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Flashcards in Deevska Review Deck (82):
1

General mechanism of regulation of gene expression in prokaryotes

-Major level of regulation is transcription

2

The general mechanisms of regulation of gene expression in eukaryotes

1. Transcription
2. Post-transcription
3. Translation
4. Post translation

Epigenetics

3

What allows for more sophisticated regulation in eukaryotic cells compared to prokaryotic cells

Eukaryotic cells have nucleus separation, which allows for more sophisticated control

4

Repressor operon

Suppress the transcription of a gene. Transcription is usually on, but can be inhibited

5

Inducible operon (activators)

Transcription usually off, but can be stimulated

6

Structure of operon

-control region
-structural region

7

Control region of operon

Contains promoter and operator.
-different factors/molecules that activate/inhibit to regulate (always expressed)

8

Structural genes on operon

Sequence one after another
-genes required to make AA
-all necessary to code for enzymes
-all controlled by ONE regulator

9

Lac operon in general

-inducible
-E. coli prefers glucose
-it can use other sugars such as lactos, however, this requires more enzymes (hence more energy) so E coli only produces the enzymes to use other sugars if glucose is absent and another sugar is present

10

Repressor protein for lac operon when glucose only is present

-encoded by the lac1 gene, always present and bound to the operator, blocks RNA polymerase

11

Lac operon when glucose is absent

Adenyly cyclase makes cAMP, CAP, cAMP complex forms, binds to CAP binding site, RNA polymerase can efficiently initiate transcription

12

Lac operon when lactose is present

A small amount of allolactose is produced that binds to the repressor and prevents it from binding to the operator

13

What role does allolactose have in lac operon function

Binds to the repressor, and prevents it from binding to the operator, lac operon is on

14

When glucose is present

It inhibits adenyly cyclase, no cAMP, cannot form CAP/cAMP complex, cannot initiate transcription

15

What happens when there is both glucose and lactose present for the lac operon?

Although the repressor is inactive, the transcription can not be initiated because the cap site is empty. Even though a small amount of allolactose binds to the repressor, the CAP site is still empty due to the lack of glucose, so RNA polymerase cannot efficiently initiate transcription

16

What is the level of gene expression control that is common between prokaryotes and eukaryotes?

Transcription

17

Cis-acting elements,

Regulation of transcription is controlled by the regulatory sequences of DNA which are usually embedded in the noncoding regions of the genome. They are called this because they influence expression of genes only on the same chromosome

18

Trans-acting regulators

Capable of interacting with regulatory molecules (transcription factors). Transcription not possible without these
They are proteins

19

Enhancers

DNA sequences that increases the rate if initiation of transcription
- on same chromosome
-can be close or far from gene
-upstream or downstream or within intron regions
-tissues specific manner

20

How can enhancers be brought close to the basal promoter

By bending of the DNA molecule

21

Transcription factors (trans acting)

-DNA binding domain
-activation domain-stabilize formation of the initiation complex, recruit chromatin modifying proteins

22

PEPCK inhibited by cortisol

-cortisol diffuses into cytosol
-binds to intracellular receptor
-complex enters nucleus
-binds to GRE
-PEPCK transcription is induced

23

Alternative splicing and gene expression

-tissue specific isoforms of proteins can be made from the same pre mRNA by the use of alternative splice sites
-over 60% of the genes in humans undergo alternative splicing
-tropomyosin

24

MRNA editing and gene expression

-additional posttranscriptional modification in which a base in the mRNA is altered
-Apo B mRNA, in the intestine only, the C residue in the CAA codon for glutamine is deaminated to U, changing the sense codon to a nonsens or stop codon

25

RNAi and gene expression

-mechanism of reducing gene expression by repressing translation or increasing the degradation of specific mRNAs
-cell proliferation, differentiation, apoptosis
-therapeutic potential

26

RNAi and ARMD

AMD is triggered by VEGF, an siRNA designed to target the mRNA of VEGF and promote its degradation went to clinical trials (1st approved for clinical trials )

27

Translational control

-eIF-2: phosphorylation of this inhibits translation at the initiation step
-does so by inhibiting GDP to DTP exchange
-phosphorylation catalyzed by kinases in response to environmental conditions

28

Post translational control

1. trimming
2. Covalent attachment (phosphorylation)
3. Protein folding (chaperones)
4. Protein degradation (ubiquination)

29

Epigenetic regulation

-Euchromatin-loosely packed accessibly for transcription
-Heterochromatin-tightly packed, inaccessible
-methylation of DNA and histones cause nucleosomes to pack tightly together. Transcription factors cannot bind the DNA and genes are not expressed
-histone acetylation results in loose packaging of nucleosomes, genes expressed

30

CpG islands

Regions in DNA rich in CG that are prone to modifications

31

Transposons

-mobile segments of DNA that move in a random manner from one site to another on the same or a different chromosome
-direc-cuts out and reinserts
-replicative- copied and inserted elsewhere
-rare cases of hemophilia A, Duchenne muscular dystrophy, antibiotic resistance

32

What is the urea cycle?

A cycle of biochemical reactions occurring in that produces urea from ammonia

33

Where does the urea cycle take place?

Primarily in the liver, and to a lesser extend in the kidney

34

What is the immediate precursor for ammonia and aspartate?

Glutamate

35

Thermogenics of urea cycle

ATP is used
Irreversible
Large -deltaG

36

Where doe the nitrogens of the urea cycle come form?

