Metabolic Control L18 Flashcards

1
Q

what are the main biochemical pathways in the cell

A
Carbohydrates
Amino Acids 
Lipids
Purines and Pyrimidines
Vitamins and coenzymes, hormones
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2
Q

why must the cell regulate biochemical pathways

A

provide products in pathway at the rate they are needed

maintain the steady state concentrations of metabolites within a narrow range (homeostasis)

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3
Q

why must the cell regulate homeostasis

A

Large changes in metabolites may have deleterious effects on cells
Intermediates needed for several pathways need a delicate control
Need for rapid response to changes in supply or demand (e.g. response to hormones)

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4
Q

what are the four different levels of regulation in the cell

A

modulation
interconversion
changes in enzyme biosynthesis
compartmentalisation

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5
Q

what is the regulation of modulation

A

Rapid but modest changes in enzyme activity in response to fluctuating levels of metabolites

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6
Q

what is the regulation of interconversion

A

Slower but larger scale activation of suppression of pre–formed enzyme ‘pools’

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7
Q

what is the regulation of changes in enzyme biosynthesis

A

Slow but major changes in gene expression via

  • Transcription of DNA into mRNA
  • Translation of mRNA into protein
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8
Q

what is the regulation of compartmentalisation

A

Restricting the access of enzymes to substrates via regulating transport in and out of mitochondria, nuclei, endosomes, membranes etc

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9
Q

what are all the cell regulations related to

A

enzyme activity

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10
Q

how long does enzyme synthesis/degradation take

A

hours

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11
Q

how long does enzyme modification take

A

mins to seconds

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12
Q

how long does enzyme activity take

A

milliseconds

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13
Q

what is modulation

A

control of enzyme activity by inhibitors/activators

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14
Q

which enzymes act as control points

A

enzymes catalysing irreversible reactions

enzymes at the start of the pathway

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15
Q

what is feedback inhibition

A

Decrease the activity of the enzyme, decrease the rate of the products made – less ATP production
When need more ATP the inhibition is removed

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16
Q

what is branch point inhibition

A

enzymes in bacterial amino acid metabolism are subject to a range of feedback inhibition strategies
If one amino acid is low, will feedback and stimulation production of that particular part of the pathway
Some branch point enzymes have several isoforms, each with different feedback regulators

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17
Q

what is interconversion

A

reversible transformation of one enzyme form into another, typically with an alteration in the enzyme activity
modification either activates or inhibits enzyme activity

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18
Q

what is used to convert glucose to glucose-6-phosphate

A

hexokinase

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19
Q

what is used to convert glucose-6-phosphate to glucose-1-phosphate

A

using phosphoglucomutase

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20
Q

what is used to convert glycogen-1-phosphate to glycogen

A

glycogen synthase

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21
Q

what is used to convert glycogen to glucose-1-phosphate

A

glycogen phosphorylase

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22
Q

what glucose is released to be used

A

glucose-1-phosphate

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23
Q

which glycogen phosphorylase is inactive, why

A

Glycogen phosphorylase b as no phosphate group

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24
Q

what causes glycogen phosphorylase to be converted to phosphorylase a isoform, effect

A

response to a hormonal signal glycogen phosphorylase b is converted to the phosphorylase a ISOFORM and permanently activated

25
Q

what happens in glycogen metabolism to make G-1-P

A

glycogen synthesase inactive due to the adrenaline

adrenaline activates glycogen phosphorylase

26
Q

what regulates these enzymes in glucose metabolism

A

Adrenaline

27
Q

what does phosphorylase b use to be converted to a

A

phosphorylation step requires ATP + the enzyme phosphorylase kinase

28
Q

how many protein kinases are there

A

~520 protein kinases

29
Q

what is needed to remove phosphate by hydrolysis

A

specific protein phosphatases

30
Q

what bond is stable even during protein isolation

A

covalent phospho-serine, -threonine and -tyrosine bond

31
Q

what transfers the terminal phosphate of ATP to the hydroxyl groups of ser, thr, tyr

