Metabolism

Question 1

What is metabolism?

Answer 1

The sum of all the chemical processes necessary to make possible the characteristic of living cells/organisms.

Question 2

What is the difference between phototrophs, chemotrophs, heterotrophs and autotrophs?

Answer 2

Phototrophs → use light for energy

Chemotrophs → use compounds for energy, either organic or inorganic

Heterotrophs → use an organic source of carbon and reducing power

Autotrophs →​ use an inorganic source of carbon and reducing power

Question 3

What is the difference between catabolism and anabolism?

Answer 3

Catabolism (fuel oxidation) → breaking down complex compounds into simpler ones; oxidative reactions that release energy and can occur spontaneously.

Anabolism (biosynthesis) → synthesising more complex compounds from simpler ones; reduction reactions the require energy and do not occur spontaneously.

Question 4

What are the important needs metabolic regulation must meet, regardless of the situation the body is in?

Answer 4

All cells need adequate metabolic fuel

All cells need the correct form of fuel (eg. the brain requires glucose)

Blood glucose must be kept within a set range

Waste products (eg. Nitrogen) must be removed safely

Excess fuel should be stored, not wasted

Question 5

Which fuels do the important metabolic organs use, and what are their functions?

Answer 5

Brain → uses glucose exclusively as a fuel, but also uses ketone bodies during starvation

Skeletal muscle → When glucose is plentiful, it stores glycogen for its own use

Liver → when glucose is plentiful, it makes glycogen and fat. Releases fuel during fasting and exercise.

Adipose tissue → When fat is plentiful, stores fat. Releases fat during exercise and fasting.

Question 6

What are the 3 different metabolic states?

Answer 6

Fed → body is currently digesting food. Liver will use excess fuel to make glycogen and fat. Tissues will take up excess glucose. Adipose tissue will take up and store excess fat.

Fasting → Liver releases glucose and ketone bodies. Adipose tissue releases fat. Most tissues switch to fat use.

Exercise → Muscle fuel use increases. Adipose tissue releases fats. Liver releases glucose.

Question 7

What are the different sources of glucose in different metabolic states?

Answer 7

Fed → glucose from small intestine due to digestion

Fasting → No glucose in small intestine so glycogen is released from the liver

Exercise → Muscles need lots of ATP so they use muscle glycogen

Starvation → no liver glycogen is left, so other non-carbohydrates are used in gluconeogenesis.

Question 8

How is glycogen broken down?

Answer 8

1 → Glycogen phosphorylase uses free phosphate in solution to break the glycosidic bond and phosphorylate each product, forming 2 x glucose-1-phosphate.

2 → Phosphoglucomutase then moves the phosphate group, forming glucose-6-phosphate.

Question 9

What are the steps in the energy investment stage of glycolysis?

Answer 9

1 → glucose is phosphorylated by hexokinase into glucose-6-phosphate. ATP hydrolysis drives this reaction forward, and this step is regulated.

2 → G-6-P is isomerised into fructose-6-phosphate by glucose phosphate isomerase, as this makes C1 easier to phosphorylate in the next step.

3 → F-6-P is phosphorylated by phosphofructokinase, forming fructose-1,6-bisphosphate. ATP hydrolysis also drives this step forward, and this the most important regulatory step. The enzyme is regulated allosterically by ATP inhibition.

Question 10

How is 3-phosphoglycerate formed from fructose-1,6-bisphosphate in glycolysis?

Answer 10

1 → Aldolase splits F-1,6-BP into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (DHAP).

2 → DHAP is isomerised into G-3-P by triosephosphate isomerase, allowing both halves of the glucose molecules to be used.

3 → G-3-P is oxidised by G-3-P dehydrogenase, reducing NAD⁺ to NADH in the process. There is enough energy left over to attach one inorganic phosphate ion to form 1,3-bisphosphoglycerate.

4 → Phosphoglyceratekinase transfers one phosphate group from 1,3-BPG to ADP, forming ATP (via substrate level phosphorylation) and 3-phosphoglycerate.

Question 11

How is pyruvate formed from 3-phosphoglycerate in glycolysis?

Answer 11

1 → Phosphoglycerate kinase moves the phosphate group from C1 to C2 on 3-phosphoglycerate, forming 2-phosphoglycerate. This moves the phosphate into a less stable position.

2 → Enolase dehydrates 2-PG, forming phosphoenolpyruvate. The phosphate is now in an even less stable position.

