M3: Metabolism Flashcards
1
Q
Why is ATP suited to act as the energy currency in our cells?
A
It has high phosphate so therefore carries plenty of energy
2
Q
If a reaction has a -ve delta G, it is spontaneous or non-spontaneous
A
Spontaneous
3
Q
How can a non-spon reaction take place?
A
When delta G is +ve meaning there is less energy in the reactant than the product and coupling reaction needs to take place
4
Q
What type of reaction happens to fuel molecules in the pathways
A
> involving ADP and ATP
> Redox rections
5
Q
What is meant by the term ‘reducing equivalent’?
A
The transfer of hydrogen atoms
H = H+ + e- (proton and electron)
6
Q
What are the key properties of coenzymes in relation to he metabolic pathways?
A
> Not a carrier of electrons
carriers of acyl groups
2 forms
7
Q
What are the major coenzymes involved in the ATP synthesis process
A
NAD
FAD
Coenzyme A
8
Q
In which metabolic pathways do each of these coenzymes function?
A
NAD - undergoes a 2 electron reduction
FAD - undergoes a 2 electron reduction
CoA - carries acyl groups
9
Q
What do each of the coenzymes carry what are their 2 forms?
NAD, FAD, CoA
A
NAD - single and double bond
FAD - single and double bond
CoA - free coenzymes (CoASH) and acyl group attached (AcCoA)
10
Q
What organisms can use glucose as a fuel molecule?
A
All
11
Q
Where in the cell does glycolysis occur in mammals?
A
cytoplasm or mitochondria
12
Q
In which cells of the human body is glucose essential or favoured as a fuel? why?
A
Essential for blood because they do not have mitochondria
Favoured in the brain as it has high energy requirements
Favoured in the eye because the oxygen in blood vessels and mitochondria would refract light int he optical path
13
Q
What are the 2 phases of glycolysis?
A
Energy investment phase
Energy pay off phase
14
Q
in which molecules is energy conserved/captured in glycolysis?
A
ATP and NADH
15
Q
Why is oxidation of glyceraldehyde-3-phosphate essential for glycolysis to make an ATP profit?
A
The addition of phosphate powered by oxidation of G-3-P does not require ATP
16
Q
The ATP produced in glycolysis is produced by what type of reaction? What are the key aspects of this type of reaction?
A
substrate-level phosphorylation.
> direct
> energy comes from substrate
17
Q
What is the overall reaction of glycolysis?
A
Glucose + 2NAD+ +2ADP + 2Pi –> 2 pyruvate + 2NADH + 2ATP + 2H+
18
Q
What are the two possible fates of pyruvate in humans?
A
Anaerobic and aerobic
19
Q
Why is it important that lactate is produced in animals under anaerobic conditions?
A
Allows for the regeneration of NADH+
20
Q
Fatty acids used as a fuel molecule are obtained from the breakdown of what stoppage molecule in our adipose tissue?
A
Albumin
21
Q
Why does the body store fats rather than carbohydrates?
A
fatty acids are more reduced than carbohydrates
22
Q
The attachments of fatty acids to coenzyme A is called what?
A
fatty acyl-CoA
23
Q
In terms of ATP hydrolysis, what is the “cost” of activating fatty acids?
A
additional energy input
24
Q
Where does B-oxidation occur?
A
mitochondria
25
How is fatty-acyl CoA transported into the mitochondria?
must pass through the two membranes (outer and inner) and into the matrix
26
How is energy released during the oxidation of fatty acids harnessed?
conversion between ATP--> AMP --> ADP --> ATP
27
What are the 4 reactions that take place in B-oxidation?
1. oxidation
2. hydration
3. oxidation
4. cleavage
28
What is the product of B-oxidation, and where is this molecule further oxidised:?
Fatty acyl-CoA shortened by 2 carbons and is further oxidised it successive circles.
29
Palmite is a 16 carbon fatty acid, how many round of B-oxidation will occur to fully oxidise palmate, and what will be the net yield of this oxidation?
7
| 7NADH, 7 FADH and 8 acetyl-CoA
30
Where in the cell does the CAC occur?
Mostly in the mitochondria
31
Carbon enter the CAC in the form of acetyl-CoA, where does the acetyl CoA come from?
glucose and fatty acids
32
What are the 2 major parts of the CAC?
> release of C
| > regeneration of the starting molecule
33
The first key reaction in the CAC is a condensation reaction, what is the product of this reaction and where does the energy for this reaction come from?
