Carbohydrate respiration Flashcards

1
Q

What are the three ways that we can process energy?

A

Heterotrophy- when an organism ingests or absorbs organic carbon to produce energy and synthesis compounds to maintain life
Autotrophy- When complex organic compounds are produced from simple substrates using light or inorganic chemical reactions
Phototrophy- photon capture to acquire energy- energy from light to carry out cellular metabolic processes

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2
Q

What are monosaccharides?

A

Simple sugars containing 3-7 carbons and an aldehyde or ketone functional group, e.g. glucose, ribose, galactose

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3
Q

What are Disaccharides?

A

A class of sugars whose molecules control two monosaccharides residues e.g. sucrose

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4
Q

What are oligosaccharides?

A

a carbohydrate whose molecules are composed of a relatively small number of monosaccharide units

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5
Q

Polysaccharides

A

High Mr polymers of many monosaccharides e.g. glycogen, starch, cellulose

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6
Q

What type of bond join two monosaccharides?

A

Glycosidic

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7
Q

What is the most common building block of polysaccharides?

A

D-glucose

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8
Q

What are the names of polysaccharides composed of single and many types of building blocks?

A

Homopolymers

Heteropolymers

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9
Q

What is the Mr of cellulose?

A

50,000

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10
Q

What is cellulose?

A

It is an unbranched polymer of glucose molecules connected by B1-4 links.

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11
Q

What is the structure of cellulose?

A
  • The B configuration allows cellulose to from very long straight chains.
  • Fibrils are formed by parallel chains that interacts with one another through hydrogen bonds
  • Because of β-1,4 links, alternating residues flipped through 180° relative to each other
  • H-bonds stabilise this, giving a linear secondary structure
  • Polymer chains have a high affinity for each other and form parallel bundles
  • The straight chain formed by β linkages is optimal for the construction of fibers having a high tensile strength
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12
Q

What is the function of cellulose?

A

Structural polymer

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13
Q

What are the main polysaccharides used in the storage of chemical energy?

A
  • Starch (plants)

- Glycogen (animals)

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14
Q

What is the structure of starch and glycogen?

A

-Both starch and glycogen are homopolymers of α-1-4 linked glucose with occasional α-1-6 branch points
-The α-1,4 linkages in glycogen and starch produce a very different molecular architecture from that of cellulose - the resulting open helix is well suited to forming an accessible store of sugar
• Glycogen has chains of 8-12 units long each with branches every 8-10 units, 2 branches per chain
• Starch has branched and unbranched forms. The branched forms have chains of 20-25 units with branches every 12-25 units
• Starch has longer chains than glycogen but fewer ends

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15
Q

Where is glycogen stored?

A

Glycogen is found in the cytosol as dense granules which contain glycogen and the enzymes involved in both its synthesis and mobilization

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16
Q

How do glycosidic bonds determine polysaccharide structure?

A

Beta linkages have bonds between groups above and below the ring -> straight chain
-a linkages have bonds between groups on one side of the ring -> chain curves

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17
Q

What causes a hollow helix instead of a straight chain?

A

The a1-4 linkages

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18
Q

Why is branching important in glycogen?

A

• Branched structure gives lots of non-reducing ends for fast breakdown and synthesis

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19
Q

What polysaccharides are used for recognition and signalling?

A

-Chondroitin sulfate, heparin, hyaluronate

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20
Q

Where are glycosaminoglycans found and is its function?

A

It is present on the animal cell surface and in the extracellular matrix.
They are involved in a variety of extracellular and intracellular functions

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21
Q

What are glycosaminoglycans made of?

A

-Disaccharide repeating units containing a derivative of an amino sugar, either glucosamine or galactosamine; at least one of the sugars in the repeating unit has a negatively charged carboxylate or sulfate group.

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22
Q

What are glycosaminoglycans attached too and what does this form?
What are their functions?

A

-Glycosaminoglycans are usually attached to proteins to form proteoglycans
-Proteoglycans function as lubricants and structural components in connective
tissue, mediate adhesion of cells to the extracellular matrix, and bind factors that stimulate cell proliferaiton
-Heparin contains the highest net negative charge of the disaccharides and acts as a natural anticoagulant substance

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23
Q

Where is glycogen made and broken down?

