Biochemistry L11/12/13 - Metabolism

Question 1

What is anabolism and what is catabolism?

Answer 1

Anabolism – to build up. It’s the synthesis of complex molecules in living organisms from simpler ones together with the storage of energy; constructive metabolism.

Catabolism – to break down - the breakdown of complex molecules in living organisms to form simpler ones, together with the release of energy; destructive metabolism.

Question 2

What can cause variations and adaptations in NORMAL metabolism?

Answer 2

• starvation
• exercise
• pregnancy
• lactation

Question 3

What can cause abnormal metabolism?

Answer 3

• nutritional deficiency
• enzyme deficiency
• abnormal secretion of hormones (i.e. diabetes mellitus)

Question 4

What are the main metabolic fuels?

Answer 4

Glucose and fats (fatty acids and glycerol), but proteins can also be used.

Question 5

What are metabolic pathways comprised of?

Answer 5

Enzyme catalyzed reactions usually linked in a series or arrays.

Question 6

Where does glycolysis occur?

Answer 6

Cytosol

Question 7

What are the potential products of glycolysis in humans?

Answer 7

• Pyruvate (aerobic conditions)

- Lactate (anaerobic conditions)

Question 8

What is the molecular formula for glucose?

Answer 8

C(6)H(12)O(6)

Question 9

Name the enzymes used in the 3 main points of regulation of glycolysis. Note: these reactions only proceed in the forward direction.

Answer 9

Hexokinase
Reaction: glucose –> glucose 6-phosphate (the first ‘priming reaction’).
A phosphate group is added to glucose using ATP. This is the first step of glycolysis

Phosphofructokinase-1
Reaction: fructose 6-phosphate –> fructose 1,6-biphosphate (the second ‘priming reaction’).
A second phosphate group is added to glucose using ATP. This is the third step of glycolysis

Pyruvate Kinase
Reaction: Phosphoenolpyruvate –> pyruvate (2ADP are converted to 2ATP. It is the second ATP-forming reaction). This is the last step of glycolysis

Question 10

Why does the heart muscle survive poorly under conditions of ischemia?

Answer 10

Tissue can survive periods of anoxia because glycolysis can occur in the absence of oxygen. But heart muscle has relatively poor glycolytic ability, so it survives poorly without oxygen.

Question 11

Why does fermentation occur in the absence of oxygen?

Answer 11

Glucose will still react to form 2 pyruvate molecules, but NADH accumulates in the absence of oxygen and inhibits pyruvate oxidation. Instead, the pyruvate molecules will be converted to lactate (enzyme=lactate dehydrogenase) and will cause NAD+ regeneration.

Question 12

What are the muscle metabolic systems used during exercise?

Answer 12

Anaerobic Exercise:
- Stored ATP and Creatine-P. Lasts about 8-10 seconds during high intensity exercise.
- Anaerobic glycolysis, yielding about 1.3-1.6 minutes of maximal muscle activity.
Oxygen demand in the mitochondria of muscle cells will eventually exceed the capacity of the blood to deliver it.

Aerobic Exercise:
- Aerobic system – metabolic reactions taking place in the mitochondria. Occurs during lower intensity exercise. This can keep going until nutrients are depleted.

Question 13

What is the Cori cycle and why do we need it?

Answer 13

The lactic acid cycle that occurs in the liver. It refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate.

It’s important in preventing lactic acidosis – a low pH in body tissues and blood (acidosis) accompanied by the buildup of lactate. Lactic acidosis also occurs with a deficiency in the enzyme pyruvate dehydrogenase, as pyruvate cannot be turned into acetyl-CoA, and is predominantly transformed into lactic acid.

Question 14

How is the oxidation of pyruvate to Acetyl-CoA regulated, and which enzyme catalyses this reaction?

Answer 14

Relative concentrations of Pyruvate, Acetyl CoA, NADH and ADP regulate the oxidation of pyruvate.

The reaction is an irreversible reaction catalyzed by Pyruvate Dehydrogenase (PDH). PDH is inhibited by NADH, Acetyl CoA and ATP (the first are products of the oxidation of pyruvate to Acetyl CoA and the second is a product of the ETC).
PHD is activated by ADP and pyruvate.

Question 15

Which tissues depend predominantly on glycolysis for ATP and why?

Answer 15

Tissues with little or no mitochondria as pyruvate cannot enter the TCA cycle.

Examples: RBCs, cornea, lens, retina, kidney, medulla, testis, leukocytes and white muscle.

Question 16

What does one cycle of the TCA cycle produce and what is the TCA cycle regulated by?

Answer 16

• 3 NADH, 1 FADH2 and 1GTP. It also releases 2CO2.

- Upregulated by ADP, downregulated by ATP and NADH, as well as product down regulation.

Question 17

What is anoxia and hypoxia and what does it do to the TCA cycle?

Answer 17

Anoxia – complete lack of oxygen supply to tissue
Hypoxia – decreased supply of oxygen in tissue

They lead to total or partial inhibition of the TCA cycle, as it is aerobic.

Question 18

Why are NADH and FAHD2 important in the Electron Transport Chain (ETC)?