> 6 C citrate
| > hydrolysis of CoA from acetyl-CoA
34
What key events happen in the oxidative decarboxylation?
oxidation then decarboxylation
35
The conversion of succinyl CoA is succinate enables a substrate level phosphorylation. Describe what happens in a substrate level phosphorylation
The direct use of energy from a substrate molecule to drive the synthesis of ATP or equivalent. the P dos not have to come from substrate.
36
What is the overall CAC reaction?
acetyl-CoA + 3NAD+ + FAD + 2H2O + GDP +Pi --> 2CO2 + CoASH +3NADH + 3H+ + FADH2 + GTP
37
How does Sodium fluorocetate inhibit the CAC?
Flourocitate is converted into a substrate that binds tightly to aconitase and inhibits the enzyme
38
What part of the amino acid can be feed into metabolic pathways?
keto acids
39
What is transamination?
when some amino acids are deaminated by transferring their amino group to a keto acid.
1. Amino group is transferred from the amino acid to the pryridoxal phosphate
2. Amino groups is transferred pridoxamine phosphate to the keto acid.
40
What is a aminotransferase and what is its role?
enzyme that catalyses transamination
41
Write the general reaction catalysed by an aminotransferase
Glutamate + alpha-keto acid --> alpha-ketoflutarate + alpha-amino acid
42
What role does the coenzyme pyridoxal phosphate play in an aminoransferase reaction?
carries amino group from the amino acid to the keto acid
43
What happens to amino groups when amino acids are being used as a fuel molecule?
they are realised into solution
44
oxidative phosphorylation refers to the coupled process of what 2 pathways?
> Electron transport through the ETC
| > phosphorylation of ADP to ATP by ATP-synthase
45
In order to study the ETC, we generate a preparation of mitochondria. How are these preparations made?
```
Isolate the mitochondria form cells
> tissue
> homogenerate
> supernatant
> pellet of mitochondria
```
46
Where in the mitochondria does the ETC take place?
matrix, inner membrane and inter membrane space
47
What is the role of electron carriers in the ETC?
transport electrons
| UQ or CoQ and CytC
48
The ETC oxidises reduced coenzymes. Where do these reduced coenzymes come from?
NADH and FADH2
49
The energy released by the movement of electrons up their reduction potential through the ETC causes what to be translocated across the mitochondrial inner membrane?
protons
50
If the ETC is inhabited, what are the consequences?
```
>Stops the flow of electrons
> there is no protein gradient
> Build-up of reduces co-enzymes
>no oxidising power for other pathways
> reactive oxygen species are produced
```
51
At which complex of the ETC is NADH oxidised? How many electrons does this release into the ETC and how many protons are pumped across the membrane at this complex?
> Complex I
> 2 electrons released
> 4 protons pumped
52
At which coupled of the ETC is FADH2 oxidised? How many electrons does this release into the ETC and how many protons are pumped across the membrane at this complex?
> Complex II
> 2 electrons released
> no protons are pumped
53
Why is the SDH enzyme shared between the ETC and the CAC?
because they cross over in the inner membrane
54
What mobile electron career do Complex I and II pass electrons to?
UQ/CoQ
55
Where does this electron carrier deliver the electrons?
complex III ( 1 electron at a time)
56
What electron carrier does complex III pass electrons to?
Cytochrome C (CytC)
57
This passing of electrons at complex III causes how many protons to be pumped across the inner membrane?
4 protons
58
What reaction takes place at Complex IV?
reduces oxygen to water
59
For each NADH oxidised in the ETC, how many protons are pumped?
8 + 8 + 2 = 10 protons
60
For each FADH2 oxidised in the ETC, how many protons are pumped?
4 + 2 = 6 protons
61
What is the proton motive force (pmf) and what role does it play in ATP generation?
electrochemical proton gradient across the inner mitochondrial membrane.
62
What are the 2 components of proton-motive force (pmf)?
> chemical gradient (pH) as a result of the different H+ concentrations on either side.
> electrical gradient as a result on the charge difference across the membrane
63
Describe the experimental evidence that supports chemiosmotic coupling hypothesis for ATP synthesis rather than ATP being made in a substrate level phosphorylation in the ETC?
Mitochondria was isolated form other cells. When treated with strong detergent, it was solubilised all membranes. the ETC did not work. When treated with mild detergent and removed only the outer membrane the ETC still worked but there was no ATP made. Therefore, ATP is not synthesises in the ETC and the outer membrane is required for gradient.
64
How does ATP-synthase act like a turbine to generate ATP?
there are root subunits (move) and stator subunits (don't move). the proton flow drive the rotor movement. Rotor movement causes conformational changes in the stator that drives ATP synthesis.
65
What is an uncoupler?