A

The liver and muscle

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24
Q

What are the biosynthesis and catabolic pathways of glycogen?

A

Synthesis (glycogenesis:
Glycogen +UDP-glucose –> glycogen (n+1) +UDP )

Degradation (glycogenolysis):
Glycogen +Pi -> Glycogen (n+1) + glucose 1- phosphate

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25
Q

What two enzymes convert glycogen to G1P?

A

debranching enzyme and glycogen phosphorylase

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26
Q

What enzyme converts G1P to G6P?

A

Phosphoglucomutase

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27
Q

What enzymes convert G1P too UDP-glucose? (glycogen synthesis)

A

UDP glucose pyrophosphorylase

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28
Q

What converts UDP-glucose to glycogen? (glycogen synthesis)

A

Glycogen synthase removed the UDP and branching enzyme

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29
Q

What does glycogen branching enzyme do?

A

Transfers glucose units. It transerd a 7 glucose unit from the end of a chain to a C6-OH group of a glucose residue on the same or another glycogen chain. Each transferred segment must come from a chain of at least 11 units; the new brach must be at least 4 units away from any other branch point

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30
Q

What does deficiency of glycogen branching enzyme cause? and what are the disease characteristics?

A

It causes glycogen storage disease type IV, a rare autosomal recessive disorder of the glycogen synthesis. This disease is characterized by the accumulation of amylopectin like polysaccharides in almost all tissues.

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31
Q

What are the 4 steps to glycogen degradation?

A

1- phosphorylase
2-glycogen debranching enzyme
3-Phosphorylase
4-phosphoglucose mutase

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32
Q

what is particular about step 2 of degradation?

A

-As glycogen phosphorylase will only cleave glucose units more than 5 from a branch point, branch points need to be removed
-Glycogen debranching enzyme is an α(1,4) transglycosidase which transfers an α(1,4) trisaccharide unit from a limit
branch to the non-reducing end of a new branch.

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33
Q

What is particular about step 3 of degradation?

A
  • The remaining glucose unit can be hydrolysed by the same enzyme to yield glucose
  • Phosphorylase is quick; debranching slow
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34
Q

What is particular about step 4 of degradation?

A

Phosphorylase generates G1P units which are converted to G6P by this enzyme
• Major difference between this and the phosphoglycerate mutase of glycolysis is that this enzyme uses a Ser-P rather than a His-P

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35
Q

What are the fates of glycogen degradation products?

A

Glucose 6-phosphate is either converted to fructose 6 phosphate and undergoes glycolysis to produce ATP, CO2 and H2O in the muscle. Ot is might be converted to glucose and exported to the blood in the liver

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36
Q

How is glycogen breakdown controlled?

A

By active and inactive forms of phosphorylase

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37
Q

What is Pompes disease?

A

A defect in acid α glucosidase in lysosomes, which acts on α1-4 glycosidic bonds, i.e. blocks conversion of glycogen à glucose
• Glycogen builds up in lysosomes, resulting in low [glucose]
• Causes progressive muscle weakness, and trouble breathing

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38
Q

What is Coris disease?

A
  • An autosomal recessive metabolic disorder and inborn error of metabolism
  • A deficiency in debranching enzyme resulting in excess glycogen and low glucose
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39
Q

What is McArdles disease?

A

Deficiency in glycogen phosphorylase in skeletal muscle (myophosphorylase)
• The onset of this disease is usually noticed in childhood
• Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps
• Low glycogen levels à low glucose-1-P

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40
Q

What is the importance of glycogen metabolism?

A

-Regulates blood glucose concentration
• Provides a reservoir of glucose for muscle activity
• Illustrates an important concept:
Synthesis and degradation of biopolymers involve different pathways
• Mechanism of hormonal regulation of glycogen metabolism is characteristic of such processes

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41
Q

What hormones regulate glycogen synthesis and degradation?

A

adrenaline and insulin

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42
Q

What regulates glucose uptake by cells?

A
  • glucose outside&raquo_space; glucose inside
  • Glucose requires a transporter protein
  • Different transporters in different tissues, named GLUT-1 to GLUT-5
  • Reversible exchange - diffusion direction dependent on concentration gradient
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43
Q

What is GLUT 4 regulated by?