3 → Pyruvate kinase removes the phosphate group, forming enol-pyruvate; because the phosphate was in a very unstable position, this reaction also drives forward the substrate level phosphorylation of ADP. This enzyme is regulated because the reaction is highly exothermic.

4 → Enol-pyruvate spontaneously breaks down into pyruvate, meaning that this last step is not reversible.​

Question 12

How is NADH converted back into NAD⁺?

Answer 12

Glycolysis occurs in the cytosol, and the mitochondria can use O₂ to convert NADH back into NAD+. Therefore, this process in aerobic.

Lactate fermentation → Lactate dehydrogenase drives the reduction of pyruvate into lactate, thereby oxidising NADH into NAD^+.

All tissues in humans produce lactate, especially RBCs (no mitochondria) and exercising white muscle. The liver takes up lactate and uses it to produce glucose via gluconeogenesis, which requires energy.

Alcoholic fermentation → Pyruvate is decarboxylated by pyruvate decarboxylase, forming ethanal. This is then reduced by alcohol dehydrogenase, oxidising NADH to NAD⁺. This process occurs in yeast.

Question 13

What is the yield of glycolysis?

Answer 13

Glycogen → 2x NADH, 2x pyruvate and 3x ATP (due to being converted into G-1-P without using up ATP)

All other sugars → 2x NADH, 2x pyruvate, 2x ATP

Question 14

What happens to glycolysis in the fed state?

Answer 14

Brain → only can use glucose for fuel, so the rate of glycolysis stay the same.

Liver → First organ to receive glucose (due to blood vessel connecting it to the small intestine). Glycolysis increases, glycogenesis increases, and fat synthesis increases.

Adipose tissue → Glucose is taken up and broken down for fat synthesis.

Skeletal muscle → Glycolysis increases while fatty acid oxidation decreases.

Question 15

What happens to glycolysis during exercise?

Answer 15

Brain → only uses glucose for fuel, so rate of glycolysis doesn’t change

Liver → Glycogen breakdown is stimulated, producing glucose which is released into the blood.

Skeletal muscle → Glucose is taken up from the blood and glycogen stores are broken down. Glycolysis increases, and lactate may be produced with intense exercise.

Question 16

What happens to glycolysis during fasting?

Answer 16

Brain → only uses glucose for fuel, so rate of glycolysis doesn’t change

Liver → Glycogen is broken down and gluconeogenesis occurs in order to try and keep the blood glucose level constant.

Adipose tissue → Fats are broken down and the products are released into the blood so that tissues have an alternative fuel source to glucose.

Skeletal muscle → Glycolysis is inhibited and fats are used. Amino acids are also released into the blood

Question 17

What happens to glycolysis during starvation?

Answer 17

Brain → Tries to use less glucose by using ketone bodies

Liver → Glycogen stores have run out. Some gluconeogenesis and ketone body formation occurs.

Kidneys → Gluconeogenesis helps to maintain glucose level

Adipose tissue → Fats are broken down and released into the blood to provide an alternative fuel source to glucose

Skeletal muscle → Glycolysis is inhibited and fats are broken down. Amino acids are released into the blood.

Question 18

What is the most important form of fat storage, and why is it so important?

Answer 18

Triacylglycerol accounts for around 85% of fat stored in the body.

It is very efficient at storing fat, and stores much more energy than glycogen by both weight and volume.

Question 19

What are the different sources of fat?

Answer 19

Liver → During the fed state, the liver can make and release fats in the form of lipoproteins, which are then taken up by adipose tissue

Blood → Free fatty acids bound to albumin circulate in the plasma (due to slightly soluble COO^-). Can also circulate as triacylglycerol packaged in lipid membranes, cholesterol and protein ie. as lipoproteins. This prevents them clumping together and blocking blood vessels due to being hydrophobic.

Adipose tissue → The main site of fat storage

Skeletal muscle → Some types of muscle fibres contain fat droplets

Question 20

What is the difference in function of hormone-sensitive lipase and lipoprotein lipase?

Answer 20

HSL → Acts on triacylglycerol in intracellular lipid droplets. The fatty acid is then released into the blood and another part of the tissue can take it up and use it as fuel. It is stimulated by exercise (adrenaline), the cold (noradrenaline) and fasting (low insulin).

LPL → Acts on triacylglycerol in lipoproteins circulating in the blood. LPL is attached to the capillary wall, catalyses the reaction when a lipoprotein passes, and then the fatty acid enters a tissue that needs it. The cell that secretes LPL may not receive all of the fatty acids that are released - it may not receive any of it either.

