exam 3 practice Flashcards

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1
Q

glycolysis-acely CoA how it’s flowing
glugensis- expensive simile reversible reaction
carbon flow # of carbons pathways steps to get prepared to spilling
enzyme class hint in dehydrogenase
allosteric molecules

A
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2
Q

What is catabolism/anabolism?

A

They both manage energy and molecular requirements for living organisms
Catabolism: involves the breakdown of complex molecules into simple ones, releases energy in the form of ATP
Anabolism: the opposite of catabolism, building up complex molecules from numerous simple ones, consumes energy usually in the form of ATP, uses raw materials produced during catabolism to synthesize macromolecules, requiring an input of energy

food molecules through catabolic pathways lose heat and covert themselves into the many building blocks for biosynthesis. Catabolic pathways turn use full forms of energy in which anabolic pathways convert this into the many molecules that form the cell

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3
Q

Why do we breakdown food eg. glucose in small steps vs a quick reaction? what are the reductant and oxidant in a typical redox reaction?

A

Q1: free energy is released from sugar and stored in carrier molecules in the cell. small steps allow for a gradual release of energy making it easier for cells to capture and use the energy efficiently. quick reactions could waste energy as heat

Q2: reductant is the molecule that loses electrons and oxidant is the molecule that gains electrons

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4
Q

What is substrate-level phosphorylation?
What are the input and output materials of glycolysis, including the number of ATP and NADH molecules as well as the final product?
Describe the carbon flow through glycolysis.

A

Q1: substrate level is the process in glycolysis and citric acid cycle where directly produced by transferring a phosphate group from a substrate molecule to ADP, forming ATP.
Q2: Input: One glucose molecule (6 carbons), 2 ATP molecules, 2 NAD+ molecules.
Output: 4 ATP molecules (net gain of 2 ATP), 2 NADH molecules, 2 pyruvate molecules, and 2 water molecules.

Q3: Glycolysis starts with a 6-carbon glucose molecule and breaks it down into two 3-carbon pyruvate molecules through a series of enzyme-catalyzed reactions. These reactions involve several intermediate molecules and result in the release of energy in the form of ATP and the reduction of NAD+ to form NADH.
The rung must be opened, and then the glucose will be cleaved into 2 3-carbon molecules known as glyceraldehyde 3 phopshtare. These are straight chained.

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5
Q

What is the key regulatory step/enzyme of glycolysis? How is this enzyme regulated?

A

The key step is the conversion of fructose 6 phosphate to fructose 1,6 biphosphate by the enzyme phosphofructokinase PFK1.
PFK is regulated by levels of ATP and citrate.
HIGH ATP levels inhibit PFK, LOW ATP levels and high levels of AMP and fructose 2,6 bisphosphate activate it, promoting glycolytic activity
(Negative allosteric regulators) citrate, ATP, and proton (low pH, acidic); (positive allosteric regulators) AMP, fructose 2,6 biphosphate

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6
Q

Q: What high-energy bonds are formed in certain glycolysis stages? Provide examples.
Stage 1: energy investment phase
Stage 2: energy generation phase

A

Glycaldehyde 3-phosphate and glycaldehyde 3-phosphate dehyrogenase would form a high energy thio ester bond, the products 1,3 biphosphate glycerate would have a high energy phosphate group

Stage 1: energy investment phase
2 ATP molecules are used to form high-energy bonds during the early stages
Stage 2: energy generation phase
Conversion of 1,3bisphosphoglycerate to 3-phosphoglycerate creates a high-energy phosphate bond AND conversion of phosphoenolpyruvate to pyruvate also forms a high-energy phosphate bond.

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7
Q

What is the fate of pyruvate under anaerobic conditions?

A

Under anaerobic conditions, pyruvate can be converted into lactic acid (lactate) through fermentation in some organisms OR into ethanol and carbon dioxide through alcoholic fermentation. These processes regenerate NAD+ for glycolysis to continue when oxygen is not avail.

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8
Q

What is pyruvate converted to before entering the TCA cycle? What enzyme catalyzes this reaction?

A

pyruvate is transported to the mitochondrial matirx and is oxidized and converted to acetyl-CoA before entering the TCA (tricarboxylic acid) cycle.

This conversion is catalyzed by the enzyme pyruvate dehydrogenase.

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9
Q

Q1: What are the enzyme classes of the enzymes that generate NADH, FADH2, and GTP within the TCA cycle?

Q2: Describe the carbon flow through the TCA cycle.

