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POM 2: Molecular biology of the cell > 1: Cell metabolism and integrity > Flashcards

1: Cell metabolism and integrity Flashcards

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1
Q

Glycolysis

A

2 stages -
forming high energy compound
splitting a high energy compound

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2
Q

Where does glycolysis occur

A

Cytoplasm

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3
Q

Glycolysis is

A

Anaerobic
Converts one molecule of glucose into two pyruvate molecules

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4
Q

Isomerase enzymes are used for

A

making an isomer

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5
Q

Kinase enzymes are used for

A

movement of a phosphate group (generally)

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6
Q

First step of glycolysis

A

Glucose –(hexokinase)–> glucose-6-phosphate

irreversible reaction, commits glucose to glycolysis
uses ATP in order for reaction to start

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7
Q

Fructose bisphosphate splits into

A

via Aldolase
DHAP (dihydroxyacetone phosphate)
into
G3P (glyceraldehyde-3-phosphate)
via TPI
-2 molecules from now on-

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8
Q

Net result of glycolysis

A

2 pyruvate molecules
Net gain of 2 ATP
2 NADH

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9
Q

Pentose Phosphate Pathway

A

When ATP isn’t needed, glucose enters PPP
produces Ribose or NADPH

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10
Q

NADPH produced by the PPP

A
  • electron rich
    involved in antioxidant reactions:
    RBCs produce Reactive Oxygen Species and glutathione
    NADPH is an electron supplier for glutathione
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11
Q

3 fates of pyruvate

A

Alcoholic fermentation
Lactate production
(Regenerate NAD+ for glycolysis to continue) - Anaerobic processes

Acetyl CoA production (create Acetyl CoA to enter TCA cycle)
-Aerobic process

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12
Q

Pyruvate in alcoholic fermentation

A

Pyruvate –(pyruvate decarboxylase)–> acetaldehyde –(alcohol dehydrogenase)–> ethanol

occurs in yeast, anaerobic process
NAD+ regenerated for glycolysis

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13
Q

Pyruvate in lactate production

A

pyruvate–(lactate dehydrogenase)–> lactate

  • used in muscles during intense activity
    NAD+ regenerated
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14
Q

Pyruvate in Acetyl CoA Production

A

Pyruvate –(pyruvate dehydrogenase complex)–> acetyl CoA + CO2

  • occurs in mitochondria
  • acetyl CoA enters TCA cycle
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15
Q

Beri Beri is

A

Thymine deficiency
(Vit B1)
(thymine needed to form TPP - prosthetic group forming pyruvate dehydrogenase complex)
less TPP=less ATP prod.

Loss of H+, carbanion attacks pyruvate
cannot convert pyruvate into acetyl CoA
so cannot enter TCA cycle

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16
Q

Symptoms of Beri Beri

A

damage of peripheral nervous system
muscle weakness
Decreased cardiac output
BRAIN particularly vulnerable

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17
Q

TCA cycle occurs in the

A

mitochondria

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18
Q

Each TCA (Krebs) cycle produces

A

2x CO2
3x NADH
1x GTP
1x FADH2

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19
Q

Where are TCA cycle enzymes found

A

Soluble proteins found in mitochondrial matrix space
except for succinate dehydrogenase (inner mitochondrial membrane)

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20
Q

Glucogenic amino acids

A

amino acids which eventually form glucose

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21
Q

Ketogenic amino acids

A

amino acids which eventually enter Krebs cycle as Acetyl CoA

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22
Q

How many amino acids are there

A

20

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23
Q

How many molecules do amino acids give rise to

A

7
pyruvate
Acetyl CoA
Acetoacetyl CoA
a-ketoglutarate
Succinyl CoA
Fumarate
Oxaloacetate

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24
Q

two groups of amino acids

A

Glucogenic
Ketogenic

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25
Q

Transamination reaction

A

Transferral of amino group

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26
Q

Transamination reaction of alanine and a-ketoglutarate

A

forms : pyruvate (alanine) (acetyl CoA enters krebs) and glutamate (re-converted to a-kg)
Alanine undergoes transamination by action of alanine aminotransferase enzyme

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27
Q

Role of NADH

A

enter mitochondrial matrix to regenerate NAD+
used in oxidative phosphorylation in mitochondria

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28
Q

How does NADH form NAD+

A

NADH moved into mitochondria, oxidised in electron transport chain, NAD+ moved out of mitochondria

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29
Q

NADH shuttles

A

Glycerol phosphate shuttle - brain, skeletal muscle
Malate-aspartate shuttle - liver, kidney, heart

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30
Q

Process of glycerol phosphate shuttle

A
  1. Cystolic glycerol 3-phosphate dehydrogenase transfers electrons from NADH to DHAP to generate glycerol 3-phosphate
  2. Glycerol 3 phosphate carries electrons
  3. Membrane bound form of same enzyme transfers electrons to FAD, then get transferred to co-enzymeQ part of e- transport chain
  4. G3-phosphate drops off electrons becoming DHAP again
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31
Q

