metabolism

Question 1

What are metabolic pathways?

Answer 1

Metabolic pathways are a series of enzyme-catalyzed reactions that convert a starting molecule into an end product through a series of metabolic intermediates. Many pathways are shared between organisms and cell types but some differ between cells.

Question 2

What are the two major purposes of metabolism?

Answer 2

.
1. To obtain usable chemical energy from the environment, either by capturing solar energy (photosynthesis) or consuming and breaking down nutrients.
2. To make the specific molecules that cells need to live and grow.

Question 3

What are the two main types of metabolic pathways?

Answer 3

○ Anabolic pathways: use energy to build larger molecules from smaller precursors and are generally reductive (electrons are gained to form new bonds).
○ Catabolic pathways: release energy (some of which is stored) by breaking down larger molecules and are generally oxidative (electrons are lost as bonds are broken).

Question 4

What are amphibolic pathways?

Answer 4

Amphibolic pathways can function in both anabolic and catabolic processes depending on the conditions.

Question 5

What are the most significant fuel sources for humans?

Answer 5

Polysaccharides (complex carbohydrates) that are broken down into monosaccharides (simple sugars) and triacylglycerol (fat), which is broken down into fatty acids.

Question 6

How are carbohydrates and fatty acids stored in the body?

Answer 6

○ Carbohydrates are stored as glycogen, a polymer of glucose, in the liver and skeletal muscle.
○ Fatty acids are stored as fat (triacylglycerols) in adipocytes.

Question 7

How is the oxidation state of carbon affected during catabolism?

Answer 7

Carbons in metabolites tend to become more oxidized. For example, a hydroxyl group might be converted to a carbonyl, or a carboxylate to carbon dioxide.

Oxidation is the loss of electrons during a reaction by a molecule

Question 8

Are fats more or less reduced than carbohydrates?

Answer 8

Fats (and fatty acids) are more reduced than carbohydrates.

Question 9

What is the typical end product of carbon catabolism?

Answer 9

Carbon dioxide

Question 10

What is the standard free energy change of a reaction?

Answer 10

Standard free energy change (ΔG°′) is a thermodynamic term that describes the free energy change of a reaction under standard conditions:
* ○ ΔG°′ = ΔG°′_{f, products} - ΔG°′_{f, reactants}
○ ΔG°′ = ΔH°′ – TΔS°′
○ ΔG°′ = -RTln(K′_eq)

(′) indicates the reaction is taking place under biochemical conditions

Question 11

What are biochemical standard conditions?

Answer 11

○ pH = 7
○ [S] & [P] = 1M
○ Temperature = 25°C/298K
○ Pressure = 1 atm
○ [H₂O] = 55M

Question 12

How does the actual free energy change of a reaction relate to the standard free energy change?

Answer 12

The actual free energy change (ΔG_reaction) depends on the concentrations of reactants and products present in the system:
○ ΔG_reaction = ΔG°′ + RTln([products]/[reactants])

Question 13

What does the sign of ΔG′ tell us about the spontaneity of a reaction?

Answer 13

○ ΔG′ > 0: The reaction will not occur spontaneously in the forward direction.
○ ΔG′ < 0: The reaction will occur spontaneously in the forward direction.
○ ΔG′ &laquo_space;0: The reaction is considered irreversible (i.e., it will only proceed in the forward direction).
○ ΔG′ ~ 0: The reaction is considered reversible (i.e., it can proceed in both the forward and reverse directions).

Question 14

How do the free energy changes of individual reactions in a pathway relate to the overall free energy change?

Answer 14

The free energy changes of individual reactions in a pathway are additive. For a pathway to proceed, the overall ΔG′ for the entire pathway must be negative (ΔG′ < 0). This is true for both catabolic and anabolic pathways.

Question 15

What does it mean for a metabolic pathway to exist in a steady-state?

Answer 15

When a metabolic pathway is operating in a steady state, the concentrations of metabolic intermediates remain relatively constant, even though there is a constant flux of metabolites through the pathway.

Question 16

Which steps in a metabolic pathway are typically regulated?

Answer 16

Irreversible steps (those with a large negative ΔG′) are usually regulated, while reversible steps are not. The rate-limiting step in a pathway is the irreversible, regulated reaction that determines the overall rate of the pathway.