A

Insulin

• Insulin increases the number of GLUT-4 molecules in the membrane = increased glucose uptake

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44
Q

What is the first step of glucose metabolism?

A

Glucose–> glucose 6 phosphate catalysed by hexokinase

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45
Q

What is the first step of glucose metabolism? and what is its function?

A

Glucose–> glucose 6 phosphate catalysed by hexokinase
Iis function is too maintain the conc. in the cell as this steps turns it into something that cannot move out of the cell and therefore is used in metabolism.

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46
Q

What are the characteristics of the first step of glucose metabolism?

A
  • Uses 1 ATP to phosphorylate the carbonyl group on carbon 6
  • Essentially an irreversible reaction,with a high affinity for glucose
  • Hexokinase is negatively regulated (inhibited by G6P)
  • Helps control which tissues have access to glucose
  • Commits the glucose to use by this cell in peripheral tissues, but not to a specific use
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47
Q

What is the overview of glycolysis?

A

•Splits a 6C sugar into 2 x 3C sugars (glycolysis)
– needs a carbonyl group at carbon 2 (i.e. fructose)

• Oxidises the 3C sugars to pyruvate
– needs an oxidising agent (NAD+)
– needs an electron sink -either O2 (aerobically) or lactate (anaerobically)
• Captures the energy by converting ADP to ATP
– needs to add phosphate to the sugars

  • Requires 10 enzymes, 11 compounds needed for glycolysis, starting from glucose, all located in the cytosol
  • We split one glucose into 2x pyruvate over 10 steps
  • Mg is a cofactor meaning that if there is not enough this process stops
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48
Q

where does the first step of glucose metabolism occur?

A

In the cytosol and therefore there is no compartmentalisation

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49
Q

What are the three main control point?

A

1- hexokinase glucose +ATP -> glucose 6 phosphate +ADP
2-Phosphofructokinase-1-fructose-6-phosphate +ATP -> fructose 1-6-bisphosphate
3-Pyruvate kinase phosphoenolpyruvate +ADP -> pyruvate +ATP

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50
Q

What are the other 2 sugars funnelled into glycolysis?

A

Galactose
-Galactokinase converts galactose to galactose-1-phosphate then to G6P

Fructose
-Fructokinase converts fructose to fructose-1-phosphate (liver)
or
hexokinase converts fructose to fructose-6-phosphate
Fructose bypasses the first control point and therefore is useful in sport

51
Q

What is the net reaction of glucose metabolism?

A

Glucose + 2Pi + 2ADP+ 2NAD+ —-> 2 pyruvate + 2ATP + 2NADH + 2H+ + 2H2O

52
Q

What are the net yields of glucose and glycogen after glycosis?

A
Glucose = 2ATP starting from glucose 
GLycogen= 3 ATP as it yields G-6-P from inorganic phosphate
53
Q

What are the three fates of pyruvate?

A

Amino acids, acetyl-CoA and lactate

54
Q

Why do we have lactate production?

A

To regenerate NAD+

55
Q

whats the overall lactate reaction?

A

pyruvate + NADH —> Lactate + NAD+

56
Q

What enzyme catalyses lactate production?

A

lactate dehydrogenase

57
Q

What are the two isoforms of lactate dehydrogenase?

A

-M and H.
-skeletal muscle contains M4 and heart H4.
H4 favours the reverse reaction to help prevent the buildup of lactate in the heart muscle whereas in the muscle you need energy and the buildup of lactate is less important

58
Q

What is the reaction to convert pyruvate to alanine?

A

pyruvate + amino acid (e.g. glutamate) –> alanine + a-ketoglutarate

59
Q

what enzyme catalyses the reaction of pyruvate to acetyl coenzyme A?

A

Pyruvate dehydrogenase

60
Q

What is the overall reaction of pyruvate to acetyl coenzyme A?

A

pyruvate + NAD+ + HSCoA —> acetyl coenzyme A+ NADH +CO2

61
Q

What are the general facts about acetyl coenzyme A creation?

