of THF in bloodstream

” folate Trap”

612
Q

Intrinsic factor

A

Made by parietal cells of stomach, carries B12 to ileum where receptors bring it into body

613
Q

Proteases from pancreas

A

Degrade R-binder proteins in duodenum to release B12

614
Q

R-binder proteins

A

Made by gastric mucosa celss, bind to dietary B12 in stomach

615
Q

Transcobalamin II

A

Circulates through the blood carrying cobalamin

616
Q

Pernicious anemia

A

Lack of intrinsic factor causing Vitamin B12 deficiency

  • Pernicious means death
  • gastric mucosa is destroyed
  • decrease in IF
  • Use Schilling test
617
Q

Schilling test

A

Give oral Co-labeled B12 & inject B12

Collect urine in 24 hours

Cobalamin B12 not absorbed : pernicious anemia & part 2

B12 and radioactivity absorbed/seen in urine: B12 deficient diet is answer

618
Q

Normal absorption of B12 and radioactivity shows in urine

A

B12 deficient diet

619
Q

Cobalamin B12 not absorbed

A

Pernicious anemia

Give oral dose Co-B12 + IF

Collect urine in 24 hours

If radioactive B12 present: pernicious anemia due to lack of IF

620
Q

Pyruvate Kinase deficiency

A

No production of ATP in blood cells

621
Q

Transferrin saturation

A

Should be 30%

622
Q

Jaundice

A

Yellowing of skin/eyes

Excess bilirubin in blood stream (hyperbilirubinemia)

*imbalance between production and excretion of bilirubin

Can be pre-hepatic, intra-hepatic, or post-heaptic

623
Q

Biosynthesis of Heme

A

3 phases

1: Mitochondria
2. Cytosol
2. Mitochondria

624
Q

Phase I: heme biosynthesis

A

Glycine + Succinyl CoA -> ALA via ALA synthase

625
Q

Phase II heme biosynthesis

A

Condensation of 2 delta-ALA -> porphrobilogen

4 porphobilinogens -> coproporphyrinogen III

626
Q

Phase III heme biosynthesis

A

Coproporphyrinogen III install side-chain vinyl groups in protoporphyrinogen IX, which make ring system of protoporphyrin IX, Fe2+ is installed by ferrochelatase making heme

627
Q

Prophyrias

A

Caused by Defects in one or more stages of heme synthesis

Inherited metabolic disorders

  • hepatic -> neuological sx
    Erythropoietic -> skin phosensitivity
628
Q

ALA synthase

A

Needs pyridoxal phosphate

  • inhibited by heme and hemin
  • mRNA contains an iron response element
629
Q

Acute hepatic porphrias

A

Neurologic symptoms

630
Q

Erythropoietic porphyrias

A

Skin, photosensitivity

631
Q

Acute intermittent porphyriva

A

defect in PBG deaminase

  • hepatic

Excess ALA and PBG
Abdominal pain

632
Q

Congenital erythropoietic porphyria

A

Uroporphyrinogen III synthase defect, causes build up of Uroporphyrinogen I which is oxideized to uroporphyrin I (Bad)

-Erythropoietic

Photosensitivity,
Excess uroporphyrin I

633
Q

Porphyria cutanea tarda (PCT)

A

Defect in uroporphyrinogen decarboxylase

  • hepatoerythropoietic

**MOST common in US

Excess uroporpyrinogen III

634
Q

Variegate porphyria

A

Defect in protoporphyrinogen IX oxidase

  • hepatic

Photosensitivity, neurologic sx

635
Q

King George III

A

Variegate prophyria

636
Q

Reticulo-endothelial system

A

Degrades hemoglobin

Globin broken down into amino acids

Heme removed for degradation

637
Q

Heme oxygenase

A

Enzyme that removes bridge between pyrrole rings of heme

  • requires oxygen
  • releases Co2
  • iron oxidized from ferrous to ferric
  • synthesizes Biliverdin (green)
638
Q