Question 17

What are some common mechanisms of enzyme inhibition in metabolic pathways?

Answer 17

○ Product inhibition: An enzyme is inhibited by the product of its reaction.
○ Feedback inhibition: An enzyme is inhibited by a metabolite further down the pathway.

Question 18

What is feed-forward activation?

Answer 18

Feed-forward activation occurs when an enzyme is activated by a metabolite upstream in the pathway. This helps ensure that the pathway functions in concert and that intermediates do not accumulate.

Question 19

What is reciprocal regulation?

Answer 19

Reciprocal regulation occurs when opposing pathways (which catalyze the reverse reactions of one another) are regulated to ensure that both do not operate simultaneously.

Question 20

What are high-energy intermediates?

Answer 20

High-energy intermediates are compounds that contain “usable” chemical energy. This energy can be recovered for use in other reactions. These molecules have a simple reaction (hydrolysis) that is associated with a large, negative standard free-energy change (ΔG°′ < -25kJ/mol).

Question 21

What are the three major types of high-energy intermediates?

Answer 21

○ Electron carriers (NADH, NADPH, FADH₂, FMNH₂)
○ Nucleoside triphosphates (NTPs: e.g. ATP, UTP, GTP)
○Thioesters

Question 22

Describe the general roles of the electron carriers NAD⁺, NADP⁺, and FAD in metabolic reactions.

Answer 22

○ NAD⁺ and FAD are typically reduced during catabolic reactions (they act as oxidizing agents).
○ NADPH is typically oxidized during anabolic reactions (it acts as a reducing agent).

Question 23

How are the cofactors NAD⁺, NADP⁺, and FAD reduced?

Answer 23

These cofactors are reduced by the addition of two electrons and two protons:
○ NAD⁺ + 2H⁺ + 2e^- → NADH + H⁺
○ NADP⁺ + 2H⁺ + 2e^- → NADPH + H⁺
○ FAD + 2H⁺ + 2e^- → FADH₂

Question 24

What is the difference between a cosubstrate and a prosthetic group?

Answer 24

○ Cosubstrate: A molecule that binds transiently to an enzyme and is altered during the reaction. NAD⁺ and NADP⁺ are typically cosubstrates.
○ Prosthetic group: A molecule that is tightly (often covalently) bound to an enzyme. FAD is typically a prosthetic group.

Question 25

Why is ATP considered a high-energy molecule?

Answer 25

ATP contains two phosphoanhydride bonds, which have a large negative free energy of hydrolysis. This energy can be used to drive unfavorable reactions.

Question 26

What makes phosphoanhydride bonds high-energy?

Answer 26

The products of phosphoanhydride bond hydrolysis (ADP and inorganic phosphate) have greater resonance stabilization, decreased electrostatic repulsion, and are better solvated than ATP

Question 27

What is the approximate free energy change associated with the hydrolysis of a phosphoanhydride bond in ATP?

Answer 27

ΔG′° ≈ -32 kJ/mol

Question 28

What are the two main ways that ATP is generated?

Answer 28

○
Substrate-level phosphorylation: ATP is generated directly by the transfer of a phosphate group from a high-energy substrate to ADP.
○
Oxidative phosphorylation: ATP is generated by the reoxidation of NADH and FADH₂, which were reduced during catabolic reactions.

Question 29

How is ATP used in the cell?

Answer 29

○ Drive unfavorable reactions (coupling)
○ Power movement (muscle contraction, flagellar motion)
○ Fuel primary active transport (ion pumping)

Question 30

How can an unfavorable reaction (ΔG > 0) be driven forward?

Answer 30

An unfavorable reaction can be coupled to a favorable reaction (ΔG < 0) to give an overall negative free energy change, allowing the combined reactions to proceed spontaneously.

Question 31

What is phosphate transfer potential?

Answer 31

Phosphate transfer potential refers to the free energy of hydrolysis for a phosphate-containing compound. For example, ATP has a higher phosphate transfer potential than glucose-6-phosphate.

Question 32

What is the short-term source of ATP for muscle contraction?

Answer 32

Phosphocreatine can be used to rapidly generate ATP from ADP by substrate-level phosphorylation. The hydrolysis of phosphocreatine has a large negative ΔG′° (-43 kJ/mol), which allows it to drive the synthesis of ATP.