Session 2 Flashcards
(121 cards)
1
Q
What is the main product of glycolysis?
A
Pyruvate
2
Q
What happens to the pyruvate produced in glycolysis?
A
Enters the link reaction where it is converted to acetyl CoA and carbon dioxide is given off
3
Q
How many carbons are in a molecule of pyruvate? How many carbons are in a molecule of acetyl CoA?
A
3
2
4
Q
Where does the conversion of pyruvate to acetyl CoA take place in the cell? What enzyme catalyses this reaction?
A
Mitochondrial matrix
Pyruvate dehydrogenase
5
Q
What is the structure of Pyruvate dehydrogenase?
A
Complex made up of 5 enzymes
6
Q
Give examples of cofactors required for the different enzymes that make up pyruvate dehydrogenase. What are these derived from? What are the clinical implications of this?
A
FAD, lipolic acid
B vitamins
Reactions are sensitive to vitamin B1 deficiency
7
Q
Is the link reaction reversible or irreversible? Why?
A
Irreversible
Involves the loss of carbon dioxide
8
Q
What reaction takes place in the link reaction?
A
Pyruvate + CoA + NAD+ ——> Acetyl CoA + CO2 + NADH + H+
9
Q
PDH deficiency can result in…
A
Lactic acidosis
10
Q
High energy substrates will cause PDH to ___________ its activated
Low energy substrates will cause PDH to __________ its activity
A
Lower
Increase
11
Q
Give examples of molecules that act as activators for PDH
How do these molecules have an effect on PDH
A
Pyruvate
NAD+
ADP
Insulin
Through dephosphorylation
12
Q
Give examples of molecules that act as inhibitors for PDH
How do these molecules have an effect on the PDH
A
Acetyl CoA
NADH
ATP
Citrate
Through phosphorylation
13
Q
Where does the TCA cycle (Krebs cycle) take place in a cell?
A
Mitochondrial matrix
14
Q
How many molecules of carbon dioxide are released per acetyl CoA entering the TCA cycle?
A
2
15
Q
Does the TCA cycle involve oxidative or reductive reactions?
A
Oxidative
Requires NAD+ and FAD
16
Q
Is energy produced in the TCA cycle? If so, in which forms?
A
Yes
ATP & GTP
17
Q
The TCA cycle is important for producing precursors for ____________
A
Biosynthesis
18
Q
Can the TCA cycle function in the absence of oxygen?
A
No
19
Q
Per glucose entering glycolysis TCA produces…
A
6 NADH
2 FADH2
2 GTP
4 CO2
20
Q
Acetyl CoA joins with which 4 carbon compound to form which 6 carbon compound in the TCA cycle?
A
Oxaloacetate
Citrate
21
Q
How is the TCA cycle regulated?
A
By energy availability (e.g. High energy switches TCA cycle down)
By enzymes acting on the irreversible steps that involve the release of carbon dioxide
22
Q
Which enzyme regulates the first irreversible step of the TCA cycle? What reaction does it catalyse?
A
Isocitrate dehydrogenase
Iscocitrate —> a-ketoglutarate
23
Q
Which enzyme catalyses the second irreversible reaction of the TCA cycle? What reaction does it catalyse?
A
A-ketoglutarate dehydrogenase
A-ketoglutarate —> succinyl-CoA
24
Q
TCA supplies precursors for biosynthetic processes , give some examples.
A
Citrate can be used to form fatty acids
Malate can be used to form amino acids
25
At the end of the TCA cycle all C-C and C--H bonds have been broken. What has happened to all the C atoms and H atoms?
All the C atoms have been oxidised to CO2
| All the H atoms have been transferred to NAD+ and FAD
26
The high energy electrons in NADH and FADH2 are transferred to __________ with the release of large amounts of __________ which is used to drive _________ _________
Oxygen
Energy
ATP synthesis
27
What is stage 4 of carbohydrate metabolism? Where does this take place in the cell?
Electron transport and ATP synthesis
Inner mitochondrial membrane
28
What happens to the NADH/FADH2 in stage 4 of carbohydrate metabolism?
They are re-oxidised back to NAD+ and FAD
29
What happens to oxygen in stage 4 of carbohydrate metabolism?
Gains electrons and is reduced to water
30
A concentration gradient of which ions is set up across the inner mitochondrial membrane during stage 4 of carbohydrate metabolism? What is another term for this concentration/electrical gradient created?
H+ ions
Proton motive force
31
Describe the permeabilities of the inner and outer mitochondrial membranes
Outer - relatively permeable
| Inner - highly impermeable
32
How are hydrogen ions pumped into the intermembrane space?