Malate Aspartate Shuttle

A

aspartate converted to oxaloacetate using AT (aspartate transaminase)
oxaloacetate converted to malate using MDH (malate dehydrogenase)
then enters mitochondria using malate-a-ketoglutarate antiporter
REVERSE reaction
aspartate leaves mitochondria via glutamate-aspartate antiporter

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32
Q

What types of reactions are involved in the malate aspartate shuttle

A

redox
transamination

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33
Q

How many ATP molecules are produced by :
GTP/ATP
NADH
FADH2

A

GTP/ATP - 1 ATP
NADH - 3 ATP
FADH2 - 2 ATP

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34
Q

How many ATP molecules are produced by the TCA cycle

A

12 :
oxidation of 1 acetyl coA molecule gives
3x NADH
1x FADH2
1x GTP

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35
Q

Fatty acid metabolism

A

1- converting fatty acids to acyl CoA
2- transporting Acyl CoA from outer mitochondrial membrane into matrix (Carnitine shuttle)
3- actual Beta Oxidation Cycle

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36
Q

Beta-oxidation produces

A

> 50% bodys energy
Predominates in time of fasting (uses fat stores instead of carbs)

37
Q

Stage 1 of Fatty acid metabolism

A

converting fatty acid into fatty acyl CoA (using fatty acyl-CoA synthetase)
- requires 2 ATP
- occurs on outer membrane of mitochondria

38
Q

Stage 2 of fatty acid metabolism

A

CoA and carnitine both carry acyl group at different points

39
Q

Primary Carnitine Deficiency

A

Autosomal recessive disorder
- mutations in SLC22A5 which encodes carnitine transporter, so no CoA transported into matrix

40
Q

Stage 3 of fatty acid metabolism

A

Beta Oxidation - in mitochondria
one cycle :
Acyl CoA –> Acyl CoA SHORTER 2C + Acetyl CoA (2C)

41
Q

Steps of beta oxidation (4)

A

oxidation
hydrolysis
oxidation
thiolysis

42
Q

Why does the glycerol phosphate shuttle produce less ATP in the process of oxidative phosphorylation compared to the malate-aspartate shuttle

A

Electrons passed from cytoplasmic NADH to mitochondrial FADH2 which enter electron transport chain later leading to fewer H+ pumped and less ATP produced

43
Q

Example of Beta oxidation using palmitoyl CoA (16C)

A

palmitoyl CoA + 7FAD + 7NAD+ +7H20+ 7CoA —-> 8 acetyl CoA + 7FADH2 +7NADH

per cycle make - 1 acetyl CoA, 1 FAD2, 1NADH

44
Q

Thiolyis is

A

reaction of adding CoA to a compound

45
Q

When does Acetyl CoA from beta oxidation enter the TCA cycle

A

when carbohydrate metabolism = fat metabolism
Oxaloacetate needed for Acetyl CoA entry

46
Q

What happens to acetyl CoA when fat metabolism predominates (during fasting)

A

acetyl CoA forms ketone bodies

47
Q

3 examples of Ketone bodies

A

Acetoacetate
D-3-hydroxybutyrate
Acetone

48
Q

Why is there different enzymes feeding fatty acyl CoA into the beta oxidation cycle

A

depends on the length of the acyl CoA

49
Q

4 enzymes feeding fatty acyl CoA into B oxidation cycle

A

(<6C) short chain
(6-12) medium chain
(13-21) long chain 3-hydroxy
(>22) very long chain
acyl-CoA enzyme A dehydrogenase

50
Q

Medium chain acyl-coenzyme A dehydrogenase deficiency MCADD

A

autosomal recessive - predominantly in caucasians
1 in 10,000 live births in uk
If undiagnosed - fatal : accounts for 1 in 100 deaths from SIDS

51
Q

Precautions for patients with MCADD

A

never go without food for longer than 10-12h
adhere to high carbohydrate diet

patients with illness resulting in appetite loss or sever vomiting may need IV. glucose to make sure body isn’t solely dependent on fatty acids to make energy

52
Q

Two enzymes involved in fatty acid synthesis

A

Acetyl CoA Carboxylase
Fatty acid synthase

53
Q

What are fatty acids formed by
(process of lipogenesis)

A
  1. decarboxylative condensation reactions involving acetyl-CoA and malonyl-CoA
  2. following each round of elongation, fatty acid undergoes reduction and dehydration by dehydratase (DH) and enol reductase (ER) activity
  3. growing fatty acyl group is linked to an acyl carrier protein (ACP)
54
Q

Carriers in Beta oxidation

A

CoA

55
Q

Carriers in lipolysis

A

ACP (acyl carrier proteins)