A

Q1: Enzymes that generate NADH belong to the dehydrogenase class.
Enzymes that generate FADH2 belong to the succinate dehydrogenase class.
Enzymes that generate GTP belong to the substrate-level phosphorylation class.

Q2: TCA cycle begins with acetyl CoA, which is derived from the breakdown of pyruvate. The acetyl group then is combined with oxaloacetate to form citrate. Continuing a series of enzyme-catalyzed reactions, carbon atoms are released as carbon dioxide and intermediated are regenerated. It generates NADH, FADH2, and GTP/ATP and helps produce ATP in later stages of cellular respiration. The cycle continuously turns, carbons in the acetyl groups are fully oxidized and released as CO2

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10
Q

What products are produced by one turn of the TCA cycle?

A

3 NADH
1 FADH2
1 GTP (which can be converted into ATP)
2 carbon dioxide (CO2)
These products play important roles in energy production and carbon metabolism within the cell.

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11
Q

If a certain metabolic reaction is not spontaneous under standard conditions at equilibrium, how could it occur in the cell?

A

In the cell, non-spontaneous reactions can occur if they are coupled to a spontaneous reaction with a more negative Gibbs free energy (ΔG). For example, in the DHAP (dihydroxyacetone phosphate) to Glyceraldehyde 3-phosphate conversion step, the non-spontaneous reaction is coupled to the highly exergonic (spontaneous) phosphorylation of DHAP. This coupling of reactions ensures that the overall process is thermodynamically favorable, allowing non-spontaneous reactions to proceed inside the cell.

ATP

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12
Q

Q: What are the different ways that metabolism is regulated (i.e., regulation of enzymes within metabolic pathways)?

A

Allosteric Regulation: Enzymes have binding sites for activators or inhibitors that can change enzyme activity.
Feedback Inhibition: End product of a pathway inhibits an earlier enzyme to prevent overproduction.
Covalent Modification: Enzymes can be chemically modified (phosphorylation, etc.) to alter their activity.
Gene Expression Regulation: Control of enzyme production through gene transcription.
Substrate Availability: The concentration of reactants affects reaction rates.
Compartmentalization: Enzymes and substrates are confined to specific cellular compartments.
Hormonal Regulation: Hormones like insulin and glucagon influence metabolism.
pH and Temperature: Enzyme activity is influenced by pH and temperature.
Enzyme Degradation: Some enzymes have a limited lifespan and are degraded.
Competitive Inhibition: Molecules similar to substrates compete for enzyme active sites.
Positive Feedback: In some cases, a product activates an enzyme further down the pathway.

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13
Q

Q: What is the pathway that can make glucose from non-carbohydrate precursors?
Q: What are the key concepts of gluconeogenesis we discussed in class?

A

Q1 gluconeogenesis
Q2 Reverse of Glycolysis.
Utilizes non-carbohydrate substrates like pyruvate, lactate, amino acids, and glycerol.
Involves key enzymes: pyruvate carboxylase, PEPCK, glucose-6-phosphatase.
Energetically costly, requiring ATP and GTP.
Regulation by hormones (e.g., glucagon).
Occurs primarily in the liver and to a lesser extent in the kidneys.
Crucial for maintaining blood glucose levels during fasting or between meals.

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14
Q

Where do fats enter in the stages of metabolism?

A

Fats enter metabolism primarily through the process of lipolysis, where triglycerides also called adipose (fat molecules) are broken down into glycerol and fatty acids. Glycerol can enter glycolysis, and fatty acids can enter beta-oxidation to produce acetyl-CoA, which then enters the citric acid cycle (TCA cycle) to generate energy.

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15
Q

Do fats generate much energy why?
2: How do we store energy (in the form of sugar)?

A

A1: Yes, fats generate a significant amount of energy. Fats are highly efficient energy stores because they contain more carbon-hydrogen (C-H) bonds than carbohydrates or proteins. When these C-H bonds are oxidized during metabolism, they release a substantial amount of energy, making fats an excellent source of long-term energy storage. A gram of fat releases twice as much energy as a gram of glycogen

We store energy in a branched polysaccharide g, a polysaccharide made up of glucose molecules. Glycogen is stored primarily in the liver and muscles and can be rapidly broken down to release glucose when energy is needed.

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16
Q

How would the presence of glucose 6-phosphate and/or ATP affect the activity of the enzyme (glycogen phosphorylase) used to break it down?

A

The presence of glucose 6-phosphate and ATP inhibits the activity of glycogen phosphorylase.
Glucose 6-phosphate signals that glucose levels are sufficient, so there is no need to break down more glycogen.
ATP is an indicator of sufficient cellular energy, and it also inhibits glycogen phosphorylase to conserve energy resources.
When energy is needed (low glucose and low ATP), the enzyme becomes active to release glucose from glycogen for energy production.