Answer 18

Electrons are transferred from NADH and FADH2 into the ETC and finally to O2 (the terminal electron receptor) to drive the formation of ATP.

Question 19

How much ATP does a molecule of NADH and a molecule of FADH2 produce?

Answer 19

NADH – 3ATP

FADH2 – 2ATP

Question 20

What happens to the carbon atoms in glucose after it has been completed metabolized?

Answer 20

They are exhaled as CO2.

Question 21

What drives phosphate and pyruvate import into the mitochondrial matrix?

Answer 21

Proton Gradient

Question 22

What process drives the oxidative phosphorylation of ATP?

Answer 22

Proton Gradient (also known as the electrochemical or voltage gradient).

Question 23

What is the overall equation of glucose oxidation?

Answer 23

(C6H12O6) + 6O2 + 38 ADP3- +38Pi2- +38H+

= 6CO2 + 6H2O + 38 ATP 4-

Question 24

What is gluconeogenesis?

Answer 24

Net synthesis or formation of glucose from various substates such as glucogenic amino acids, lactate, pyruvate, glycerol, galactose/fructose

Question 25

What THREE enzymes are used to bypass the irreversible reactions in glycolysis during gluconeogenesis?

Answer 25

1. Pyruvate carboxylase (pyruvate->oxaloacetate)
2. Fructose-1,6-bisphosphatase (fructose-1,6-biphosphate -> fructose 6 phosphate)
3. Glucose-6-phosphatase (glucose-6-phosphate -> glucose)

Question 26

Where does the ATP required for gluconeogenesis come from?

Answer 26

beta-oxidation of fatty acids

Question 27

What are the two PURELY ketogenic amino acids?

Answer 27

Leucine, Lysine - this is because they are converted into acetyl CoA, which cannot be converted back to pyruvate

Question 28

Can fatty acids be converted to glucose?

Answer 28

NO

Question 29

What is the process converting stored glycogen into glucose?

Answer 29

Glycogenolysis

Question 30

What are the two essential fatty acids?

Answer 30

linoleic (omega 6), linolenic (omega 3)

Question 31

In fatty acid synthesis, what is acetyl CoA initially converted into (commitment step)?

Answer 31

Malonyl CoA

Question 32

What are 4 factors influencing control of metabolic pathways?

Answer 32

1. Availability of substrates
2. Allosteric activation & inhibition of enzymes
3. Covalent modification of enzymes
4. Induction & repression of enzyme synthesis

Question 33

During starvation, what substrates does brain use for energy after glucose runs out?

Answer 33

Ketones

Question 34

What are some signs of diabetic ketoacidosis?

Answer 34

Hyperglycaemia, Kenonemia, Ketonuria

Question 35

What are glucogenic amino acids?

Answer 35

Amino acids that can be converted into glucose using carbon skeleton via gluconeogenesis

Question 36

Which molecule carries FA into the mitochondria?

Answer 36

Carnitine

Question 37

What products are produced by one round of beta oxidation in the mitochondria?

Answer 37

1 Acetyl CoA, 1FADH2 and 1NADH

Question 38

Why are triglycerides a more effective energy store than glycogen?

Answer 38

On a weight basis, TAG’s yield 2.5x more ATP than glycogen, and they can be stored without water association - glycogen binds about 2x it’s weight in water, so you need 3x the tissue weight of glycogen for energy, for the same fat weight.
Fat sources can also last the human body several weeks, while glycogen only lasts about one day

Question 39

What is the purpose of Urea?

Answer 39

Allows the body to carry ammonia/ammonium in a non-toxic state

Question 40

From which three pathway intermediates are amino acids synthesized?

Answer 40

Glycolytic pathway
Citric acid cycle
Pentose phosphate pathwat

Question 41

What are the basic metabolic changes in starvation?

Answer 41

• After fasting for a day, most glycogen has been used. The brain can only use glucose or ketones, but needs time to build up the enzymes to allow it to use ketones.
• As you fast, lipolysis is turned on to supply glucose and ketone bodies to the brain. TAGs are broken down into glycerol and FFA. FFA go to the liver to be converted into ketone bodies, glycerol is used in gluconeogenesis
• The ketone bodies generated in the liver go to both the brain, and the muscles, to be used for energy. This has a glucose sparing effect at the muscles, allowing any remaining glucose to be conserved for the brain.
• Skeletal muscle is also broken down (proteolysis) into amino acids, which are used for gluconeogenesis in the liver.
• Any glycogen stores in the body, and any glucose produced by breakdown of glycerol/amino acids, is spent to the brain.

Question 42

Which metabolic processes occur in the brain?

Answer 42

Glycolysis, Pentose Phosphate Pathway and the TCA cycle.
NO BETA-OXIDATION - the brain cannot use free fatty acids
NO GLUCONEOGENESIS - the brain is reliant on other organs to produce glucose/ketone bodies

Question 43

What happens in the Pentose Phosphate Pathway?

Answer 43

Its a metabolic pathway that runs parallel to glycolysis, and generates NADPH and pentoses (5-carbon sugars), as well as ribose-5-phosphate, which is a precursor for nucleotides.
Takes place in the cytosol