A
  • Also known as the link reaction as it links glycolysis to the TCA cycle
  • It is catalysed by an enzyme complex in the mitochondria (PDH)
  • This is an irreversible, exergonic reaction: ΔG°‘ = -33.4kJ mol-1
62
Q

What is the structure of the pyruvate dehydrogenase complex?

A

• The reaction occurs in 4
steps, catalysed by 3 enzymes
• Two in the outer shell, 1 in the inner shell
• Bringing enzymes together like this makes the reaction faster,
allows control as I unit

63
Q

What functions does the link reaction serve in an organism?

A

•Provides Acetyl CoA
• Acetyl CoA cannot be converted back to glucose
• Hence, formation of Acetyl CoA commits the 2x3 carbon units from glucose to either
-oxidation to CO2 via the TCA, or
incorporation into lipids (therefore cannot use fats to directly generate glucose)

• This is a key decision point in carbohydrate metabolism and the activity of PDH is carefully controlled in the cell an important control point in exercise metabolism

64
Q

How much glucose is needed per day?

A

160g

65
Q

what is blood glucose levels maintained at?

A

5mM

66
Q

What is the definition of gluconeogenesis?

A

Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources e.g. pyruvate, lactate, amino acids, glycerol

67
Q

what is the overall reaction of gluconeogenesis

A

2 pyruvate +4ATP +2GTP +2NADH + 2H+ —> 1glucose +4ADP + 2GDP +6Pi +2NAD+

68
Q

What type of reaction is gluconeogenesis?

A

exergonic

-9KcalMol-1

69
Q

Where does the control of the glucose pathway come in?

A

1) Hexokinase is inhibited by Glucose-6-P

2) PFK is inhibited by ATP

70
Q

What enzyme converts glucose to G6P?

A

hexokinase

71
Q

What enzyme converts F6P to FBP?

A

PFK

72
Q

What enzyme converts PEP to pyruvate?

A

pyruvate kinase

73
Q

What enzyme converts pyruvate to PEP?

A

Pyruvate carboxylase +PEPCK

74
Q

What converts FBP to F6P?

A

FBPase

75
Q

What converts G6P to glucose?

A

Glucose– phosphatase

76
Q

What is PFK inhibited and activated by?

A
  • Activated ADP, AMP, FBP

- Inhibited by ATP

77
Q

What are the two multi organ cycles?

A

Cori and alanine cycles

78
Q

What does the cori cycle do?

A

Allows recovery of glucose after hard exercise

79
Q

What does the alanine cycle do?

A

moved NH3 groups to the liver

80
Q

Where does the TCA cycle occur?

A

in the mitochondrial matrix

81
Q

where does the ETC occur?

A

on the inner mitochondrial membrane

82
Q

what is the permeability of each mitochondrial membrane and what does this mean?

A

-Outer mitochondrial membrane is permeable to molecules of up to 1000Da
-The inner membrane is relatively impermeable and the impermeability of the inner membrane is essential for ATP synthesis, but means
that transporter proteins are required to move metabolites in and out of mitochondria

83
Q

Where is pyruvate converted to acetyl CoA?

A

the mitochondrial matrix

84
Q

What is the TCA overall reaction?

A

Acetyl CoA + 3NAD+ +FAD +GDP + Pi + H2O —> CaASH +3(NADH+H+) + FADH2 +GTP +2CO2

85
Q

What is the concept of chemiosmosis?

A

-Electrons from NADH and FADH made by the TCA cycle are transferred in steps to molecular oxygen to produce water
-The energy released by these reactions is conserved in the form of a proton gradient
that is used to drive synthesis of ATP
protons are pumped across the membrane as electrons flow throguh the respiratory chain.
- A proton gradient links the ETC and ATP synthesis. THe intermembrane space is acidic and positive compared to the matrix
-When there is a conc gradient it creates a potential gradient meaning that H+ pass through ATP synthase and creates energy,

86
Q

What is the difference between the intermembrane space and the matrix?

A

The intermembrane space is acidic and positive compared to the matrix

87
Q

What is the energy available from transfer of electrons from NADH to O2

A

-52.6 kcal mol-1

88
Q

What is the energy available from transfer of electrons from FADH2 to O2

A

-46 kcal mol-1

89
Q

What energy is required to make ATP?