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17
Q

efficiency means of

A

increase of channels
less channels more efficient
sub units

18
Q

Review the structure of the mitochondria: 2 membranes and 2 compartments. How is the transport of metabolites accomplished through each membrane?

A

Inner: impermeable, any movement between compartments must be mediated by transporter protein, protein concentration is higher on the outside of the inner membrane (towards inter-membrane space), negative charge on inside (towards matrix)

Outer- permeable to most small molecules and ions, contains porin (a protein which is essentially a large pore) “leaky” 60-0% protein

Compartments: matrix (CAC reactions and oxidations of pyruvate and fatty acids) and Inner membrane space( where proton gradient is)

Cristae (inward folds of inner membrane that increase its surface area)

Mitochondria will be near areas of high ATP utilization

19
Q

What mitochondria protein machinery convert?
Where the is the ETC located?
Where is ATP synthase located?

A

Electron transfer potential to phosphoryl transfer potential
Located in the inner membrane
also in the inner membrane

20
Q

Q1: Describe how a reactant is altered when it is oxidized in oxidative phosphorylation.
Q2: Describe how a reactant is altered when it is reduced in oxidative phosphorylation.
Q3: Describe how the coenzyme NADH is chemically altered in a redox reaction.
Q4: How about O2?

A

A1: when a redundant is oxidized, it loses electrons in this case coenzymes like NADH lose a H+. This process is an electron donation, resulting in a more positive charge

A2: When a reactant is reduced, it gains an electron and a H+. This is an electron acceptance, resulting in a more negative charge

A3: NADH is oxidized to NAD+ by donating two electrons and a proton (H+). The chemical alteration involves the removal of the electrons and a hydrogen ion.

A4: oxygen (O2) is the terminal electron acceptor. It is reduced to form water (H2O) by accepting electrons and protons. This reduction of oxygen is the final step in the electron transport chain and is essential for the generation of ATP.

21
Q

What does the value E′0 represent for a substance? What does a negative value for E′0 indicate? Positive?

A

E′0 represents the standard reduction potential of a substance, which indicates its tendency to gain electrons and be reduced.
A negative E′0 indicates a substance’s high electron-accepting ability, meaning it readily undergoes reduction move RIGHT TO LEFT
A positive E′0 indicates a substance’s lower electron-accepting ability, suggesting it is less likely to be reduced. MOVES LEFT TO RIGHT

22
Q

What is the equation that converts ∆E′0 to ∆G°’ for a redox reaction? How do you interpret the results from this calculation?

A

Equation: ∆G°’ = -nF∆E′0
Interpretation:
Negative ∆G°’ is favorable and indicates a spontaneous reaction.
Positive ∆G°’ is unfavorable and indicates a non-spontaneous reaction.
∆G°’ informs us about the energy available for cellular work and the feasibility of coupling reactions.

23
Q

What is the path of electrons through the electron transport chain (ETC) from NADH to oxygen, and what are the key components and their roles?

A

Complex I (NADH Dehydrogenase): NADH donates electrons; electrons pass through iron-sulfur clusters and FMN to ubiquinone (Q).

Ubiquinone (Coenzyme Q): Transfers electrons between complexes; accepts electrons from Complex I or Complex II and transfers them to Complex III.

Complex III (Cytochrome b-c1 Complex): Transfers electrons from ubiquinol (QH2) to cytochrome c.

Cytochrome c: Carries electrons from Complex III to Complex IV; contains a heme structure.

Complex IV (Cytochrome c Oxidase): Reduces oxygen (O2) to form water, utilizing electrons from cytochrome c.

These components have varying redox potentials, determining the direction of electron flow along the ETC.

24
Q

Where is the proton gradient established in the mitochondria, and what functions does this gradient serve?

A

The proton gradient is established in the inner mitochondrial membrane and serves to produce ATP (energy currency), regulate metabolism, generate heat, and maintain proper mitochondrial function

25
Q

How does the multi-subunit ATP synthase serve as both a transport protein and an enzyme in the conversion of energy to generate ATP?

