Block 1 - Metabolism Flashcards
1
Q
What is the primary source of energy for cells?
A
Electrons with negative redox potential (high energy electrons)
2
Q
What do cells need for anabolic processes?
A
Reductive power provided by high energy electrons
3
Q
What do cells require to build cellular components?
A
A source of carbon
4
Q
How do plants synthesize macromolecules?
A
Using sunlight as energy
5
Q
What is the process of catabolism?
A
Decomposition of large complex organic molecules into small molecules
6
Q
What are the characteristics of catabolism?
A
- Degradative
- Oxidative
- Energy is liberated
- Converging
7
Q
What is the process of anabolism?
A
Construction of large complex molecules from small molecules
8
Q
What are the characteristics of anabolism?
A
- Biosynthetic
- Reductive
- Energy is required
- Diverging
9
Q
What are oxidation-reduction reactions also known as?
A
Redox reactions
10
Q
What happens during oxidation in redox reactions?
A
Loss of electrons
11
Q
What happens during reduction in redox reactions?
A
Gain of electrons
12
Q
What is a reducing agent?
A
An electron donor that causes reduction in another molecule and is itself oxidised
13
Q
What is an oxidising agent?
A
Receives electrons, causes oxidation in another molecule and is itself reduced
14
Q
List the oxidation states of carbon from most reduced to most oxidised.
A
- Alkanes (found in fats)
- Alcohol (found in carbohydrates)
- Aldehyde
- Carboxylic acids
- Carbon dioxide (final product of catabolism)
15
Q
What is a key result of glucose oxidation?
A
Releases energy
16
Q
Why does glucose oxidation happen in steps?
A
- Reduce activation energy
- Reduce free energy released
- Provide convenient control points
- Allow integration with other cellular metabolism
17
Q
What is the role of organic compounds in chemotrophs?
A
They are oxidised to release high energy electrons
18
Q
What are the electron carriers in organic cofactors?
A
- NAD+ + 2H+ is reduced to NADH + H+
- FAD + 2H+ is reduced to FADH2
19
Q
What is a terminal electron acceptor reduced to in aerobic conditions?
A
O2 to H2O
20
Q
What are enzymes?
A
Proteins that catalyse the conversion of a substrate into a product
21
Q
What do enzymes often require to function?
A
Co-enzymes such as ATP
22
Q
What is the function of oxidoreductases?
A
Catalyse oxido-reductions
23
Q
Give an example of an oxidoreductase.
A
Alcohol dehydrogenase
24
Q
What is the function of transferases?
A
Transfer a group into a substrate
25
Give an example of a transferase.
UMP kinase
26
What is the function of hydrolases?
Catalyse the hydrolysis of various bonds
27
Give an example of a hydrolase.
Aminoacyl-tRNA hydrolase
28
What is the function of lyases?
Cleaves bonds by means other than hydrolysis or oxidation
29
Give an example of a lyase.
Pyruvate decarboxylase
30
What is the function of isomerases?
Catalyse changes within one molecule
31
Give an example of an isomerase.
DNA topoisomerase
32
What is the function of ligases?
Catalyse the joining of two molecules with concomitant hydrolysis of the diphosphate bond in ATP
33
Give an example of a ligase.
DNA ligase (ATP)
34
What does a kinase do?
Transfers a phosphate group
35
What does an isomerase do?
Rearranges the molecule
36
What does a synthase do?
Makes a molecule from parts
37
What does a dehydrogenase do?
Removes hydrogen
38
What does a phosphatase do?
Removes phosphate from protein
39
40
What are the two primary polysaccharides that contain more than half of all organic carbon?
Starch and cellulose
41
Which cell types require glucose as an energy source?
* Erythrocytes
* Retina
* Renal medulla
* Brain
42
What percentage of the oxygen requirement in a resting person does the brain account for?
About 20%
43
Describe the difference between alpha glucose and beta glucose.