Question 21

In which situations would adipose tissue and skeletal muscle secrete hormone-sensitive lipase and lipoprotein lipase?

Answer 21

Adipose + HSL → Adipose tissue wants to release fatty acids into the blood because another part of the body needs it as fuel.

Muscle + HSL → Muscle tissue wants to use the fatty acids as fuel

Adipose + LPL → Adipose tissue wants to take up fatty acids and store them

Muscle + LPL → Muscle tissue wants to use fatty acids as fuel

Question 22

Why must fatty acids be esterified with CoASH?

Answer 22

Because fatty acids are hydrophobic, they can diffuse through the cellular membrane and into mitochondria, or travel via transporters.

This is bad because fatty acids are toxic, as they can dissolve other hydrophobic compounds and cause damage.

To trap fatty acids inside the cell and outside of mitochondria, they are esterified with CoASH to form Coenzyme A, CoA.

This forms a thioester bond and uses up 2 x ATP with the reaction, making it irreversible:

ATP → AMP + PPi

Question 23

What are the steps involved in fatty acid (β) oxidation?

Answer 23

1 → Reduction

The fatty acyl-CoA is oxidised by fatty acyl-CoA dehydrogenase forming enoyl-CoA, reducing FAD to FADH₂ in the process. This forms a double bond between the α and β carbons.

2 → Hydration

The double bond is hydrated using the enzyme enoyl-CoA hydrolase, forming hydroxy acyl-CoA. This adds an hydroxyl group onto the β carbon.

3 → Reduction

The hydroxy acyl-CoA is oxidised by hydroxy acyl-CoA dehydrogenase, reducing NAD to NADH in the process. This forms a double bond on the β carbon, meaning the α-β bond is weak enough to be cleaved in the next step.

4 → Cleavage (thiolysis)

The α-β bond is cleaved by thiolase, and this joins with CoASH to form acetyl-CoA. The fatty acid is now 2 carbons shorter.

This process repeats until there are only 2 Cs left, and these can be joined directly onto CoASH.

Question 24

What are the equations for working out the number of acetyl CoAs and FADH₂ + NADH produced in fatty acid oxidation?

Answer 24

acetyl CoA = number of carbons in FA / 2

FADH₂​/NADH = ( number of carbons in FA / 2 ) - 1

Question 25

What happens to fatty acid oxidation during the fed state?

Answer 25

Brain → Neurons in the brain contain very low levels of thiolase, so they do not oxidise fatty acids. The brain will continue to use glucose as a fuel source.

Liver → Fatty acid oxidation is inhibited due to the increase in glycolysis and fatty acid synthesis.

Adipose tissue → Does not perform much FA oxidation, so no fatty acids are released into the blood.

Skeletal muscle → Fatty acid oxidation is inhibited due to glycolysis.

Question 26

What happens to fatty acid oxidation during exercise?

Answer 26

Brain → only uses glucose for fuel

Adipose tissue → Releases fatty acids into the blood

Skeletal muscle → Increased FA oxidation due to increased FA supply (from adipose tissue releasing them)

Question 27

What happens to fatty acid oxidation during fasting?

Answer 27

Brain → only uses glucose as fuel

Adipose tissue → Releases fatty acids into the blood

Skeletal muscle → Glycolysis is inhibited, so fatty acid oxidation increases

Question 28

What happens to fatty acid oxidation during starvation?

Answer 28

Brain → Uses glucose as well as ketone bodies for fuel; the glucose that is used up is replaced by protein breakdown

Adipose tissue → Releases fatty acids into the blood

Skeletal muscle → Glycolysis is inhibited, so fatty acid or ketone bodies are used as fuel.

Question 29

What are ketone bodies and how are they made?

Answer 29

Ketone bodies are made by the liver and can be used as an alternative fuel source, specifically by the brain during starvation.

2x Acetyl CoA → 2x CoASH + 4C ketone body

Cells only require aerobic conditions and mitochondria in order to use ketone bodies as a fuel, so most tissues can use them.

Question 30

What happens in the Link reaction, and why is it important?

Answer 30

Pyruvate in the cytosol enters the mitochondria and is converted into acyl-CoA by pyruvate dehydrogenase.

The Link reaction is important because it ‘links’ anaerobic glycolysis to aerobic metabolism in mitochondria.

Pyruvate + CoASH + NAD → Acetyl CoA + CO₂ + NADH

This reaction is very exothermic and so it is regulated, but it is absolutely irreversible; there are no enzymes in the human body that can convert acetyl-CoA back into pyruvate.

