lecture 5 Flashcards

1
Q

catabolic processes involve

A

glucose fatty acids, & amino acids

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2
Q

tricarboxylic citric acid cycle

A

TCA, Krebs

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3
Q

citric acid cycle is

A

amphibolic with roles in both catabolism and anabolism

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4
Q

citric acid cycle is a central pathway for

A

recovering energy from several metabolic fuels

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5
Q

citric acid cycle intermediates can also serve as

A

precursors for biosynthetic pathways

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6
Q

anaplerotic reactions

A

reactions that replenish intermediates depleted by other reactions

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7
Q

anabolic use of TCA cycle intermediates

A

gluconeogenesis
lipid biosynthesis
amino acid biosynthesis
porphyrin biosynthesis

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8
Q

gluconeogenesis

A

malate -> OAA->-> glucose

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9
Q

lipid biosynthesis

A

citrate-> OAA + Acetyl CoA->-> lipids

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10
Q

Amino Acid biosynthesis

A

OAA and alpha-ketoglutarate

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11
Q

poryphyrin biosynthesis

A

succinyl CoA

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12
Q

TCA cycle takes place in the

A

mitochondria

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13
Q

outer membrane

A

permeable to anything smaller than 5 kD

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14
Q

inner membrane

A

permeable to only O2, H2O and CO2

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15
Q

what do the membranes do

A

transport proteins required for everything else

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16
Q

pyruvate from glycolysis is split

A

acetyl group added to coenzyme A
-generates one NADH
-generates one CO2

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17
Q

Acetyl-CoA combines with oxaloacetate to form citrate

A

citrate enters the “cycle”

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18
Q

one 2-Carbon acetyl group of citrate is oxidized

A

-eight reactions
-produces 2 CO2
-produces 3 NADH, 1 FADH2
-1 GTP/ATP
-regenerates oxaloacetate

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19
Q

preparation : generation of Acetyl-CoA

A

Coenzyme A(CoA-SH)
derived from B-vitamins

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20
Q

Coenzyme A recieves 2 carbons from pyruvate in form of acetyl group

A

“high energy” thioester linkage
multi-enzyme process

21
Q

catalyzed in 5 sequential reactions

A

oxidative decarboxylation
pyruvate dehydrogenase complex (E 1,2,3)
large negative delta G
produces CO2

22
Q

pyurvate dehydrogenase multienzyme complex is totally awesome

A

multiple copies of 3 enzymes
pyruvate dehydrogenase
dihydrolipoyl transacetylase
dihydrolipoyl dehydrogenase
Ca. 25 nm

23
Q

E1 pyruvate dehydrogenase

A

uses thiamine pyrophosphate (TPP) as co-factor
attacks carbonyl C2 of pyruvate, releases CO2
TPP remains bound to hydroxyethyl group

24
Q

lipolamide arm of dihydrolipoyl transacetylase

A

Lipoic acid: cofactor covalently bound to Lys of E2
creates long, flexible rm can move between active sites of all 3 PDH enzymes
disulfide bond can be reduced to SH + SH
can serve as electron carrier and acetyl carrier

25
Q

lipoic acid

A

cofactor covalently bound to Lys to E2

26
Q

E2: Dihydrolipoyl transacetylase

A

lipo side chain extends to E1
transfers hydroxyethyl from TPP to dihydrolipoamide
partial reduction creates acetyl group
second reduction transfers acetyl group to CoA

27
Q

generation of Acetyl CoA

A

CoA recieves 2 carbons from pyruvate in form acetyl group
“high energy” thioester linkage

28
Q

E3 dihydrolipoyl dehydrogenase resets the system

A

catalyzes the regeneration of disulfide(oxidized) form of Lipomide/lipolysine
-Uses bound cofacter FAD (reduced to FADH2)

29
Q

NAD+ oxidizes FADH2 to regenerate FAD

A

NAD becomes reduced (NADH +H+)

30
Q

PDH enzyme complex is regenerated

A

NADH and H+ are made

31
Q

PDH “substrate channeling”

A

intermediates never leave the complex tethered by lipoamide arm

32
Q

acetyl CoA is also derived from fatty acids

A

thiol group of CoA-SH caries out nucleophilic attack
step one: creating a fatty acyl-CoA

33
Q

step 2 beta-oxidation

A

each 4-step “pass” removes one acetyl group (2 C) from chain to make Acetyl CoA
also makes FADH2 and NADH/H+

34
Q

formation of citrate from acetyl CoA and oxaloacetate

A

methyl C of acetyl group group is joined to carbonyl C of OAA
free CoA- SH (reduced) goes back to PDH complex

35
Q

2 formation of isocitrate from citrate A 2-step process

A

positive delta G
transfers C2-OH of citrate to C3
formation of cis-aconitate C2-C3 double bond intermediate (tricarboxylic acid)

36
Q
  1. Oxidation of isocitrate
    a 3- step oxidative decarboxylation
A

initial oxidation produces oxalosuccinate intermediate
-produces first NADH (or NADPH)

37
Q

decarboxylation gives alpha-ketogluterate

A

-enol intermediate gets rearranged
-produces first CO2
manganese ion in enzyme active site helps stabilize intermediates

38
Q

4 Oxidation of alpha-ketogluterate

A

alpha-ketogluterate dehydrogenase complex

very similar to pyruvate dehydrogenase
-multi-enzyme complex , TPP, FAD, NAD cofactors
-produces succinyl-CoA instead of acetyl-CoA
-produces second NADH, second CO2

39
Q
  1. Conversion of Succinyl-CoA to succinate
A

succinylcholine- Co synthetase
produces GTP or ATP ( depends on S-CoA-synth isozyme) and CoSH
energy released in breakage of thioester bond drives GTP/ATP formation
net delta G is -2.9 kJ/mol

40
Q
  1. Oxidation of succinate
A

succinate dehydrogenase
FAD covalently bound to enzyme, along with Fe-S centers
-electrons flow from FAD-Fe/S - ETC
-ultimately leads to ATP production (oxidative phosphorylation)

succinate dehydrogenase is embedded in inner mitochondrial membrane

41
Q
  1. hydration of fumarate
A

H2O added across fumarate double bond
only works with transfumarate (not cis)

42
Q
  1. oxidation of malate
A

malate dehydrogenase
hydride ion transfer from malate to NAD+ makes 3rd NADH
regenerates OAA for another cycle

43
Q

products of the citric acid cycle

A

3 NADH
1FADH2
1 GTP/ATP
2CO2

44
Q

citric acid cycle regulation: regulated at the three exergonic steps

A

rate limiting steps(-delta G)

45
Q

citrate synthase:

A

-inhibited by citrate NADH and succinyl-CoA

46
Q

isocitrate dehydrogenase

A

inhibited by ATP, NADH
activated by CA2+ and ADP

47
Q

alpha-ketogluterate dehydrogenase

A

inhibited by NADH and succinyl-CoA
Activated by Ca2+

48
Q

citric acid cycle regulation

A

ATP, NADH acetyl-CoA = inhibitory
ADP, NAD+, CoA, Ca2+ = stimulatory
regulated at the three exergonic steps