Alpha glucose has the hydroxy group at the bottom of the 1st carbon; beta glucose has the hydroxy group at the top of the 1st carbon.
44
Name two five-carbon sugars.
* Ribose
* Deoxyribose
45
What is the term for two sugars joined together?
Disaccharides
46
What type of glycosidic linkage is formed when the bond between sugars is pointing downwards?
Alpha glycosidic linkage
47
What type of glycosidic linkage is formed when the bond between sugars is pointing upwards?
Beta glycosidic linkage
48
Which disaccharide is formed by linking glucose and fructose?
Sucrose
49
What is maltose formed from?
Two glucose linked together via an alpha bond
50
What is cellobiose formed from?
Two glucose linked via a beta bond
51
How are carbons numbered in sugars?
Starting from the right and going in a clockwise direction
52
What are polysaccharides?
Chains of sugars joined together, can be a mix of beta and alpha glycosidic linkages
53
How does glucose enter cells?
Via passive facilitated diffusion through glucose transporters
54
What triggers the conformational change in glucose transporters?
Binding of glucose to the outside
55
What is the function of GLUT1?
Transport glucose into the brain with low Km levels
56
What is the function of GLUT2?
Transport glucose in the liver and pancreatic beta-cells with high Km, insulin independent
57
What is the function of GLUT4?
Transport glucose into muscle and adipose tissue, insulin dependent
58
What is the function of GLUT5?
Transport fructose in the gut
59
What is the first stage of glycolysis?
Glucose is trapped and destabilised
60
What enzyme converts glucose to glucose 6-phosphate (G6P)?
Hexokinase
61
What is produced when phosphofructokinase converts fructose 6-phosphate (F6P)?
Fructose 1,6-bisphosphate (FBP)
62
What are the two interconvertible three-carbon molecules formed in Stage 2 of glycolysis?
Dihydroxyacetone phosphate (DAP) and glyceraldehyde 3-phosphate (G3P)
63
What is the main outcome of Stage 3 of glycolysis?
Generation of ATP
64
What enzyme converts G3P into 1,3-bisphosphoglycerate (BPG)?
Triose phosphate dehydrogenase
65
What are the energy-investing reactions in glycolysis?
Stages 1 and 2
66
What are the energy-harvesting reactions in glycolysis?
Stage 3
67
What are the two major cellular needs addressed by glycolysis?
* Production of ATP
* Provision of building blocks for synthetic reactions
68
What are potential control points in glycolysis?
Enzymes catalyzing essentially irreversible reactions
69
What is the ΔG of the reaction catalyzed by hexokinase?
-33.5 kJ mol-1
70
Name a negative modulator of phosphofructokinase.
* ATP
* Citrate
* H+
71
Name a positive modulator of phosphofructokinase.
AMP
72
What does the ATP/AMP ratio indicate?
The energy change in the cell
73
What happens if the cell only contains AMP and Pi?
It is ‘discharged’
74
Which molecule is the positive regulator when ATP is rapidly used up?
AMP
75
What is NAD+ derived from?
Vitamin niacin
76
What does glycolysis reduce NAD+ to?
NADH + H+
77
How is NAD+ regenerated?
Through the metabolism of pyruvate
78
What is the primary product of alcohol fermentation?
Ethanol
79
What is produced during lactic acid fermentation?
Lactate
80
What happens to pyruvate in aerobic conditions?
It is further oxidised, releasing much more energy
81
Where does lactic acid fermentation occur?
In many microorganisms and muscle during anaerobic exercise
82
What causes soreness during anaerobic exercise?
Low pH due to lactic acid accumulation
83
Where is lactate eliminated from the body?
In the liver, heart, and resting/relaxed working muscles
84
How does training affect lactate production?
Diminishes lactate production
85
What does plasma lactate during exercise predict?
Endurance and performance
86
What is the reaction summary for lactic acid fermentation?
C6H12O6 + 2ADP + 2Pi -> 2 Lactate + 2ATP
87
Why do many cells undergo fermentation?