Electrons are released in the oxidation of NADH (and FADH2)
Electrons are passes on to proton translocation complexes in the inner mitochondrial membrane
Electrons lose energy as they pass through the PTC, energy used to drive H+ ions through the PTC into the inter-membrane space
H+ ion gradient created
33
How many PTCs do the electrons released in the oxidation of NADH pass through?
3
34
How many PTCs do the electrons produced in the oxidation of FADH2 pass through? Why is this number different than for NADH?
2
Electrons are already at lower energy in FADH2
35
How many H+ ions are pumped through in the oxidation of one molecule of NADH? How many H+ ions are pumped through in the oxidation of one molecule of FADH2?
6
4
36
What happens at the end of the electron transport chain to produce water?
2 electrons are picked up by atomic oxygen and 2 hydrogen ions to produce water (reduction reaction)
37
What happens to the hydrogen ions in the intermembrane space to produce ATP?
Pass through ATP synthase in the inner mitochondrial membrane back through to the matrix driving ATP synthesis
38
Can ATP synthase also work in the reverse direction?
Yes as ATPase
39
Which is the only route by which hydrogen ions can pass back through the inner mitochondrial membrane? Why is this?
via ATP synthase
Inner mitochondrial membrane is impermeable
40
How many moles of ATP are produced in the oxidation of 2 moles of NADH? How many moles of ATP are produced in the oxidation of 2 moles of FADH2?
5
3
41
Both oxidative phosphorylation and the electron transport chain are regulated by...
Give an example of how this works
Mitochondrial [ATP]
```
High ATP = Low ADP
No substrate for ATP synthesis
Inward flow of H+ stops
Increased H+ ion concentration in intermembrane space
Less H+ ions pumped
Electron transport chain stopped
```
42
Give an example of an inhibitor that blocks electron transport. What consequence will this have on oxidative phosphorylation?
CO, CN-
No PMF, no oxidative phosphorylation
43
How does cyanide (CN-) specifically work as an inhibitor of the electron transport chain?
Prevents acceptance of electrons by oxygen
44
Give an example of an uncoupler of oxidative phosphorylation
Dinitrophenol
Dinitrocresol
Fatty acids
45
How do uncouplers of oxidative phosphorylation work?
Increase the permeability of the inner mitochondrial membrane to H+ ions
Protein gradient dissipated through uncoupling molecule rather than ATP synthase
Reduced proton motive force
Less ATP synthesis
46
What are ox/phos disease caused by? What effect can they have on carbohydrate metabolism?
Genetic defects in proteins encoded by mtDNA (e.g. Subunits of PTCs and ATP synthase)
Reduction in electron transport and ATP synthesis
47
Efficiency of the electron transport chain/oxidative phosphorylation depends on tightness of coupling.
In which form is energy commonly lost in these processes?
In brown adipose tissue, how is this coupling controlled?
What does this allow?
Heat
By fatty acids acting as uncouplers
Allowing extra heat generation
48
Where is brown adipose tissue commonly found? What is its function?
In newborn infants
To maintain heat, particularly around vital organs
49
What uncoupling protein is found in brown adipose tissue?
Thermogenin (UCP1)
50
How does thermogenin (UCP1) work to produce extra heat in response to the cold?
Noradrenaline activates lipase which releases fatty acids from TAGs
Fatty acid oxidation produces NADH/FADH2 and begins electron transport
Fatty acids activate UCP1
UCP1 (rather than ATP synthase) transports H+ back into the mitochondria
Energy of PMF released as extra heat
51
How many moles of ATP are produced per mole of glucose that enters glycolysis (in all stages of carbohydrate metabolism)?
32
52
Does oxidative phosphorylation or substrate level phosphorylation provide most of the ATP required in cells?
Oxidative phosphorylation
53
Can oxidative phosphorylation or substrate level phosphorylation occur in the absence of oxygen?
Oxidative - no
Substrate level - to a limited extent
54
Are lipids generally soluble or insoluble?
Insoluble
55
Lipids consist of which 3 elements only?
Phospholipids contain which 2 additional elements?
C, H and O
P and N
56
Do lipids release more or less energy than carbohydrates when oxidised? Why?
More
More reduced than carbohydrates, so require more oxygen for complete oxidation
57
What are the three classes of lipids?
Fatty acid derivatives
Hydroxy-methyl-glutaric acid derivatives
Vitamins
58
Name some molecules that fit into the fatty acid derivative class of lipids (4)
Fatty acids
Triacylgylcerols
Phospholipids
Eicosanoids
59
What is the function of fatty acids and triacylgylcerols?
