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Foundations 1 > 8/9/17 and some 10 > Flashcards

8/9/17 and some 10 Flashcards

1
Q

Heme favor O2 relative to CO

A

Ligand constrained to bind in bent fashion, normal for O2 but not CO

CO only binds slightly better

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2
Q

Mb vs Hb

A

Mb a monomer, Hb a tetramer

Mb stores 02 while Hb transports it

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3
Q

O2 dissociation curves

A

Mb has higher oxygen affinity, reservoir for oxygen in skeletal muscles

Hb has sigmoidal curve that demonstrates cooperativity

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4
Q

T and R state

A

T is low oxygen

R is high oxygen

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5
Q

Proximal His

A

F8 from N terminus

His 87 each alpha helix

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6
Q

Oxygen binding

A

Fe2+ binds to proximal His and is above the plane of the ring

Oxygen pulls Fe2+ back into ring plane and moves the helix with the proximal His

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7
Q

Subunit interface interactions

A

Tetramer functions more so like a dimer of dimers

A1B1 = A2B2
A1A2
A1B2 = A2B1
B1B2

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8
Q

T state stabilization

A

A1B2 interface:
His B146 with Lys A40

A1A2:
His A122 with Asp A126

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9
Q

Allosteric Inhibitors of Hb

A

Shift dissoc curve right, more oxygen unloading in tissues

pH
Intracellular cons of 2,3-bisphosphoglycerate (BPG), binds to Beta subunits
CO2 binding to Hb

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10
Q

Bohr Effect

A

Effect of pH on Hb oxygen affinity

Only acid Bohr effect works

More acid means less oxygen bound

T state has greater affinity for protons than R state from His residues

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11
Q

Short term adjustment to high altitude

A

Up intra-erythrocytes conc. Of BPG

BPG comes from increased glycolytic activity

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12
Q

Role of inspire

A

Uncharged so pass into RBCs and converted to BPG to help increase the depleted levels

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13
Q

CO2 transport

A

Carbamoylation of the N terminal

Stabilizes T state over R

NOT by binding to heme

Carries CO2 from tissues to lungs, also does H+

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14
Q

Screening

A

Presumptive identification of unrecognized disease or condition by tests or other procedures

Perform on healthy people, not used for diagnostic

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15
Q

Types of disease prevention

A

Primary: prevent disease before it starts, before disease onset

Secondary: delay symptoms, onset to symptom appearance

Tertiary: slow disease progression, symptoms to death

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16
Q

Validity types

A

Internal: measure what supposed to

External: how well result generalize to rest of the population

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17
Q

Test sensitivity

A

Number of people who screen positive divided by the number of people actually with the disease

Optimize to prevent disease transmission

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18
Q

Test specificity

A

Number of peps who screen negative among those who actually don’t have the disease

Optimize for fatal disease with no treatment

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19
Q

Predictive values

A

Positive: peps with disease that tested positive divided by all positive tests

Negative: peps with disease that tested negative divided by all negative tests

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20
Q

miRNA

A

Regulate mRNA by degrade or inhibit translation if same or complementary to miRNA sequence

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21
Q

7SL RNA

A

Protein targeting

Forms ribonucleoprotein complex with 6 proteins to make signal recognition particle to move new protein to ER

22
Q

TATA box

A

TATA Binding Protein is part of TFIID

Cis-acting element that serves as a spot for a promoter to bind for increased transcription

TBP is saddle shape that bends DNA sharply

23
Q

Enhancer

A

Independent of distance of transcriptional start, IND of location, and IND of orientation

Segment of DNA that increases transcription

24
Q

Promoter

A

DNA that binds to RNA polymerase and controls transcription

Switch for on or off that can be positively or negatively regulated

25
Q

Trans-acting factor

A

Protein factor that binds to cigs-acting elements

26
Q

RNA polymerase for mRNA

A

Pol II, prokaryotes only have one pol for all RNA types

27
Q

Features of transcription

A

No primer is required, unlike DNA replication

Synthesized 5’ to 3’ and only use one strand of DNA for template

Template strand is the DNA strand that runs from 3’ to 5’

28
Q

Transcriptional start site

A

First nucleotide of Exon 1, upstream DNA would be the promoter

29
Q

Does RNA polymerase unwind DNA?