To complete anabolic reactions needing a carbon source
88
What is found in the inner membrane of mitochondria?
Proteins for electron transport chain, ATP synthase, and transport proteins
89
What does the matrix of the mitochondria contain?
Enzymes of the TCA or Krebs cycle
90
How does pyruvate enter the mitochondria?
Via specific transporter
91
What does the pyruvate dehydrogenase complex (PDC) catalyze?
The oxidative decarboxylation of pyruvate to acetyl-CoA
92
What are the components of the PDC?
3 enzymes (E1, E2, E3) and 2 control enzymes (kinase and phosphatase), plus 5 coenzymes
93
What are the 5 coenzymes involved in the PDC?
* Thiamine
* Lipoic acid
* Coenzyme A
* FAD
* NAD+
94
What is the significance of the PDC's activity?
It is the major determinant of glucose oxidation in well oxygenated tissue (in vivo)
95
Is the reaction catalyzed by the PDC reversible?
No, it is irreversible
96
What is produced from the reaction in the PDC?
Acetyl-CoA
97
What varies in anaerobic catabolism among organisms?
The outcomes depending on electron acceptor availability
98
What are the differences between aerobic and anaerobic conditions?
* Energy yield
* Anabolic precursor availability
99
What is the total number of reactions in the TCA Cycle?
Eight reactions in total.
100
What type of unit condenses with a four-carbon unit in the TCA Cycle?
A two-carbon unit from acetyl-CoA.
101
What is produced during the decarboxylation of the six-carbon unit in the TCA Cycle?
CO2.
102
How many oxidation reactions occur in the TCA Cycle?
Four oxidation reactions.
103
What is formed during substrate level phosphorylation in the TCA Cycle?
One GTP.
104
What is the initial substrate that is oxidized to acetate in the TCA Cycle?
Pyruvate.
105
What is the byproduct of the oxidation of pyruvate to acetate?
NADH and CO2.
106
What two components combine to form citrate in the TCA Cycle?
Two-carbon acetyl group and four-carbon oxaloacetate.
107
What enzyme catalyzes the conversion of citrate to isocitrate?
Aconitase.
108
What is produced when isocitrate is oxidized to alpha-ketoglutarate?
NADH and CO2.
109
What does succinyl CoA convert to upon releasing coenzyme A?
Succinate.
110
What is generated from the energy released when succinyl CoA converts to succinate?
GTP.
111
What is oxidized to fumarate in the TCA Cycle?
Succinate.
112
What enzyme converts fumarate to malate?
Fumarase.
113
What is the final product of the TCA Cycle before it re-enters the cycle?
Oxaloacetate.
114
All enzymes of the TCA cycle are located in which part of the cell?
Mitochondrial matrix.
115
Which enzyme of the TCA Cycle is integrated in the inner mitochondrial membrane?
Succinate dehydrogenase.
116
What can all products of stage 2 metabolism give rise to?
Acetyl-CoA.
117
What does each turn of the TCA Cycle involve in terms of carbon uptake and release?
Uptake of two carbon atoms and release of two carbon atoms as CO2.
118
How many pairs of electrons are transferred to NAD+ during each turn of the TCA Cycle?
Three pairs of electrons.
119
What does high ATP, NADH, and acetyl-CoA indicate about energy levels?
Plenty of energy.
120
What does high ADP and NAD+ signify regarding energy levels?
Lack of energy.
121
What is produced as a result of one turn of the TCA Cycle?
3 NADH + H+, 1 FADH2, 1 GTP, 2 CO2.
122
The TCA cycle is a central metabolic pathway that integrates processes from what?
Several carbon sources.
123
Fill in the blank: The TCA cycle is not exclusive to _______ metabolism.
glucose.
124
Define 'OXPHOS'
OXPHOS is the final stage of cellular respiration in aerobic organisms and its driven by the energy released during stepwise oxidation-reduction chain reactions in electron transporting systems.