Conjugation of bilirubin

A

Bilirubin released from spleen into bloodstream

  • binds to albumin because it is insoluble, and is then transported to liver

In hepatic microsomes, Bilirubin is conjucated with glucuronic acid to make direct BR which is soluble

639
Q

UDP glyconyl transferase

A

Enzymes in liver that conjugate free bilirubin with UDP-glucuronic acid make bilirubin-monoglucuronide and diuronide

640
Q

Urobilin

A

Yellow pigment in urine

641
Q

Stercobilin

A

Gives feces its brown color

642
Q

Pre-hepatic Jaundice

A

Increased production of unconjugated BR

Causes:

  • excess hemolysis
  • internal hemorrhage
  • capacity of liver uptake/excretion of BR is exceded
  • Glucose-6-PO4- dehydrogenase deficiency
  • Neonatal incompatibility of maternal-fetal blood

Findings:
*** ELEVATED blood levels or unconjugated or indirect BR

Direct BR is absent in urine
Urobilinogen present in urine
Nl AST and ALT
Nl blood levels of conjugated BR

643
Q

Intra-hepatic Jaundice

A

General liver dysfunction

  • impaired hepatic uptake, conjugation, or secretion of conjugated BR
  • Liver cirrhosis
  • hepatitis
  • Criggler-Najjar syndrome (conjugation defect)
  • Gilbert syndrome (conjugation defect)

Findings:

Increase in unconjugated and conjugated BR
Increase in ALT and AST
Nl urobilinogen levels in urine
Conjugated BR detected in urine

644
Q

post-hepatic jaundice

A

Problems with BR excretion (decreased bile flow)

  • Obstruction
  • Cholelithiasis
  • Liver disease
  • lesions
  • drugs

Findings:

ELEVATED blood levels of conjugated BR
Small increase in unconjugated form
Nl AST and ALT
Elevated bile salt levels
Conjugated BR in urine (dark color)
No urobilinogen in urine
No stercobilin in feces (pale)
Elevated alkaline phosphatase
645
Q

Neonatal Jaundice

A

akak Pysiological jaundice

  1. Breakdown of fetal hemoglogin
  2. Immature hepatic metabolic pathways
  3. Deficiency of UDP-GT enzyme
  • accumulation of excess BR in blood leads to jaundice
646
Q

Phototherapy

A

Used to treat jaundice, BR changes conformation to more soluble isomer when exposed to fluorescent light

647
Q

Crigler-Najjar syndrome Type I

A

Type I: complete abscence of the gene

  • deficiency of UDP-GT which conjugates BR
  • severe hyperbilirubinemia
  • encephalopathy in babies due to accumulation of BR in brain
648
Q

Kernicturus

A

Encephalopathy associated with BR accumulation in brain and Crigler-Najjar syndrome

649
Q

Criggler-Najjar Syndrome Type II

A

Benign form

  • mutation in UDP-GT gene, enzyme has less activity
650
Q

Gilbert syndrome

A

Reduced activity (25%) of UDP-GT

651
Q

Hepatitis

A

Liver inflammation leading to liver dysfunction

  • increased levels of unconjugated and conjugated BR in blood
  • jaundice
  • dark urine
652
Q

Heme color

A

Red

653
Q

Bilverdin color

A

Green

654
Q

Bilirubin color

A

Orange

655
Q

Hemosiderin (iron) color

A

Reddish brown

656
Q

Blood function

A
  1. Deliver requirements for cell metabolism
  2. Remove waste products
  3. Homeostasis
  4. Immune response
657
Q

Plasma

A

Consists of:

  • electrolytes
  • proteins
  • small organics
  • lipids
658
Q

Formed elements

A
  • WBC’s
  • RBC’s
  • Platelets
  • all arise from pluripotent stem cell
659
Q