A

Yes, and then rewinds when move past

30
Q

PolyA addition

A

Endonuclease recognizes AAUAAA and cleaves RNA downstream

Polyadenylate polymerase then adenylates the residue

31
Q

Genomic imprinting

A

Methylated CpG of one parental allele

Cytosine is methylated in CpG

Look at last slide of 2nd articulate on Thursday 8/10

32
Q

mRNA stability for post-transcriptional regulation

RBC

A

When cellular iron conc. Is low, protein binds to 3’ end of transferrin receptor mRNA and prevents it from being degraded, results in increased iron conc.

33
Q

Translational regulation of RBCs

A

Globin protein synthesis is regulated by the heme conc.

Regulated at initiation of translation
Little heme means little globin synthesis

34
Q

What explains X inactivation?

A

DNA methylation

35
Q

Actinomycetes D

A

Intercalated in DNA so bad template for RNA synthesis, transcription inhibitor

Works in both prokaryotes and eukaryotes

36
Q

Rifamyacin or rifampicin

A

Interferes with formation of first phosphodiester bond , inhibit initiation of RNA synthesis

Only affects prokaryotes

37
Q

Alpha-amanitin

A

Binds to RNA Pol II so blocks eukaryotic transcription

Mushroom

38
Q

Prokaryotic protein synthesis inhibitors

Inhibit translation

A

Tetracycline: block A site and inhibits binding of charged tRNA

Chloramphenicol: inhibits peptidyl transferase activity

Erythromycin: binds to 50S subunit and inhibits translocation

Streptomycin: causes misreading and inhibits translation

Neomycin, kanamycin, gentamycin: interferes with 16S rRNA

39
Q

Both Prokaryotic and Eukaryotic protein synthesis inhibitors

Inhibit translation

A

Structure similar to the 3’ end of an amino-acyl tRNA, binds to empty A site, peptide with puromycin at C terminus

40
Q

Eukaryotic protein inhibitors

Inhibit translation

A

Cycloheximide: blocks peptidyl transferase activity

Diphtheria toxin: 2 polypeptides covalently modify translocase to inactivate translocation, immunization against this bacterial toxin is universal in US

Ricin: inactivated the 60S subunit of the eukaryotic ribosome

41
Q

Systemic lupus erythematosus

SLE

A

Auto-immune disease that causes chronic inflammation, snRNPs are targets of the antibodies

Joint pain and swelling, butterfly rash on cheeks

42
Q

Testicular feminization

A

XY with androgens

Lack androgen receptor

Man boobs

43
Q

Chronic myeloid nous leukemia

A

Translocation between chromosomes 9 and 22, Philly Chromosome

Cancer of white blood cells

44
Q

Methotrexate

A

Treats cancer by inhibiting dihydrofulate reductase to produce inadequate amount of thymine and stop cell proliferation

Resistance by gene amplification of DHFR gene to dampen the effects of competitive inhibition

45
Q

Vitamin deficiency anemia

A

Vitamin B12 for Hemoglobin production is needed

46
Q

Hemolytic anemia

A

Destruction of RBCs for various reasons

47
Q

Aplastic anemia

A

Rare, bone marrow fails to produce all types of blood cells

48
Q

HbS Polymerization factors

A

Intracellular Hb composition, higher % of HbS has higher polymerization

Intracellular Hb conc., higher HbS conc. Has greater polymerization, dehydration makes worse

Oxygenation, polymerization favored at low oxygen saturation, acidosis promotes polymerization cuz makes HbS deoxygenation

49
Q

Clinical manifestations of sickle cell

A

Anemia, frequent infections, joint pain, dyspnea, leg lesions heal poorly, vaso-occlusive crises, severe pain

50
Q

Short term sickle cell treatments

A

Hydration, oxygenation, narcotic analgesics, exchange transfusions, antibiotics

51
Q

Long term sickle cell treatments

A

Iron chelators, hydroxyurea, bone marrow transplantation, antioxidants, gene therapy

52
Q

Inosine

A

Converted to BPG in cell

Used for stored blood

Foundations 1 (19 decks)

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