125
Outline electron flow in the respiratory chain.
Electrons flow down the electron transport chain from negative to more positive redox potential.
Big jumps in redox potential equate to big changes in delta G.
These changes in free energy can be harnessed.
125
Outline the essence of phosphorylation.
High energy electrons (carried by NADH and FADH2 are used to reduce O2 to H2O.
Their energy is used to pump protons (H+) from the mitochondrial matrix to the intermembrane space.
Protons flow back across the membrane, following their concentration gradient.
Energy of proton flow is used to phosphorylate ADP to ATP.
This is a way to store energy temporarily.
126
Oxidative phosphorylation couples _ to __.
Respiration
ATP Synthesis
127
The two stages of oxidative phosphorylation
- electron transport outline
Electrons flow from NADH and FADH2 to O2.
Respiratory chain.
Energy is used to pump H+ out of the mitochondrial matrix.
128
The two stages of oxidative phosphorylation
- ATP Synthesis outline
Electrochemical gradient of H+ across the mitochondrial inner membrane.
Energy stored in this gradient can be used to synthesized ATP.
129
Electron transport and ATP synthesis are catalysed by ____ proton pumps.
Separate
130
Steps in the respiratory chain of electron transport.
A series of four protein complexes that couple redox reactions, creating an electrochemical gradient that leads to the creation of ATP in a complete system called oxidative phosphorylation.
Electrons from NADH enter at complex 1.
Electrons from FADH2 enter at complex 2.
Electrons are handed down from higher to lower redox potentials, a thermodynamically favoured direction.
Electrons are ultimately transferred onto O2 to form H2O.
Ubiquinone (coenzyme Q, hydrophobic) shuttles rapidly within membrane.
131
Draw the simplified diagram of the respiratory chain.
[see notes for answer]
132
In the respiratory chain in the mitochondrion there are three complexes which are linked in series.
Describe NADH dehydrogenase complex.
The NADH dehydrogenase complex (typically called Complex I) is the largest of these respiratory enzyme complexes. It accepts electrons from NADH and passes them through a flavin mononucleotide and eight iron–sulphur clusters to ubiquinone. The reduced ubiquinol then transfers its electrons to cytochrome c reductase.
133
In the respiratory chain in the mitochondrion there are three complexes which are linked in a series.
Describe cytochrome C reductase.
The cytochrome c reductase (also called the cytochrome b-c1 complex and typically called Complex III) is a large membrane protein assembly that functions as a dimer. Each monomer contains three cytochrome hemes and an iron–sulphur cluster. The complex accepts electrons from ubiquinol and passes them on to the small, soluble protein cytochrome c, which is located in the crista space and carries electrons one at a time to cytochrome c oxidase.
134
In the respiratory chain in the mitochondrion there are three complexes which are linked in a series.
Describe cytochrome C oxidase.
The cytochrome c oxidase complex (typically called Complex IV) contains two cytochrome hemes and three copper atoms. The complex accepts electrons one at a time from cytochrome c and passes them to molecular oxygen. In total, four electrons and four protons are needed to convert one molecule of oxygen to water.
135
Outline the electrochemical gradient in the respiratory chain.
More protons in the intermembrane space than in the matrix.
Forms an electrical field with the matrix side being more negative.
Protons 'want' to flow back into the matrix.
This flow back into the matrix is coupled to ATP synthesis.
Electron transport is energetically favourable.
Generates a membrane potential - difference in voltage/charge (large force).
Generates a concentration gradient - difference in pH (smaller force).
136
Outline the structure and mechanism or ATP synthase.
Also called mitochondrial ATPase or F1F0ATPase.
F1 subunit protrudes into mitochondrial matrix.
F0 subunit is a hydrophobic complex in the inner membrane, contains the proton channel.
a, b, [alpha], [beta] and [delta] subunits form the stator.
c, [gamma] and [epsilon] subunits form the rotor.