A

specific protein kinases

32
Q

what happens in signal transduction cascade

A

Hormone can stimulate production and release of protein kinase A
Protein kinase A converts phosphorylase b kinase to hav a phosphate
phosphorylase b kinase with phosphate converts phosphorylase b to phosphorylase a

33
Q

what happens in signal transduction

A

set of chemical reactions in a cell that occurs when a molecule, e.g. hormone, attaches to cell membrane receptor
pathway is a cascade of biochemical reactions inside cell that eventually reach target molecule or reaction

34
Q

where is glycogen stored

A

muscles

35
Q

what happens in signalling transduction pathway

A
  1. Adrenaline cannot enter the cell need to bind to receptors on the membrane, when bind they have to stimulate a secondary hormone cAMP
  2. when adrenalin binds to receptor adenylate cyclase is activated
    cAMP stimulated by adenylate cyclase
  3. Activates Protein Kinase A
  4. Cascade to activate glycogen phosphorylase
36
Q

how can protein kinase a affect gene expression

A

by phosphorylating a transcription factor

37
Q

how can other hormones or growth factors affect gene expression

A

other hormones or growth factors can affect gene expression via Ca++ and/or Protein Kinase C

38
Q

what is the control of gene expression

A

transcription and translation

39
Q

what is the control of gene expression in a eukaryotic cell

A

DNA to RNA first level of control (transcriptional control)
RNA transcript to mRNA (RNA processing control)
mRNA to protein (translation control)
protein to inactive protein (protein activity control)
Can intervene at these points of control

40
Q

how is control of gene expression mainly controlled

A

through initiation of transcription

  • Structure of gene
  • Interaction with RNA polymerase (form pre initiation complex PIC)
41
Q

how are totipotent genes controlled in gene expression

A

Majority of cells contain full complement of DNA
Different tissues express different genes, due to the transcription factor they originally express, it determines the function of the cell

42
Q

what are the RNA polymerases needed to initiate transcription

A

Poly I
Poly II
Poly III

43
Q

what does Poly I used in

A

rRNA

44
Q

what is Poly II used in

A

mRNA

45
Q

what is Poly III used in

A

tRNA and 5rRNA

46
Q

what is the role of polymerase in gene expression

A

binds to the promoter of the gene, which impact on what genes are expressed and what proteins are made

47
Q

what are the consensus sequences in prokaryotes

A

TATA box

48
Q

what are the consensus sequences in polymerase II dependent promoters of eukaryotes

A

TATA box
CAAT box
GC box

49
Q

what is the TATA box

A

TATAAAA

50
Q

what is the CAAT box

A

GGNCAACT

51
Q

what is the GC box

A

GGGCGG

52
Q

what are the transcription factors that polymerase requires for transcription initiation

A

TFIIA
TFIIB
D
E

53
Q

what is the order that polymerase and the four other factors bind

A
  1. TFIID, binds directly to the TATA box promoter region
  2. TFIIA binds with TFIID that is already bound to the TATA box
  3. TFIIB then binds and facilitates RNA polymerase II to bind
  4. TFIIE binds to form the preiniation complex and trigger the beginning of transcription at the initiation point (start point
54
Q

why can’t polymerase initiate transcription without the other four factors

A

does not recognise the promoter and it requires four other factors to initiate transcription from a TATA box promoter region

55
Q

what is formed in initiation of transcription

A

basal transcription complex

56
Q

what are enhancers

A

sequences far from the promoter that proteins can bind to

57
Q

what effect do proteins binding to DNA sequence have

A

can activate or repress transcription

58
Q

what is the structure of transcription factors

A

often homo- or hetero-dimers

they can also have several domains

59
Q

what may the activation domain have

A

can include ligand binding sites – interaction with signal molecules