Requirements for cell metabolism

A

Oxygen

Nutrients

660
Q

Remove waste products

A

Carbon dioxide

Metabolites

661
Q

Homeostasis

A

Hormones

Thermoregulation

662
Q

Cyanosis

A

Bluish/dark coloring of lips and skin

Result of hemoglobin in blood that doesn’t have enough oxygen associated with it

663
Q

Hematocrit

A

% of blood that is cells

664
Q

Erythropoiesis

A

Process of producing red blood cells

  • occurs in bone marrow
665
Q

RBC function

A

Deliver oxygen to tissue

  • Our bodies use the amt. of 02 getting to our tissues to determine how many RBC’s we need
  • this is sensed mostly in the kidney, but also in the liver
666
Q

Proteins in plasma

A
  • most made in liver
  • albumin
  • globulin
  • enzymes
667
Q

Enzyme systems

A
  • complement
  • kinin
  • clotting
  • fibronolytic
668
Q

What organ controls RBC production?

A

The kidney

669
Q

What happens if oxygen is low in the kidney?

A
  • HIF accumulates (hypoxia inducible factor)
  • HIF triggers erythropoietin in the kidney
  • RBC production occurs (Erythropoiesis)
670
Q

HIF

A

Hypoxia inducible factor

  • increases erythropoietin
  • increases transferrin
671
Q

Erythropoietin

A

Connects to JAK/STAT pathway

  • act on stem cell to increase differentiation into proerythroblasts and maturation rate
  • prevents apoptosis of erythroid stem cells
672
Q

Mutations in peptide chain

A

Change oxygen binding

673
Q

Requirements for adequate erythopoeisis

A
  • adequate general nutrition
  • iron availability
  • Vitamin B12
  • Folic acid
674
Q

Microcytic anemia

A

Iron deficiency, RBC’s are smaller than normal

675
Q

Oxygen capacity

A

Total amount of oxygen that can be carried in our blood assuming every available heme has an oxygen bound to it

1.34ml O2/ g hb x g hb/L blood

676
Q

Oxygen content

A

Amount of oxygen that is actually being carried in our blood

Oxygen capacity x % saturation

677
Q

Every gram of hemoglobin carries

A

1.34 mL of oxygen

678
Q

Oxygen % saturation

A

% of available hemes with oxygen bound

679
Q

ATP and RBC’s

A

Obtained via anaerobic glycolysis

  • Prevents oxidation of Hemoglobin
  • Maintains ferrous form of iron
  • ion transport
  • Membrane flexibility
680
Q

Hemolysis

A

Rupture of cell

681
Q

Methemoglobinemia

A

Presence of large amounts of iron in the Ferric (Fe3+) state in heme

682
Q

Phagocytosis

A

In spleen by macrophages

Hb is broken down

  • iron receycled
  • heme broken down to bilirubin
683
Q

Anemia

A

Decreased # of RBC’s

  • decreased Hb content
  • folate/B12 deficiency
  • iron deficiency
  • bone marrow damage
  • kidney damage

+ decreased oxygen capacity and content
+ decreased oxygen delivery to tissue
+ increased work load on heart
+ viscosity of blood is reduced

Oxygen saturation is unchanged

684
Q

Polycythemia

A

Excess RBC’s

More oxygen carrying capacity

+ increased viscosity of blood
+ increased cardiac effort
+ increased oxygen content and capacity

Oxygen saturation is unchanged

685
Q

Secondary polycythemia

A

Nl bone marrow
Kidneys respond to low oxygen levels due to

  • altitude (physiological polycythemia)
  • lung/heart disease
686
Q

Polycythemia Vera (primary polycythemia)

A

Bone marrow is making RBC’s when there is no need to (abnormal)

  • can be related to thrombopoietin receptor mutation

Erythropoietin levels are low

687
Q

Beta globin amino acid substitution and chromosome involved in sickle cell disease

A

Valine replaces glutamic acid on the surface of the beta chain in hemoglobin on chromosome 11

688
Q

Acute chest syndrome in kid with sickle cell disease

A

New pulmonary infiltrate on CXR

Respiratory distress

689
Q

Kids with sickle cell disease are particularly susceptible to:

A

Streptococcus pneumonia

690
Q

Splenic Sequestration crisis

A

Vaso-occlusion in the spleen secondary to sickle cells

  • spleen is rapidly enlarged and reticulocyte increases

MCM (2 decks)

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