Metabolism Flashcards
1
Q
Define metabolism
A
Mechanisms which couple the demand for energy (which is constant), with the fuel supply (which is intermittent)
2
Q
Define catabolism
A
Degradation of molecules to release energy
3
Q
Define anabolism
A
Synthesis of new molecules to store energy
4
Q
Describe the first stage of metabolism
A
Digestion in the GI tract - absorption and transport in the blood
5
Q
Describe stage 2 of metabolism
A
In the cell cytoplasm:
- Anabolic - nutrients built into storage molecules such as glycogen/protein/lipid
- Catabolic - nutrients broken down to pyruvic acid and acetyl CoA
6
Q
Describe stage 3 of metabolism
A
In mitochondria:
-Catabolism requiring oxygen to completely breakdown food and generate ATP
7
Q
How much oxygen do humans consume?
A
Roughly 350 ml O2/min but can increase 5 times during exercise
8
Q
Define oxidation
A
Gain of O2 from molecules or loss of hydrogen (or loss of electrons from molecules)
9
Q
Define reduction
A
Loss of O2 from molecules or gain of hydrogen (or addition of electrons)
10
Q
Name the two important coenzymes involved in metabolism
A
- Nicotinamide adenine dinucleotide (NAD)
- Flavin adenine dinucleotide (FAD)
11
Q
What is the role of the coenzymes in metabolism?
A
They transfer hydrogen/electrons, to oxidise molecules in reversible redox reactions during metabolism
12
Q
How much energy is released when ATP is hydrolysed to ADP + Pi?
A
Approximately -30.5 kJ/mol
13
Q
What is the first law of thermodynamics?
A
The total energy of a system (i.e. the universe) is constant - energy can neither be created nor destroyed… can be converted from one form to another
14
Q
Define Gibbs free energy of activation
A
The energy needed to transform substrates into the transition state
15
Q
Define Exergonic
A
Releases more energy than input (favourable)
15
Q
Define Exergonic
A
Releases more energy than input (favourable)
16
Q
Define endergonic
A
Requires more energy input than it yields (unfavourable)
17
Q
How is glucose transported into a cell?
A
Glut receptors e.g Glut2 and Glut4 - enhanced by insulin
18
Q
Is glycolysis catabolic or anabolic?
A
Catabolic
19
Q
Where does glycolysis take place within the cell?
A
Cytosol
20
Q
How many steps are there in glycolysis?
A
10
21
Q
What are the 3 stages of glycolysis?
A
- Investment
- Cleavage
- Energy Harvest
22
Q
How many ATP are used in glycolysis?
A
2
23
Q
How many ATP are generated in glycolysis?
A
4
24
What is the net gain of ATP in glycolysis?
2
25
What is step 1 of glycolysis?
- Phosphorylation of glucose at carbon 6
- Requires ATP (investment stage)
- Locks glucose inside the cell (maintains glucose gradient)
26
What enzyme is used in step 1 of glycolysis?
Hexokinase
27
What is step 2 of glycolysis?
- Conversion of glucose-6-phosphate (aldose) to fructose-6-phosphate (ketose)
- Glucose-6-phosphate - ring structure opens to enable isomerisation and subsequent ring closure - fructose-6-phosphate
28
What enzyme is used in step 2 of glycolysis?
Phosphoglucose isomerase
29
What is step 3 of glycolysis?
- Fructose-6-phosphate phosphorylated at carbon 1 - fructose 1,6-bisphosphate (FBP)
- Requires ATP (investment stage)
- Key regulatory point
30
What enzyme is used in step 3 of glycolysis?
Phosphofructokinase-1 (PFK)
31
What are steps 4 and 5 of glycolysis?
- Aldolase cleaves the FBP (6 carbons) into 2 trioses
- Glyceraldehyde-3-phosphate (GAP)
- Dihydroxyacetone phosphate (DHAP)
- These two are interchangeable and one can become the other through the use of the enzyme triose phosphate isomerase (step 5 technically)
- Only glyceraldehyde-3-phosphate used in the rest of glycolysis
32
What is step 6 of glycolysis?
- Oxidation & phosphorylation GAP by NAD+ and Pi
- First high energy intermediate - aldehyde oxidation (exergonic reaction) drives synthesis of the 1,3-bisphosphoglycerate
- Aerobic conditions - 2NADH + 2H+ enters citric acid cycle
33
What enzyme is used in step 6 of glycolysis?