Flow of protons turns the rotor.
Conformational changes in the stator caused by the rotor turning leads to ATP synthesis.
137
Draw and label a diagram of ATP synthase.
[see notes for answer]
138
Outline the P/O ratio.
A measurement of the coupling of ATP synthesis to electron transport.
Number of molecules or inorganic phosphate (Pi) and depends on which substrate is oxidised:
- if NADH is oxidised to NAD+, P/O ratio = 2.5
- if FADH2 is oxidised to FAD, P/O ratio = 1.5
139
Outline OXPHOS diseases.
Involve components of oxidative phosphorylation.
Common degenerative diseases.
Mutations in mitochondrial or nuclear DNA.
Pathology, usually becomes worse with age
- Initially, a decreasing number of normal mitochondria may provide enough ATP
- With age, spontaneous mutations accumulate
- At some point not enough ATP can be generated
Symptoms usually appear in tissues with highest ATP demands.
- Nervous system, heart, skeletal muscle, kidney
140
Describe Uncoupling of the electron transport chain and ATP synthesis.
Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit ATP synthesis without affecting the respiratory chain and ATP synthase (H(+)-ATPase).
141
Define Glycogenesis.
Synthesis of glycogen from glucose.
142
Define Glycogenolysis.
Breakdown of glycogen to form glucose.
143
Outline the function of Glycogen.
Main storage form of glucose in liver and muscle cells.
Liver glycogen: broken down between meals and released to maintain blood glucose for red blood cells and the brain.
Muscle glycogen: not available for maintenance of blood glucose levels, provides energy during bursts of physical activity.
144
_____ fluctuates dependent on meal times. _______ is the primary source of glucose overnight when hepatic glycogen is depleted.
Glycogenolysis
Gluconeogenesis
145
_____ is a polymer of glucose molecules joined together by [alpha]-1,-glycosidic links. ____ are introduced by [alpha]-1,6-glycosidic links.
Glycogen
Branches
146
Outline the growth of glycogen chains.
Glucose residues can only be added to an existing glycogen chain.
UDP-glucose acts as an intermediate.
Requires a glycogen 'primer' containing at least 4 glucose residues.
The primer is covalently attached to a protein called glycogenin.
147
Draw the pathway of Glycogen synthesis.
[see notes for answer]
148
Outline UDP-glucose.
Simple precursors are first converted to activated intermediates (a common feature of biosynthetic pathways).
UDP-glucose can be thought of as an 'activated' form of glucose (ATP and acetyl-CoA are activated forms of phosphate and acetate).
The phosphate ester linkage in a nucleotide sugar releases free energy on hydrolysis.
149
Formation reaction of UDP-glucose.
UTP + glucose-1-P -> UDP-glucose + pyrophosphate (PPi)
150
Describe the reaction of UDP-glucose formation.
UDP-glucose and pyrophosphorylase catalyses this reaction.
This reaction is reversible however, there is a very active pyrophosphatase in cells which hydrolyses PPi and 'pulls' the reaction in favour of UDP-glucose synthesis.
151
Define rate limiting enzyme.
Slowest enzyme in a chain of reactions or one that is regulated.
152
Outline glycogen synthase.
Synthesises glycogen from UDP-glucose (the rate limiting enzyme).
Adds one glucose molecule to glycogen at a time.
Can only extend the chains of glycogen, cannot introduce branches.
Can not start a new molecule.
Branching enzyme, a transglycosylase, introduces [alpha]-1,6-glycosidic branches into glycogen approximately every 10 glucose branches.
153
Describe changes in Glycogenesis.
Glycogenesis occurs during and immediately after meals, when blood glucose is increased. Control is exerted on glycogen synthase activity.
Hyperglycaemia
- hormone and source: insulin, pancreatic [beta] cells
- effect: activation
Hypoglycaemia
- hormone and source: glucagon, pancreatic [alpha] cells
- effect: inactivation
154
Outline glycogenolysis.