Fuel molecule
Fuel storage and insulation
60
What are eicosanoids?
Local mediators
61
Name some molecules that fit into the hydroxy-methyl-glutamic acid derivative class of lipids (4)
Kentone bodies
Cholesterol
Cholesterol esters
Bile acids and salts
62
What are ketone bodies? How many carbon atoms do they contain?
Water soluble fuel molecules
4
63
What can cholesterol be used for? How many carbon atoms does cholesterol contain?
Membranes and steroid hormone synthesis
27
64
What are the functions of cholesterol esters and bile acids/salts? How many carbon atoms do bile acids/salts contain?
Cholesterol storage
Lipid digestion
24
65
Name the lipid soluble vitamins?
A, D, E and K
66
The difference in energy storage between a healthy and obese person will be shown in their increased levels of...
How are the levels of glycogen stores and muscle protein affected?
Triacylglycerols
Remain the same
67
What is the composition of a triacylglycerol? In which reaction type are they produced?
Glycerol backbone + 3 fatty acids
Esterification
68
Triglycerides are hydrophobic and therefore stored in _____________ form
Anhydrous
69
TAGs are stored in which tissues? In what circumstances are they utilised?
Adipose tissue
Prolonged exercise
Starvation
Pregnancy
70
Where are dietary TAGs initially broken down in the body? (stage 1 of metabolism) What happens here? What are the TAGs broken down to?
In the GI tract, extracellularly
Hydrolysed in small intestine by pancreatic lipases
Fatty acids and glycerol
71
Which enzymes hydrolyse TAGs in the small intestine?
Pancreatic lipases
72
How many carbons are there in a glycerol molecule?
3
73
What happens to the fatty acids and glycerol produced in the hydrolysis of dietary TAGs in the GI tract?
They are recombined in the small intestine and transported as TAG by chylomicrons. Then released into the circulation via lymphatics to adipose tissue.
74
TAGs can either be transported to ______________ tissues for...
OR
__________ tissue for...
Consumer
Fatty acid oxidation and energy production
Adipose tissue
Storage
75
Where in a cell does fatty acid oxidation take place? Where will fatty acids not be transported to in the body? (2)
Mitochondria
To cells without mitochondria (e.g. RBCs)
The brain - don't easily pass through the blood-brain barrier
76
TAGs in adipose tissue can be mobilised under ___________ control
Hormonal
77
How are fatty acids transported to consumer tissues once mobilised in adipose tissue?
Bound to albumin forming an FA-albumin complex
78
What hormones result in increased/decreased fat mobilisation?
Insulin - decreased
| Glucagon/Adrenaline - increased
79
What happens to TAGs in adipose tissue?
Undergo a constant cycle of breakdown and resynthesis
80
What does the resynthesis of TAGs in adipose tissue require? What will happen if there is not enough of this substance?
Constant supply of glucose
Results in fatty acids being released into the circulation as an alternative fuel (not resynthesised into TAG)
81
Fatty acids can be either saturated, unsaturated or amphipathic. What is meant by this?
Containing only single C-C bonds
Containing one or more C=C bonds
Containing hydrophilic and hydrophobic groups
82
Give an example of a polyunsaturated fatty acid that is essential and required in the diet? Why is it required from the diet?
Linolenic acid
Mammals cant introduce a double bond in fatty acids beyond C9
83
Where does stage 2 of fatty acid metabolism take place in target tissues?
Mitochondria
84
What happens to the fatty acids once they have been transported to consumer tissues?
Fatty acid is activated by linking to coenzyme A in the cytoplasm
85
How are activated fatty acids transporter across the inner mitochondrial membrane into the mitochondria?
Using a carnitine shuttle
86
What happens to the fatty acid once it has been transported into the mitochondria?
It cycles through a sequence of oxidative reactions with 2 carbons removed each cycle
87
Where does fatty acid activation take place? Which enzyme catalyses the activation of fatty acids?
Cytoplasm
Fatty acyl CoA synthase
88
What is the function of carnitine shuttles?
Transport activated fatty acids across the mitochondrial membrane
89
How are acyl-CoA (activated fatty acids) transported in carnitine shuttles?
There is an exchange of CoA for carnitine producing acyl carnitine
Acyl carnitine can be recognised and transported by the carnitine shuttle
Reverse reaction occurs in the matrix, reproducing acyl-CoA and the carnitine is recycled
90
Which enzymes catalyse the exchange of CoA for carnitine and then the reverse reaction?
CAT1
CAT2
91
The carnitine shuttle process is regulated therefore controlling the rate of...
This process is inhibited by...