Glyceraldehyde-3-phosphate dehydrogenase
34
What is step 7 of glycolysis?
- First formation of ATP (energy harvest)
| - The newly formed high-energy phosphate bond used to synthesise ATP and 3-phosphoglycerate (3PG)
35
What enzyme is used in step 7 of glycolysis?
Phosphoglycerate kinase
36
What is step 8 of glycolysis?
-3PG converted to 2PG - essential preparation for next energy harvest step
37
What enzyme is used in step 8 of glycolysis?
Phosphoglyceromutase
38
What is step 9 of glycolysis?
2PG dehydration to form phosphoenolpyruvate (PEP) - converts low energy ester bond of 2PG into high-energy intermediate phosphate bond
39
What enzyme is used in step 9 of glycolysis?
Enolase
40
What is step 10 of glycolysis?
Hydrolysis of PEP high-energy bond to generate ATP and pyruvate (physiological irreversible reaction)
41
What enzyme is used in step 10 of glycolysis?
Pyruvate kinase
42
What are the possible fates of pyruvate?
- Anaerobic - converted to lactate
- Aerobic - converted to Acetyl-CoA
- High cellular energy levels - fatty acids or ketone bodies
43
What happens after glycolysis in anaerobic conditions?
- Pyruvate + NADH + H+ <======>Lactate + NAD+
- For glycolysis to be able to continue in anaerobic conditions, NAD+ must be replenished
- When ATP demand is high and O2 depleted, homolactic fermentation regenerates NAD+
- Reversible reaction which enables glycolysis to continue for short amounts of time
44
What enzyme is used to convert pyruvate to lactate?
Lactate dehydrogenase
45
What mechanisms control rate of glycolysis?
- Key enzymes
- High [ATP] inhibit enzyme activity
- Intermediate substrates (e.g fructose-6-P) stimulate PFK activity
- High [citric acid] inhibits
- Low pH inhibits
- Hormones
46
What are the 3 key regulation enzymes in glycolysis?
- Hexokinase - allosterically inhibited by G-6-P
- Phosphofructokinase - most important site of control - first step to unique glycolysis - high [ATP] inhibits PFK by binding allosterically - high [AMP] activates PFK
- Pyruvate kinase - inhibited by high ATP and alanine and activated by FBP
46
What are the 3 key regulation enzymes in glycolysis?
- Hexokinase - allosterically inhibited by G-6-P
- Phosphofructokinase - most important site of control - first step to unique glycolysis - high [ATP] inhibits PFK by binding allosterically - high [AMP] activates PFK
- Pyruvate kinase - inhibited by high ATP and alanine and activated by FBP
47
Define the citric acid cycle
Redox reactions to harness energy via electron carriers (NAD+ & FAD), producing CO2
48
Define oxidative phosphorylation
Oxidation of coenzymes: electron transfer and reduction of O2 and ATP synthesis (ADP phosphorylation)
49
Explain acetyl CoA synthesis
In the mitochondrial matrix:
- pyruvate (& fatty acids/amino acids) are degraded into acetyl groups
- Acetyl groups are added to Coenzyme A (CoA) forming acetyl CoA
49
Explain acetyl CoA synthesis
In the mitochondrial matrix:
- pyruvate (& fatty acids/amino acids) are degraded into acetyl groups
- Acetyl groups are added to Coenzyme A (CoA) forming acetyl CoA
50
What is formed from each cycle of the citric acid cycle?
- 2 CO2
- 1 GTP
- 3 NADH + H+
- 1 FADH2
51
What is the 1st step of the citric acid cycle?
Condensation of the acetyl group (2-carbon) of acetyl CoA with the keto acid oxaloacetate (4-carbon) by citrate synthase
52
Is the first step of the citric acid cycle endergonic or exergonic?
Highly exergonic due to the thioester bond having a large -deltaG
53
How are NADH + H+ and CO2 formed in the citric acid cycle?
- A number of dehydrogenation steps occur in the citric acid cycle resulting in NADH + H+ formation
- The keto acids formed are quite reactive - they can be decarboxylated which results in CO2 released
54
How is GTP generated in the citric acid cycle?