Catalysed by glycogen phosphorylase.
One molecule of glucose is cleaved of the ends of glycogen at a time.
Glucose-1-phosphate is then converted to glucose-6-phospahte which can then go onto glycolysis.
In the liver
- glucose-6-phosphate can be dephosphorylated by glucose-6-phosphatase and the resulting glucose is released into the bloodstream.
In the skeletal muscle
- glucose-6-phosphate cannot be dephosphorylated but instead is used to provide energy via glycolysis and the TCA cycle.
Debranching requires additional enzymes.
155
Draw the pathway of glycogen breakdown.
[see notes for answer]
156
Describe the Hormonal control of glycogenolysis.
Hypoglycaemia
- hormone and source: glucagon, pancreatic [alpha] cells
- effect: activation
Stress + Hypoglycaemia
- hormone and source: adrenaline, adrenal medulla
- effect: activation
Stress
- hormone and source: cortisol, adrenal cortex
- effect: activation
Hyperglycaemia
- hormone and source: insulin, pancreatic [beta] cells
- effect: inactivation
All of this is dependent on demand for blood glucose, control is exerted on glycogen phosphorylase activity.
157
Outline reciprocal regulation.
Hormonal regulation
-Glucagon -> has a negative effect on phosphofructokinase but a positive effect on fructose 1,6 – bisphosphatase.
-Insulin -> has a positive effect on phosphofructokinase but a negative effect on fructose 1,6 – bisphosphatase.
High AMP or ADP means low energy.
Fructose 2,6 – bisphosphate is high in the fed state and low in the starved state.
Citrate, alanine and acetyl-CoA are high when intermediates or building blocks are abundant.
158
Draw the summary diagram of glycogenesis and glycogenolysis.
[see notes for answer]
159
Outline gluconeogenesis.
Synthesis of glucose within the body from non-carbohydrate precursors.
During prolonged starvation, new glucose has to be synthesised.
Precursors:
- Lactate: synthesised by skeletal muscle under anaerobic conditions.
- Amino acids: derived from muscle protein by proteolysis.
- Glycerol: derived from triglycerides by lipolysis in adipose tissue.
Energy
From oxidation of fatty acids released from adipose tissue.
Location
Mainly in the live, small amounts in the kidneys. Gluconeogenesis is essentially the reverse of glycolysis.
160
Draw the diagram of the gluconeogenesis pathway.
[see notes for answer]
161
Four unique enzymes are required for gluconeogenesis. Describe Pyruvate carboxylase.
Pyruvate carboxylase (PC)
coverts pyruvate to oxaloacetate.
162
Four unique enzymes are required for gluconeogenesis. Describe phosphoenolpyruvate carboxykinase.
Phosphoenolpyruvate carboxykinase (PEPCK)
A rate limiting enzyme that converts oxaloacetate to phosphoenolpyruvate.
163
Four unique enzymes are required for gluconeogenesis. Describe Fructose-1,6-bisphophatase.
Fructose-1,6-bisphosphatase (FBPase)
Coverts fructose-1,6-phosphate to fructose-6-phosphate.
164
Four enzymes are required for gluconeogenesis. Describe glucose-6-phosphatase.
Glucose-6-phosphatase (G6Pase)
Converts glucose-6-phosphate to glucose.
165
Define 'anaplerotic reaction'
Important reactions for accepting acetyl groups from fat breakdown.
166
Gluconeogenesis is important especially in the absence of ____________ because it allows the body to still produce new _____ and maintain stable blood _________.
Dietary carbohydrates
Glucose
Glucose levels
167
Draw a diagram of the Cori Cycle
[see notes for answer]
168
Outline the cori cycle.
Lactate as a precursor of gluconeogenesis (formed in fast-twitch) muscle under conditions of heavy exercise.
Blood transports lactate to the liver.
Liver converts lactate back to glucose.
Glucose is released into the bloodstream.
Buys time and shifts metabolic burden from the muscle to other organs.