Shuttles H+ form the inter membrane space to the matrix, thus dissipating the proton gradient.
66
What effect do uncouplers have an oxidative phosphorylation?
ETC functions
| No ATP is made
67
How many protons are required to generate 1 ATP?
4
68
1 NADH is entering the ETC leads to 10 protons being pumped. How many ATP will this produce?
10/4 = 2.5
69
1 FADH2 entering the ETC leads to 6 protons being pumped. How many ATP will this produce?
6/4 = 1.5
70
In what organ of the body does ethanol metabolism primary take place?
liver
71
What receptor in the central nervous system is activated by alcohol? What is the biochemical effect of this activation?
GABAa
alcohol binds to the rector. When activated, selectively conducts Cl- ions causing inhibitory effect by reducing chance of successful action potential
72
Write the reaction that oxidises ethanol to acetate
Ethanol -> acetaldehyde -> acetate
73
What are the names of the 2 enzymes involved in the reaction of ethanol to acetate?
Alcohol dehydrogenase
| Aldehyde dehydrogenase
74
Which is the rate-limiting step?
ethanol -> acetaldehyde
75
How can the acetate molecule be further metabolised as a fuel molecule?
with the help of acetyl CoA synthetate where CoA and ATP is helped to form AMP + PPi and acteyk CoA
76
How does the oxidation of ethanol as a fuel differ to oxidation of glucose and fatty acids?
>glucose -> pyruvate -> pyruvate with help of amino acids
>Fatty acids -> fatty acyl-CoA actiavted fattu acids with B-oxidation
> ethanol -> acetaldehyde-> acetate
All going to acetyl CoA before CAC
77
Is ethanol oxidation subject to feedback regulation?
yes?
78
If large amounts of ethanol are being oxidised, what is the consequences on other metabolic pathways?
increases NADH:NAD+
> slows CAC, electron transport, fatty acid oxidation, pyruvate dehydrogenase and glycolysis.
> causes private -> lactate decreasing pH
79
What is microsomal cytochrome P450 ethanol oxidising system (MEOS)?
using oxidase to oxidise ethanol. It is not as effective and can effect medication
80
What toxic effects can chronic alcohol consumption have on the body?
```
> toxic acetaldehyde reactive oxygen species
> fatty liver; inflammation
> alcohol hepatitis
> necrosis
> cirrhosis
> coma and death
```
81
How is ATP store in the body?
It is not stored, it is made when required.
82
Why does our body need fuel stores?
to maintain a supply of glucose between meals, to provide immediate fuel for increased activity and for long periods when food intake may be inadequate
83
What is the major storage molecule for each of the fuel stores?
> Triacylglycerol
> Protein
> Glycogen
> circulating fuels
84
Where in the body are each of these fuel stores located?
```
Triacylglycerol = Adipose tissue
Protien = muscle
Glycogen = muscle and liver
CF = Glucose, fatty acids and tracylglycerols
```
85
What are the 2 major components that make up TAG, form what fuel type are these components obtained?
fatty acids and glycerol
| adipose tissue
86
How are TAGs synthesised form excess dietary fat?
activation of the fatty acids to acyl-CoA. Esterfication of acyl groups to glycerol 3-phosphate
87
Where is glycogen synthesised?
liver and muscle
88
What hormone(s) is involved in stimulating the synthesis of fuel stores?
insulin
89
What hormone(s) is involved in the mobilisation of fuel stores?
Adrenaline and glucagon
90
What enzyme(s) help to break down the TAG stores?
inorganic pryrophosphate
91
What is the involvement of G-protein coupled receptors in the mobilisation of TAGs?
As long as the signal is bound to the receptor, many copies will be made.
92
The body only has a limited capacity to store glucose as glycogen, so excess glucose is converted to acids. Where does this occur?
liver cytosol
93
Different tissues prefer to sue different fuels. What fuels can be used in the liver, heart and muscles?
fatty acids
94
Why can the brain only use glucose as a fuel source?
because it cannot use fatty acids
95
Why can red blood cells only use glucose? is this glucose being oxidised to provide energy?
because there is no mitochondria so cannot oxidise fats. The glucose is being oxidised.
96
What are the main fuel stores mobilised during starvation?
Triacylglyercol
97
What is the main hormone that regulates metabolised during starvation?
glucagon
98
TAGs are very important in starvation, broken down into glycerol and FFAs, how are these products used to fuel starving body?
glycerol enters blood and goes into the liver
| FFAs are used by all aerobic tissues except the brain
99
How is liver glycogen mobilised?