56
Q

Reducing power in Beta oxidation

A

FAD/NAD+

57
Q

Reducing power in lipolysis

A

NADPH

58
Q

Location of Beta oxidation

A

mitochondrial matrix

59
Q

Location of lipolysis

A

Cytoplasm

60
Q

Oxidative phosphorylation

A

Electron transport chain
composed of :
four complexes
two mobile carriers - act as electron carriers

61
Q

Four complexes of ETC

A

Complex I - NADH dehydrogenase
Complex II - succinate dehydrogenase
Complex III - Q-cytochrome C oxidoreductase
Complex IV - cytochrome c oxidase

62
Q

Two mobile carriers in ETC

A

ubiquinone (co-enzyme Q)
cytochrome C

63
Q

What happens in the ETC

A

As electrons move between complexes, they release enough energy to transport protons from the matrix to the intermembrane space

64
Q

Two subunits of ATP synthase

A

f0 - membrane bound
f1 - matrix

65
Q

Formation of ATP by ATP synthase

A
  1. flow of H+ back into matrix
  2. generates mechanical rotation in the F0 subunit
  3. Causes conformational change in F1 subunit and forms ATP from ADP and phosphate
66
Q

When is complex I bypassed

A

electrons donated by other FADH2 molecules (generated in glycerol phosphate shuttle and B-oxidation) bypass complex 1

fewer protons generated so fewer ATP molecules generated

67
Q

most common cause of a failiure of oxidative phosphorylation

A

lack of oxygen e.g hypoxia (diminished), anoxia (total)

neurons - few minutes
muscle - few hours

68
Q

Metabolic poisons (5)

A

Rotenone - Inhibits Complex I (Ox. phos. can still occur)
Malonate - competitive inhibitor of complex II
N3- / CN- - binds to haem group in complex IV, blocking electron flow
DNP
Oligomycin - inhibits ATP synthase by blocking proton channel

69
Q

How does DNP work as a metabolic poison

A

provides alternative channel for H+ to travel through
Uncouples electron transport from ATP synth
Energy released as heat instead of for ATP
(similar mechanism in shivering thermogenesis)

70
Q

Hamartoma

A

localised benign overgrowths of one or more mature cell types
e.g in the lung

71
Q

Where is Acyl CoA generated

A

On outer mitochondrial membrane

72
Q

How does Acyl-CoA enter the mitochondrial matrix

A

Coupled to carnitine to form acyl carnitine
Translocase moves acyl carnitine and carnitine to and from matrix respectively.
Allowing B oxidation of fatty acids

73
Q

A child is diagnosed with carnitine deficiency. How might this condition lead to hypoglycaemia

A

Acyl CoA entry into mitochondria is impaired, reducing ATP production from fatty acid metabolism

74
Q

Lipoprotiens are

A

molecules made of a phospholipid and apoprotein exterior, carrying cholesterol esters and lipids on the interior

75
Q

Lipoproteins travel in

A

the bloodstream

76
Q

Cholesterol is carried as an ester because

A

the molecule becomes more hydrophobic and hence can be more tightly packed

77
Q

Types of lipoproteins (listed by incr. density)

A

Very low density lipoproteins VLDL
Intermediate density lipoproteins IDL
Low density lipoprotein LDL
High density lipoprotein HDL

78
Q

What determines lipoprotein density

A

Level of lipid content; fewer lipids means higher density

79
Q

2 most important lipoproteins

A

LDL and HDL

80
Q

HDL is known as

A

Good cholesterol
as it carries lipids and cholesterol away from peripheral tissues and into liver for use or disposal

81
Q

LDL is known as

A

Bad cholesterol
as it carries lipids and cholesterol into peripheral tissues.

82
Q

What can high levels of LDLs lead to

A

atherosclerosis

83
Q

6 factors leading to higher LDL levels

A

obesity
diabetes
smoking
age
sedentary lifestyle
poor diet

84
Q

Which shuttle (transporter of electrons) from cytoplasmic NADH into mitochondria produce a lower net ATP production? why?

A

Glycerol phosphate: e- passed from cytoplasmic NADH to mitochondrial FADH2
FADH2 donates e- directly to second e- transporter in ox. phos.
skipping first transporter in ETC
fewer H+ pumped so less ATP produced

85
Q

Non-shivering thermogenesis is the bodys response to temperature drop. How does this mechanism lead to an incr. in body temp.?

A

Uncoupling of oxidative phosphorylation dissipates proton gradient (allowing H+ to bypass ATP synthase channel), energy dissipated as heat

UCP1

86
Q

Upon accepting electrons, which complex does not pump protons from the matrix to intermembrane space

A

Complex II
succinate dehydrogenase
directly participates in ETC by transferring electrons to ubiquinone

87
Q

A redox couple with a positive E0 is more likely to

A

Act as an oxidising agent and accept electrons
- consistent with tendency to undergo reduction

88
Q

Effective treatment for primary carnitine deficiency

A

Carnitine supplements
increase overall availability of carnitine, essential for transport of fatty acids into mitochondria to produce ATP

POM 2: Molecular biology of the cell (9 decks)

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