169
Draw a diagram of amino acids acting as precursors in the TCA cycle.
[see notes for answer]
170
Why are amino acids degraded?
Amino acids which are not used as building blocks are degraded as there is no storage for amino acids, the liver is the main site of amino acid degradation.
171
Describe the absorption of amino acids.
Proteolytic enzymes in the stomach and intestine produce single amino acids and di- and tri- peptides. These are absorbed into intestinal tissue cells and released into blood for absorption by other tissues.
172
Describe protein turnover of amino acids.
Is tightly regulated and takes place at different rates which is important for rapid changes. Damaged proteins have to be removed.
173
Describe the problems of amino acid degradation.
Some amino acids contain nitrogen in their side chains, amino acid breakdown of these produces ammonia (NH3) and ammonium ions (NH4+). NH4+ is toxic at high levels and build up leads to severe problems so we need a safe way of excreting nitrogen.
174
Define ketogenic amino acids.
Degraded to acetyl-CoA or acetoacetyl-CoA.
Cn give rise to ketone bodies of fatty acids.
175
Define glucogenic amino acids.
Degraded to pyruvate or TCA cycle intermediates.
Can be converted into phosphoenolpyruvate and then into glucose.
176
Describe inherited disorders and amino acid degradation.
Alcaptonuria:
- degradation of phenylalanine and tyrosine is blocked
Maple syrup urine disease:
- degradation of valine, isoleucine, and leucine is blocked
- urine smells like maple syrup
- mental and physical retardation
- prevented by appropriate diet
Phenylketonuria:
- phenylalanine accumulates in all body fluids
- leads to severe mental retardation if untreated
- therapy: low phenylalanine diet
177
Describe fat and lipid metabolism.
Increased fat intake without appropriate energy expenditure leads to an increased number of adipocytes and more fat in adipocytes. Also obesity.
Control of energy balance depends on;
- Genetically linked factors such as protein messengers regulating appetite.
- Environmental factors such as food abundance, and fashionable foods.
178
Describe body max index (BMI)
Is the measurement of obesity.
Calculated by weight/(height)^2
However does not take into account muscle mass and bone density.
179
Outline medical complications of obesity.
Diabetes mellitus (80% associated with obesity).
Coronary heart disease.
Hypertension.
Stroke
Arthritis
Gall bladder disease
180
Describe why fat metabolism is needed.
However fat is also required for energy as it is the highest source of energy found in the body.
It is also necessary for essential fatty acids as some of them cannot be made by the body such as linoleic acid and arachidonic acid. Deficiencies in these fatty acids can lead to membrane disorders, increased skin permeability and mitochondrial damage.
Also is vital for fat-soluble vitamins such as vitamins A, D, E and K as absorption of these are closely linked to that of fat and they are stored in body fat.
If fat intake or absorption is inadequate secondary deficiencies can occur.
181
Outline steroids.
Don't usually contain fatty acids.
Occur in natural fats.
Cholesterol - rigid structure, multiple rings, found in cell membranes.
Adrenocortical and sex hormones - derived from cholesterol.
182
\Describe triglycerides.
Are the main energy storage form in adipose tissue. They are compact and don’t require concomitant storage of water. They are hydrophobic and have a high energy yield per gram.
183
Describe fatty acids.
Are mainly straight chains, they do not contain any rings and are therefore aliphatic. They usually have an even number of carbon atoms, branched chains and odd numbers of carbon atoms are rare.
They can be:
- Saturated (no double bonds)
- Unsaturated (one double bond)
- Polyunsaturated (several double bonds)
The double bonds are usually in cis configuration.
184
Describe fat absorption.
The main products of fat digestion:
- Glycerol (readily absorbed in intestinal epithelial cells)
- Fatty acids
- Monoglycerides
Fats are absorbed into mucosal cells of the intestine, short and medium length fatty acids enter portal blood whereas longer chain fatty acids and monoglycerides are resynthesized to triglycerides.