- CoA bonds with one of the carbon chain molecules to form succinyl-CoA
- The high energy thioester bond of succinyl-CoA generates GTP on conversion to succinate
54
How is GTP generated in the citric acid cycle?
- CoA bonds with one of the carbon chain molecules to form succinyl-CoA
- The high energy thioester bond of succinyl-CoA generates GTP on conversion to succinate
55
Where does FAD come from?
It is a coenzyme formed from the vitamin riboflavin (vitamin B2)
56
FAD in the citric acid cycle
- FAD bound to the enzyme succinate dehydrogenase (only citric acid cycle enzyme bound to the inner mitochondrial membrane)
- FAD reduced to FADH2
- Reoxidised via the electron transport chain
57
How is the citric acid cycle regulated?
Inhibition of enzymes involved in the citric acid cycle by levels of:
- ATP
- Acetyl CoA
- NADH
- CO2
58
How much ATP will one molecule of NADH + H+ generate?
Roughly 2.5 ATP
59
How much ATP will one molecule of FADH2 generate?
Roughly 1.5 ATP
60
What is the metabolic waste product of the citric acid cycle?
Carbon dioxide
61
What is the first part of the electron transport chain?
Reduced coenzymes deliver electrons to complexes I & II (NADH + H+ delivers to I and FADH2 delivers to II)
62
What happens to each complex as the electrons are transferred through the chain?
Each complex is reduced, then oxidised
63
What does the energy released in the electron transport chain do?
Pumps H+ into intramembranous space
64
What transfers the electrons between complexes in the electron transport chain?
- Coenzyme Q (from I and II to III)
| - Cytochrome c (from III to IV)
65
What is the action of complex IV in the citric acid cycle?
Complex IV combines 2H+ and 1/2O2 to form H2O
66
Why are the H+ ions pumped into the intra membranous space?
Because the energy generated from this proton gradient synthesises ATP
67
Name and action of complex I
NADH-Q reductase - oxidises NADH + H+, reduces coenzyme Q
68
Name and action of complex II
Succinate-Q-reductase - oxidises FADH2, reduces coenzyme Q
69
Name and action of complex III
Q-cytochrome C oxidoreductase - oxidises coenzyme Q, reduces cytochrome c
70
Name and action of complex IV
Cytochrome C oxidase - oxidises cytochrome c, reduces O2 to H2O
71
What inhibits the electron transport chain?
Cyanide:
- Found in smoke, apricot & other fruit pips, cassava
- Symptoms: confusion, dizziness, vomiting seizure
- Binds to iron in the enzyme, prevents the electron transport chain from working, halts ATP production
Carbon monoxide also binds to the same enzyme
72
What enzyme to cyanide and carbon monoxide both bind to to inhibit the electron transport chain?
Cytochrome C oxidase
73
How is ATP synthesised after the electron transport chain?
The proton gradient creates:
- A pH gradient - H+ concentration in matrix lower than in intermembranous space
- A voltage across the membrane
Both conditions strongly attract H+ back inside the matrix
Only free permeable region is via complex V - ATP synthases (molecular rotary motors)
74
Energy yield of cellular respiration
- Glycolysis - Net gain of 2 ATP per glucose molecule
- Citric Acid Cycle - Total gain of 2 ATP from 2 pyruvate molecules
- Electron transport chain/oxidative phosphorylation - 28 ATP generated
- Total (accounting for shuttle costs) = about 30 ATP per glucose molecule
75
What happens in the absorptive/fed state?
Nutrients are plentiful - fuels broken down and excess stored (anabolism)
76
What can insulin promote?
- Glucose uptake
- Fatty acid synthesis
- Protein synthesis
77
What happens in the postabsorptive/fasting state?
Storage molecules broken down for energy (catabolism) - biosynthesis slows down
78
What is the primary aim of the postabsorptive state?
To maintain blood glucose levels within homeostatic range of 70 - 110mg/dl or 4-7mmol/L
79
Where does blood glucose come from in the postabsorptive state?
Glycogenolysis:
- liver glycogen, roughly 100g (enough for about 3-5 hours of activity)
- muscle glycogen (only utilised within muscle)
Gluconeogenesis (formation of glucose from noncarbohydrate molecules):
- occurs mainly in the liver
- lipolysis of fatty acids to generate glycerol which will then become glucose
- catabolism of muscle protein - deamination of amino acids which is then used to make glucose
80
Describe glycogen
- A branched polysaccharide storage molecule for glucose
- Liver and skeletal muscle are the main glycogen reservoirs
- Glycogen stores change constantly, with changes in nutritional states
81
How does the liver utilise glycogen?