Glycogenolysis
| Glycogen + Pi -> glucose-1-phosphate -> glucose-6-phosphate + H20 -> glucose and Pi
100
What organ benefits from this glycogen and for how long?
brain
101
How is this organ fueled after glycogen stores are depleted?
using muscle stores, red blood cells and adipose tissue???
102
What are the substrates for gluconeogenesis, and where do they come from?
Lactate from muscle glycogen
Alanine from muscle protein
Glycerol from adipose tissue (TAG)
103
Why can't the brain be provided with fuel from gluconeogenesis alone?
The brain lack fuel stores and therefore requires continuous supply
104
What alternative pathway is used to provide the brain with fuel once gluconeogenesis must slow down?
ketone bodies
105
Where are ketone bodies synthesises?
liver and fatty acids
106
What molecule provides the substrate to synthesise ketone bodies?
TAG from adipose tissue
107
Exercise may be aerobic or aerobic. What is the difference and under what conditions Wille each occur?
```
Anaerobic:
- high intensity
- rapid generation
- short periods
- e.g springing
Aerobic:
- low intensity
- prolonged, sustained excercise
- long distance running
```
108
For both aerobic and anaerobic exercise, what has the main ways in which muscle regenerates ATP?
```
Anaerobic:
- phosphocreatine
- glycogen
Aerobic:
- Oxidation of glucose and fatty acids
```
109
What is phosphocreatine, and under what circumstances will it be used?
- 20 micromol/g (10 secs)
- high energy phosphate compound
- phosphate transferred to ADP to make ATP
110
What enzyme is involved in the breakdown of phosphocreatine?
creatine kinase
111
How is glycogen mobilised to provide ATP during aerobic exercise?
mobilised to glucose-1-phosphate --> glucose-6-phodphate
112
What enzyme is important in this glycogen mobilisation?
glycogen phosphorylase
113
What fuel sources are used to provide energy for aerobic exercise?
blood supplies O2
114
What are the 2 major types of muscle cell?
```
Type 1 (red)
Type 2 (white)
```
115
What are the properties of these 2 types of muscle cell?
Type 1
- slow contraction, low power output, high endurance, capillary density and myoglobin content, oxidative metabolism
Type 2
- fast contractions, low endurance, low mitochondria, high glycogenolytic and glycolytic enzyme activity and glycolytic metabolism
116
under what types of exercise do these muscle fibres function? Why?
Type 1. slow twitch - marathon running
| Type 2. fats twitch - high jumping
117
What are the major clinical symptoms of diabetes?
- fatigue
- weight loss
- intense thirst
- frequent urination
- hyperglycaemia
- glycosuria
- ketones
118
How do type I and type II differ?
Type I is an autoimmune destruction whereas Type II is a resistance to action of insulin
119
What is insulin and where is it produced?
it is a peptide hormone that is synthesised in the pancreas by B cells. It is then secreted in response to high glucose after a meal
120
what tissues are the major targets of insulin?
liver, muscle and adipose tissue
121
How does insulin maintain blood glucose levels after a meal?
blood glucose levels rise after a meal and insulin brings it down
122
Insulin is absent in type I diabetes, what is the metabolic consequence of this?
has higher plasma glucose levels and more flucuations
123
How does blood glucose concentration fluctuate over the course of a day in a person with type I diabetes vs. an unaffected person?
after a meal, the unaffected will have a higher peak of insulin in blood glucose than Type I although they will come back down much quicker and further after the meal. When a snack in consumed, the type I diabetes person will not show a rise but the unaffected person will.
124
What treatments may be appropriate fr someone with type II diabetes?
- weight loss
- increased exercise
- hypoglycaemic drugs
125
What does BMI refer to?
Body mass index
126
How would you calculate a persons BMI?
weight (kg) / height ^2 (m)
127
How is obesity defined from a BMI perspective?
BMI > 30
128
What factors are said to be causes of obesity?
energy expenditure and metabolic rate
129
What is the purpose of brown adipose tissue?
thermogenic tissue
130
What are the characteristics of brown adipose tissue, compared to white adipose tissue?
- rich in mitochondria
| - abundant cristae
131
how do uncoupling proteins affect the mitochondria? What effect food this have on ATP production?
regulates proton channels in the membrane.
| 'uncouple' nATP synthesis - electrochemical potential gradient dissipates, releasing heat.
132
Biochemical signaling of which molecule aims to control food intake?
leptin
133
Where in the body is leptin synthesises?
adipose tissue
134
If leptin is missing, what effect does this have on appetite and energy expenditure?
decrease exercise and increase food intake
135
What are some possible molecular targets to treat obesity?
food breakdown
satiety signals
Mitochondrial and brown fat