-one from free NH3 and one from aspartate

37

Purpose of urea cycle

Get rid of nitrogen in form of free ammonia in dehydration of AA. Cannot store AA. 1st step is removing alpha-amino group, producing ammonia. Excreted into kidney, urea operates in liver mostly, some kidney

38

Sources of ammonia

-diet
-glutamine
-bacterial action
-amines
-catabolism of purines and pyrimidines

39

Free ammonia present in circulation

Will be removed by the liver and used for the synthesis of urea

40

What contributes to the acid-base balance of the body by excreting protons?

Free ammonia released in the urine

41

Glucogenic

An AA that can be converted into pyruvate or an intermediate of the TCA cycle
-may be used as substrates for gluconeogensis
-rise to a net increase in glucose formation in the liver
-pyruvate

42

Ketogenic

AA that can be converted into acetoacetate or a precursor
-acetyl-CoA

43

Elevated homocysteine

Produced during methionine metabolism

44

Elevations in plasma homocysteine

Promote oxidative damage, inflammation, and endothelial dysfunction and are an independent risk factor for occlusive vascular disease

45

Elevated Hcy during pregnancy

Associated with increases incidence of neural tube defects

46

Eye abnormalities of Hcy

-ectopia lentis
-myopia
-glaucoma
-optic atrophy
-retinal detachemtn
-cataracts

47

Albinism

Tryptophan to melanin defect
Lack pigment
High risk of skin cancer

48

What is homocysteinuria a deficiency of?

Cystathionine synthase

49

What are the two major pathways in which alcohol is processed in the liver?

-ADH (alcohol dehydrogenase)
-MEOS relying on cyt P450 enzymes

50

What is rate limiting in alcohol metabolism

ADH

51

Asians and alcohol metabolism

Mutation for dominant negative mutation
- heterozygotes who still produce the normal enzyme in addition to the defective one, have newer zero enzyme activity

Atypical ALDH

52

DIsulfiram

-Antabuse
-Accumulation of acetaldehyde after ingestion of ethanol
-Deterrent
-inhibits aldehyde dehydrogenase

53

What is the most toxic intermediate in ethanol metabolism?

Acetaldehyde

54

What are symptoms of acetaldehyde toxicity

Flushing of the face and nausea

55

What has a more immediate affect on ethanol metabolism

NADH

56

The processing of alcohol produces large quantities of_______ in the liver

NADH

57

Large amounts of NADH

Alter many metabolic processes
-inhibits many enzymes

58

Significant effects of NADH build up found in...

Mainly in heavy drinkers and occasional drinkers that binge

59

Build up of NADH in well fed state

NADH will inhibit PDH complex and cause pyruvate to be converted into lactate resulting in lactic acidosis

60

Secondary affect of lactic acidosis

Underexcretion of uric acid, hyperuricemia

61

Hypoglycemia and ethanol metabolism

In the fasting state, the liver will try to perform GNG, however precursors will be diverted at pyruvate to the production of lactate. If the liver glycogen stores become depleted, it will result in hypoglycemia
-can happen to anyone

62

Is alcohol ketogenic of glucogenic?

Ketogenic

63

Hyperlipidema and fatty liver

High levels of NADH inhibit the oxidation of fatty acids.
-results in accumulation of TAG as lipid droplets leading to fatty liver
-some of it is releases into the bloodstream as VLDVLs causing hyperlipidemia

64

Folate deficiency in ethanol metabolism

Results in megaloblastic anemia

65

Thiamine deficiency in ethanol metabolism

Wernicke-korsakoff syndrome

66

What are alcoholics usually deficient in?

Folate and thiamine

67

G1 of cell cycle

Active metabolism and accumulation of building blocks and energy
-cellular metabolism happens here

68

G2 of cell cycle

Active metabolism and protein synthesis; duplication of organelles
-produces macromolecules
-organelles duplicated

69

G0 of cell cycles

-resting
-period in the cell cycle in which get cell exists in a quiescent state; the cell is neither dividing nor preparing to divide
-some are capable of going back into the cell cycle

70

G2 checkpoint

Check for
-cell size
-accurate DNA replication

71

M checkpoint

Check for
-chromosome attachment to the spindle

72

G1 checkpoint (restriction)

Check for:
-cell size
-nutrients
-growth factors
-DNA damage

73

What are the checkpoints of the cell cycle

G2 checkpoint
M checkpoint
G1 checkpoint

74

Positive regulation of the cell cycle

Cyclins and Cdk
-changes of different cyclins through the cell cycle
-direct correlation between cyclin accumulation and the three major cell cycle checkpoints
-sharp decline of cyclin levels following each checkpoint
-cyclins only active when bound to Cdk

75

Negative regulators of cell cycle

-Rb
-P53
-p21

76

Rb

Retinoblastoma protein
-retinoblastoma protein; prevents initiation of the cell cycle in G1 phase

77

P53

-transcriptional repressor
-repress transcription and promote apoptosis
-induces cell cycle arrest
-checks for DNA damage, cell cycle abnormalities, hypoxia

78

P21

-prevents cell cycle progression by
-inhibiting the activity of cyclin E-associated CDK2
-therefore preventing E2F-mediated gene transcription and cell cycle progression

79

Oncogenes

Positive regulators of cell cycle mutated

80

Protooncogenes

Not mutated, + cell cycle regulated

81

Tumor suppressor genes

Genes that encode for negative regulator proteins that will suppress uncontrolled cell division
Rb, p53, p21

82

Role of p53 in cancer

If it is mutated, it will not arrest cell cycle when it comes across cell abnormalities, the damaged cell will continue to divide which results in cancer