- Maintains blood glucose levels
| - Enough glycogen for 3-5 hours of moderate exercise or 12 hours of overnight fast
82
How do muscles utilise glycogen?
Store glycogen for muscle contraction - channelled into glycolysis (not released into bloodstream)
82
How do muscles utilise glycogen?
Store glycogen for muscle contraction - channelled into glycolysis (not released into bloodstream)
83
Define glycogenesis
Synthesis of glycogen from glucose
84
When does glycogenesis occur?
When glucose supplies exceed demand for ATP
85
Define glycogenolysis
Breaking down of glycogen to release glucose
86
How is glycogenolysis stimulated?
Stimulated by low blood glucose
87
Explain the process that forms glycogen from glucose?
- Glucose
- Glucose-6-phosphate
- Glucose-1-phosphate
- Glycogen
87
Explain the process that forms glycogen from glucose?
- Glucose
- Glucose-6-phosphate
- Glucose-1-phosphate
- Glycogen
88
What can promote glycogenolysis?
- Glucagon
- Adrenalin
- Cortisol
- Growth hormone
89
What enzymes are required for glycogenolysis?
- Glycogen phosphorylase
| - Debranching enzyme
90
Explain glycogenolysis in the liver
- Glycogen
- Glucose-1-phosphate
- Glucose-6-phosphate
- Glucose
- Released into bloodstream (Glut2), for uptake by all cells, but especially brain and RBCs
91
Explain glycogenolysis in muscle
- Glycogen
- Glucose-1-phosphate
- Glucose-6-phsophate
- No G-6-Pase enzyme, instead G-6-P enters glycolysis
92
Define gluconeogenesis
Formation of glucose from non carbohydrate sources
93
What are examples of non carbohydrate sources used in gluconeogenesis?
- Glycerol from triglycerides
- Glucogenic amino acids (alanine & glutamine)
- Lactate
94
How is most fat stored?
- Triglycerides/ triacylglycerols
| - Glycerol molecule undergoes condensation with 3 fatty acids
95
Describe lipolysis and how glycerol can be used in respiration
- Fat breakdown into glycerol and fatty acids is known as lipolysis - reverse of lipogenesis
- Fatty acids and glycerol released from adipose tissue and metabolised mainly by the liver
- Glycerol feeds into gluconeogenesis but can also be utilised by most cells - converted into glyceraldehyde-3-phosphate then goes through glycolysis (1/2 glucose = 15 ATP aerobically)
96
Describe how fatty acid chains are used in respiration
-Undergo beta-oxidation
-Broken down into 2-carbon acetic acid and fused to Coenzyme A giving acetyl CoA
-FAD and NAD+ reduced feeding into electron transport chain
Acetyl-CoA goes into the citric acid cycle
97
When will ketone bodies form?
Ketone bodies are formed when carbohydrate intake is inadequate and the beta-oxidation product - acetyl-CoA - is in excess (for citric acid cycle metabolism)
98
What is the limiting factor of the citric acid cycle when glucose is low and why?
Oxaloacetate is the limiting factor when glucose is low because it is converted to pyruvate in gluconeogenesis
99
What ketone bodies could acetyl-CoA be converted to?
- Acetoacetate
- 3-hydroxybutyrate
- Acetone
100
What happens to excess protein?
- Excess protein cannot be stored
| - Amino acids are oxidised for energy or converted to fat
101
Define deamination
Removal of amine group (NH2) prior to oxidation or storage
101
Define deamination
Removal of amine group (NH2) prior to oxidation or storage
102
Define transamination. Why is it useful?
- Process by which some amino acids can be converted to keto acids - e.g. amine group transferred to keto-glutamate = glutamic acid
- Modified keto acids generate pyruvate or keto acid intermediates for citric acid cycle (or converted to glucose - gluconeogenesis)
102
Define transamination. Why is it useful?
- Process by which some amino acids can be converted to keto acids - e.g. amine group transferred to keto-glutamate = glutamic acid
- Modified keto acids generate pyruvate or keto acid intermediates for citric acid cycle (or converted to glucose - gluconeogenesis)