A

+7.3 kcal mol-1

90
Q

What complexes are involved in the respiratory chain?

A

-Complex I (NADH Dehydrogenase)
-Complex II Succinate dehydrogenase)
-Ubiquinone
-Complex III (Cytochrome bc1)
-Cytochrome c
Complex IV (Cytochrome oxidase)

91
Q

What is a redox potential?

A
  • The redox potential (Eo’) of a compound is a measure of its tendency to donate electrons to another compound, i.e. to reduce it. The more negative the redox potential, the better the reducing ability.
  • Compounds can accept electrons from other compounds with more negative redox potentials and can donate electrons to those with more positive redox potentials.
92
Q

What is the progressive redox potential of the proteins in the ETC?

A
  • Electron transport chain components are organised in the inner membrane such that their individual redox potentials become successively more positive.
  • This allows electrons to be transferred along the chain.
  • Oxygen, with a large positive redox potential, is the final acceptor of the electrons.
93
Q

What happens at NADH dehydrogenase?

A
  • Two electrons (carried within a hydride ion H-) are transferred from NADH to Complex I (NADH dehydrogenase). They are accompanied by a proton from the matrix.
  • NADH can donate electrons to the electron transport chain because its redox potential is more negative than that of Complex I.
  • Energy released as the electrons move from NADH through Complex I is used to pump four protons from the matrix to the intermembrane space
94
Q

What happens at ubiquinone?

A

The electrons are transferred on to ubiquinone from NADH dehydrogenase. Two protons accompany the electrons and react to form QH2

95
Q

What happens at complex III?

A
  • Electrons are transferred from QH2 to Complex III (cytochrome bc1).
  • Energy released as electrons move through Complex III is sufficient to pump four protons into the intermembrane space. Two protons are taken up from the matrix.
96
Q

What happens at cytochrome C and complex IV?

A
  • Electrons are transferred from Complex III (cytochrome bc1) to cytochrome c, which then carries the electrons on to Complex IV (cytochrome oxidase).
  • The electrons donated by cytochrome c are used by Complex IV to reduce molecular oxygen, which then reacts with protons from the matrix to form water.
  • Energy released when electrons pass through Complex IV is sufficient to pump two additional protons across the membrane.
97
Q

What is the first step of FADH2 donation?

A
  • FADH2 cannot donate electrons to Complex I, which has a more negative redox potential, but its two electrons are fed directly to ubiquinone which has a more positive redox potential. They are accompanied by two protons, to produce QH2
  • There is insufficient energy released for protons to be pumped across the membrane when electrons are transferred from FADH2 to ubiquinone.
98
Q

What enzymes create FADH2?

A

Succinate dehydrogenase
Glycerol-3-phosphate dehydrogenase
Acyl-CoA dehydrogenase

99
Q

How is complex II involved in the ETC?

A

It is the enzyme succinate dehydrogenase and therefore is used to convert FAD + succinate to FADH2 + fumarate

100
Q

What happens at complex III in FADH2 donation?

A
  • Electrons are transferred from QH2 to Complex III (cytochrome bc1).
  • Energy released as electrons move through Complex III is sufficient to pump four protons into the intermembrane space. Two protons are taken up from the matrix.
101
Q

What happens at complex IV in FADH donation?

A
  • Electrons are transferred from Complex III (cytochrome bc1) to cytochrome c, which then carries the electrons on to Complex IV (cytochrome oxidase).
  • The electrons donated by cytochrome c are used by Complex IV to reduce molecular oxygen, which then reacts with protons from the matrix to form water.
  • Energy released when electrons pass through Complex IV is sufficient to pump two additional protons across the membrane.
102
Q

How many protons are pumped per NADH oxidized?

A

10

103
Q

How many protons are pumped per FADH2 oxidized?

A

6

104
Q

How does the synthesis of ATP work?

A
  • There is a higher concentration of protons in the inter-membrane space than in the mitochondrial matrix – they have been pumped across the membrane by Complexes I, III and IV of the electron transport chain.
  • Protons travel down their concentration gradient back into the matrix through the ATPase.
  • For every three protons passing through the ATPase, one molecule of ATP is formed.
105
Q

What occurs alongside the synthesis of ATP?