Coated with a layer of protein, phospholipid, cholesterol; Chylomicrons.
185
Draw a diagram describing the pathway of chylomicrons.
[see notes for answer]
186
Describe chylomicrons.
Enter the lymph and then the blood.
At muscle and adipose tissue, chylomicrons are attacked and cleaved by lipoprotein lipases.
There free fatty acids are:
- Resynthesized into triglycerides (in adipose tissue, for storage)
- Oxidised to provide energy (in muscle)
- Depends on amount available
187
Describe the lipolysis of fat.
Lipolysis = breakdown of lipids. Fat is stored in adipose tissue.
Initial cleavage by hormone sensitive lipases (e.g. adrenaline sensitive), this releases free fatty acids and glycerol and occurs when energy is needed.
188
Describe the activation of fatty acid oxidation.
Before fatty acids can be oxidised to generate energy, they have to be converted to coenzyme a derivatives. This occurs in the cytoplasm and requires energy. But further oxidation of fatty acids occurs in the mitochondrial matrix, they need to be transported into mitochondrial by special carrier mechanism.
189
Describe the carnitine shuttle.
In the cytoplasm, fatty acids are transferred from acetyl-coenzyme A to carnitine. Acetyl-carnitine transporter in inner membrane facilitates antiport of acetyl-carnitine into the mitochondrion and carnitine out.
This is important for regulation of fatty acid oxidation, net result; acetyl-coenzyme A located in mitochondrial matrix.
190
Draw a diagram of the carnitine shuttle.
[see notes for answer]
191
Describe beta oxidation.
A cycle of reactions in mitochondrial matrix, four steps in each cycle. Products of each cycle:
* 1 acetyl-CoA
* 1 FADH2
* 1 NADH + H+
* 1 fatty acetyl-CoA, shortened by 2 carbon atoms
The main yield of beta oxidation is stearic acid (C18).
The cycle is repeated 8 times, which creates –
8 FADH2, 8 NADH + 8 H+ which is used for ATP generation in oxidative phosphorylation.
9 acetyl-CoA can be oxidised in the TCA cycle to CO2 yields 9 FADH2, 7 NADH + 27 H+, 9 GTP.
Total yield = 17x1.5 + 35x2.5 + 9 – 2 = 120 ATP
192
Describe the breakdown of glycerol.
Activated to glycerol-3-phosphate by glycerol kinase which is present in the liver and kidney but are absent from adipose tissue, skeletal and heart muscle.
Dehydrogenated to dihydroxyacetone phosphate a normal intermediate of carbohydrate metabolism.
193
Describe lipogenesis (fatty acid synthesis).
Synthesis of fatty acids occurs mainly in liver, kidney, mammary glands, adipose tissue and brain. Mainly takes place during excess energy intake.
When excess carbohydrate is taken in:
- Conversion to fatty acids and triglycerides in the liver
- Free fatty acids are transported in plasma bound to albumin
- Triglycerides formed in the liver are transported to adipose tissue by VLDL for storage (a very low density lipoprotein)
Lipogenesis is a reductive process, electrons are required.
194
Draw the pathway of lipogenesis.
[see notes for answer]
195
Describe blood glucose levels after eating.
Post prandial (after food); ongoing digestion, most abundant energy sources, blood glucose levels rise directly due to food source.
196
Describe blood glucose levels after digestion is complete.
Post absorptive (after digestion is complete); at least 3-5 hours after meal typically overnight, blood glucose maintained by liver glycogen.
197
Describe the blood glucose levels after a prolonged period of fasting.
Fasted state (prolonged period of fasting); at least 12 hours in many cases 72 hours or more, glycogen depleted utilisation of alternate energy sources.
198
Draw a diagram of postprandial metabolism.
[see notes for answer]
199
Draw a diagram for postabsorptive metabolism.
[see notes for answer]
200
Draw a diagram for prolonged fasting.
[see notes for answer]