Question 31

How is isocitrate formed from oxaloacetate in the citric acid cycle?

Answer 31

1 → Acetyl-CoA and oxaloacetate react to form citrate, and this is catalysed by citrate synthase. Hydrolysis of the thioester bond provides the energy to form a C-C bond. This reaction has a very -ΔG, so the enzyme is regulated.

2 → Citrate is isomerised into isocitrate by aconitase; aconitase moves the hydroxyl group from C3 to C2 in order to make the COO- group easier to decarboxylate in the next step. This reaction has a very +ΔG, so it is compensated and driven forward by the previous reaction and the abundance of citrate.

Question 32

How is isocitrate converted into succinate in the citric acid cycle?

Answer 32

1 → Isocitrate undergoes oxidative decarboxylation to form alpha-ketoglutarate, aided by the enzyme isocitrate dehydrogenase. This reduces NAD to NADH and forms CO₂. This reaction has a very -ΔG, so the enzyme is regulated.

2 → Alpha-ketoglutarate undergoes oxidative decarboxylation, forming succinyl-CoA with the help of the enzyme alpha-ketoglutarate dehydrogenase. This reduces NAD into NADH and forms another CO₂. This reaction also has a very -ΔG, so this enzyme is regulated (and is the last one in the cycle to be regulated).

3 → Succinyl-CoA is converted into succinate via succinyl-CoA synthetase. The hydrolysis of the thioester bonds provides the energy to phosphorylate ADP/GDP, forming ATP/GTP via substrate level phosphorylation. This reaction is reversible within the cell.

Question 33

How is succinate turned back into oxaloacetate in the citric acid cycle?

Answer 33

1 → Succinate is oxidised into fumarate using the enzyme succinate dehydrogenase. This reduces FAD into FADH₂ in the process. This forms a double bond between C2 and C3. ΔG = 0

2 → The double bond in fumarate is hydrated to form malate, which has a hydroxyl group on C2. The enzyme that catalyses this reaction is fumarase, and ΔG = -3.8

3 → Malate is oxidised into oxaloacetate using the enzyme malate dehydrogenase, which forms a C=O on C2. This also reduces NAD into NADH. This reaction has a very +ΔG, but it is compensated by the following reaction having a very -ΔG, as well as the fact that oxaloacetate is constantly being removed.

Question 34

What is the yield of the citric acid cycle?

Answer 34

1 x CoASH

2 x CO₂

3 x NADH = 7.5 ATP

1 x FADH₂ = 1.5 ATP

10 ATP in total

Question 35

What happens to the citric acid cycle in each metabolic state?

Answer 35

Fed → Glycolysis is increased, so acetyl-CoA comes from sugars

Fasting → Glycolysis is inhibited, so acetyl-CoA comes from fatty acid oxidation

Exercise → The citric acid cycle enzymes are stimulated, and acetyl-CoA supply is increased due to both increased glycolysis and fatty acid oxidation. The concentration of intermediates also increases.

Question 36

How are amino acids catabolized in different tissues?

Answer 36

Skeletal muscle → Uses amino acids as a fuel particularly branched chain amino acids like Ile, Leu, Val.

Liver → Uses amino acids as a fuel, especially as it is the only organ that can synthesise urea.

Small intestine → Uses amino acids from digestion and from the blood as a fuel.

Question 37

How can the amino group be removed from useful amino acids?

Answer 37

The amino group is transferred onto a small carbon compound using the enzyme aminotransferase. This forms a simple amino acid (eg. Ala, Glu, Gln) plus an alpha-ketoacid that can be used in the citric acid cycle.

Alanine + alpha-ketoglutarate → Pyruvate + Glutamate

Glutamate → alpha-ketoglutarate (NH₂ not transferred to another compound)

Leucine → 3 x acetyl-CoA

Question 38

What happens to amino acid catabolism in the fed state?

Answer 38

Skeletal muscle → Takes up branched amino acids and uses them for fuel

Brain → only uses glucose for fuel

Liver → uses amino acids for fuel, but may also use them to synthesise glucose or fats.

Small intestine → uses amino acids from digestion and circulation as fuel, especially Glutamine

Question 39

What happens to amino acid catabolism during starvation?

Answer 39

Brain → uses glucose and keto acids as fuel

Liver → May use amino acids to synthesise glucose or keto acids, and the ones that can’t be converted are used as fuel

Small intestine → Uses amino acids from circulation, especially Glutamine

Skeletal muscle → Oxidises amino acids instead of glucose, and releases amino acids into the blood.