A
  • The ATPase needs ADP and Pi as substrates. These enter the mitochondrial matrix via transporters.
  • The adenine nucleotide translocase is driven by the charge difference across the inner membrane as a result of the proton gradient, and exchanges ADP3- for ATP4-.
  • The phosphate translocase is also driven by the proton gradient and is a symport for Pi and H+.
106
Q

What is ATP synthesis coupled with?

A

ATP synthesis is coupled to the reduction of oxygen.

107
Q

What is the structure of ATPsynthase?

A

-F1 is composed of 3 a and 3 b subunits.
-b is the catalytic subunit, a is regulatory
-g connects F1 to Fo
-Fo comprises a ring of hydrophobic
proteins that act as a H+ channel
-As protons flow through the Fo channel it rotates. This in turn drives rotation of the g subunit which drives conformational changes in a and b

108
Q

What are the steps of the mechanism of ATP synthesis?

A
  1. The T conformation has such a high affinity for ATP that bound ADP +Pi are converted to ATP.
  2. This ATP cannot be released until a conformational change driven by the rotation of the g subunit converts the T conformation to the O conformation
  3. ADP and Pi bind to the vacant O site. A further rotation converts O to L and L to T resulting in the synthesis of a second molecule of ATP
109
Q

How many protons are required per ATP synthesised?

A

4

110
Q

How much ATP can we make per molecule of FADH2 or NADH oxidised by the ETC?

A

NADH: 10 H+ pumped per NADH
ATP synthesis: 4H+ per ATP
10 ÷ 4 = 2.5 molecules of ATP per NADH

FADH2: 6 H+ pumped per FADH2
ATP synthesis: 4H+ per ATP
6 ÷ 4 = 1.5 molecules of ATP per FADH2

111
Q

How many molecules of ATP can be made from 1 molecule of glucose?

A

32

112
Q

What is complex I inhibited by?

A

rotenone

113
Q

What is complex IV inhibited by?

A

Cyanide and

Carbon monoxide

114
Q

What is complex III inhibited by?

A

Antimycin A

115
Q

What is ATP synthase inhibited by?

A

oligomycin

116
Q

What is ATP/ ADP carrier inhibited by?

A

carboxyatractyloside

117
Q

What are uncouplers?

A

Uncouplers are agents that increase the
permeability of the mitochondrial inner membrane to protons.

This prevents the build up of a H+ gradient and therefore inhibits ATP synthesis
indirectly. Electron transport can continue at its maximum rate as long as substrate (e.g NADH)
and oxygen are available.

118
Q

What is the malate- aspartate shuttle used for?

A

-The malate-aspartate shuttle for transporting reducing equivalents
-Important for oxidising cytosolically generated NADH as NAD+ and NADH
cannot cross the mitochondrial inner membrane

119
Q

What catalyses the transformation of malate to oxaloacetate?

A

Malate dehydrogenase

120
Q

What catalyses the transformation of oxaloacetate to aspartate?

A

Aspartate amino transferase

121
Q

What catalyses the transformation of aspartate to oxaloacetate ?

A

Aspartate amino transferase

122
Q

What catalyses the transformation of oxaloacetate to malate?

A

Malate dehydrogenase

123
Q

What is the topping up cycle?

A

-If intermediates that are removed for biosynthesis are not replenished the cycle
will stop
-Note that all carbon that enters as the acetyl group is oxidised to CO2, so
Simply putting in more acetyl CoA is no help
-Pyruvate carboxylase provides a means of replenishing oxaloacetate

124
Q

What are the controls of the TCA cycle?

A

-The products of the cycle,ATP and NADH inhibit it by activating a protein kinase that phosphorylates and inhibits PDH
-There is also regulation of PDH activity by hormones, e.g. Insulin stimulates PDH dephosphorylation and therefore activation
-ATP, acetyl CoA and NADH inhibit Pyruvate dehydrogenase
-ATP and NADH inhibit whilst ADP simulates a ketoglutarate dehydrogenase
-ATP, succinyl CoA and NADH inhibit Succinyl CoA
synthetase