Fatty acid oxidation
High energy levels - e.g. Levels of malonyl-CoA (biosynthetic intermediate)
92
Where does beta oxidation of fatty acids take place? Can it take place in the absence of oxygen?
Mitochondrial matrix
No
93
What happens in the beta oxidation of fatty acids? What molecules are produced/used - how does this result in the production of ATP?
A series of oxidative reactions where 2C are removed from the fatty acid each cycle
```
FADH2 and NADH are produced to be used in the electron transport chain
Acetyl CoA (2C) produced for use in the TCA cycle
```
Water and CoA are required
94
Are carbohydrates or fats a more high energy fuel?
Fats - fatty acid oxidation derives more energy
95
How is glycerol transported in the body and where is it metabolised?
Blood
Liver
96
Glycerol is converted during its metabolism into glycerol phosphate through the action of which enzyme?
Glycerol kinase
97
Glycerol is metabolised in the liver and is used for either...
Glycolysis
| Synthesis of TAGs
98
Acetyl-CoA is derived from which vitamins?
It is an important intermediate in both _________ and __________ pathways
What is the structure of acetyl-CoA
B vitamins
Anabolic and catabolic
CH3CO group linked to coenzyme A
99
Where are ketone bodies specifically synthesised? What are they?
Liver mitochondria
Water soluble fuel molecules
100
What are the 3 ketone bodies produced in the body?
Acetoacetate
Acetone
B-hydroxybutyrate
101
How is acetone produced?
Through the spontaneous breakdown of acetoacetate
102
Are ketone bodies hydrophobic or hydrophilic? How are they transported in the plasma?
Hydrophilic
Freely, without carrier molecules
103
What is the normal plasma ketone body concentration?
Less than 1 mM
104
What is the plasma ketone body range seen in starvation (physiological ketosis)?
2-10 mM
105
Ketone bodies are produced from...
How will the levels of ketone bodies in the plasma be affected in the case of reduced glucose levels?
Fatty acids ---> Acetyl CoA ---> Ketone bodies
Reduced glucose, will release fatty acids which and produce ketone bodies resulting in an increased concentration
106
What plasma concentration of ketone bodies can be seen in untreated type 1 diabetes (pathological ketosis)?
>10 mM
107
Which enzyme is inhibited by statins?
HMG-CoA reductase
108
Acetoacetate is produced from which molecule? Through the action of which enzyme?
HMG-CoA (from acetyl CoA)
HMG CoA lyase
109
Which enzyme catalyses the production of HMG-CoA from Acetyl CoA?
HMG-CoA synthase
110
How does a low glucose concentration resulting in increased production of ketone bodies?
Increased mobilisation of fatty acids
Oxidation of fatty acids producing NADH and acetyl CoA
Acetyl CoA can be used for the synthesis of ketone bodies
111
In states of starvation (low glucose), how is acetyl CoA used for the production of ketone bodies rather than in the TCA cycle?
Oxidation of fatty acids produces NADH - a high energy signal that inhibits the regulatory enzymes of the TCA cycle
112
What are the regulatory enzymes of the TCA cycle?
Isocitrate dehydrogenase
| A-ketoglutarate dehydrogenase
113
How are ketone bodies metabolised?
Transported in the blood from the liver to the muscles where they are converted to acetoacetate and fed into the TCA cycle for the resynthesis of acetyl CoA
114
Ketone body synthesis is regulated by...
The insulin/glucagon ration
115
Describe the regulation of ketone body synthesis in the fed state.
In the fed state, there is a high level of insulin - resulting in the inhibition of HMG-CoA lyase and the activation of HMG-CoA reductase resulting in cholesterol synthesis and less ketone body production
116
Describe the regulation of ketone body synthesis in starvation?
High levels of glucagon
HMG CoA lyase activated, HMG CoA reductase inhibited
Increased ketone body synthesis, rather than cholesterol synthesis
117
What happens in early starvation with regards to any remaining circulating glucose and ketone body production?
Ketone bodies begin to be produced
Any remaining circulating glucose conserved for use by the brain
118
How is the brain fuelled in late starvation when glucose levels are very low?
Protein in muscle begins to break down to amino acids
Amino acids used for gluconeogenesis
Glycogenolysis: glycogen ---> glucose
Glucose used in brain (rarely ketone bodies also used)
119
Ketonuria is a common indicator of...
Diabetes
120
What type of molecules are acetoacetate and b-hydroxybutyrate? What can this result in?
Strong organic acids
Ketoacidosis
121
How can acetone be excreted via the lungs? What is the clinical significance of this?
It is volatile
Characteristic smell of nail polish remover on breath