A

Transport Protein (Proton Pump):

The F0 subunit of ATP synthase acts as a proton pump, moving protons (H+ ions) across the inner mitochondrial membrane.
This creates a proton gradient with more protons in the intermembrane space and fewer in the matrix.
Enzyme (ATP Synthase):

The F1 subunit, located in the mitochondrial matrix, functions as an enzyme.
The proton gradient induces conformational changes in F1, driving the rotation of catalytic sites.
As these sites rotate, they catalyze the synthesis of ATP from ADP and Pi.
The energy for ATP synthesis comes from the proton motive force, converting potential energy into chemical energy.
Conversion of Energy:

ATP synthase converts the potential energy stored in the proton gradient into chemical energy stored in ATP.
In essence, ATP synthase acts as a molecular machine that both transports protons and uses their flow and conformational changes to produce ATP, the cell’s primary energy currency.

26
Q

How would the efficiency of ATP synthase be affected by the number of channels within the rotor domain?

A

Increased Channels: More channels in the rotor domain can increase proton flux, potentially making ATP synthesis more efficient by producing ATP more quickly.
Decreased Channels: Fewer channels may slow proton flow, reducing ATP production efficiency.
Optimal Channel Number: The number of channels is finely tuned to match the cell’s energy needs, balancing ATP production with minimal proton leakage and energy waste.

27
Q

Q1: ATP Yield from NADH and FADH2 in oxidative phosphorylation?
Q2: why is there less ATp produced when FADH2 donates its electrons in the ETC
Q3: what is the net yield of ATP for the complete oxidation of glucose to CO2 and H2O

A

Q1: NADH generates about 2.5 to 3 ATP. FADH2 generates about 1.5 to 2 ATP
Q2: ADH2 generates less ATP because it enters the electron transport chain at a later point, resulting in a smaller proton gradient and, therefore, less ATP production.
Q3: The net ATP yield for the complete oxidation of glucose to CO2 and H2O is approximately 30-32 ATP, with some variation due to factors like shuttle systems.

28
Q

What are the 2 main routes for drug absorption in drug metabolism?

A

Oral Absorption: Through the gastrointestinal tract, e.g., via tablets or liquids.
Parenteral Absorption: Direct administration into the bloodstream, e.g., IV, IM, SC injections.

29
Q

What are the factors influencing diffusion in passive transport according to Fick’s first law?

A

Concentration Gradient: Greater concentration difference accelerates diffusion.
Surface Area: A larger area facilitates more diffusion.
Distance: A shorter distance reduces diffusion time.
Diffusion Coefficient: A higher coefficient enhances diffusion efficiency.
Temperature: Increased temperature speeds up diffusion.

30
Q

How does ionization of a drug affect membrane permeability and absorption?

A

Ionized form is less permeable (hydrophilic).
Non-ionized form is more permeable (lipophilic).
pH influences ionization.
Matching drug pH to absorption site improves absorption.

31
Q

What are the two major superfamilies of human transporters and examples from each?

A

ABC Transporters:

Characteristics: Use ATP energy for transport. Has 2 transmembrane domains and 2 ATP binding sites
Example: P-glycoprotein (P-gp), It pumps various drugs and toxins out of cells, contributing to multidrug resistance in cancer therapy.

SLC Transporters:

Characteristics: Use facilitated diffusion or secondary transport.
Example: PEPT1 (SLC15A1), responsible for transporting di- and tripeptides. It is found in the small intestine and plays a crucial role in the absorption of dietary peptides.

32
Q

How does albumin binding affect the availability of a drug at the target site of action in drug distribution? What concern arises if albumin levels are lower than normal when administering a drug with high albumin binding affinity?

A

Effect of Albumin Binding: Albumin binding can decrease the free (unbound) fraction of a drug in the bloodstream. This may reduce the drug’s availability to reach and interact with its target site of action.

Concern with Low Albumin Levels: If a patient has lower-than-normal albumin levels and is administered a drug with high albumin binding affinity, there is a risk of increased free drug concentrations. This can lead to potential drug toxicity or side effects due to a higher effective dose of the drug. Adjusting drug dosage or considering alternative medications may be necessary.

33
Q

What’s the main difference in structural change between phase I and phase II drug metabolism?

A

Phase I (Structural Change): Introduces or unmasks functional groups. often through oxidation, reduction, or hydrolysis. ake the drug molecule more polar and water-soluble but may or may not lead to full elimination from the body.

Phase II (Structural Change): Involves conjugation with larger molecules such as glucuronic acid, sulfate, or amino acids. Conjugation increases the drug’s water solubility

34
Q

What happens to drug availability when there’s inhibition or activation of the cytochrome P450 responsible for drug metabolism (e.g., drug-drug or food-drug interactions)

A

Inhibition: Reduces drug metabolism, leading to higher drug levels and potential toxicity.
Activation: Accelerates drug metabolism, potentially lowering drug levels and reducing effectiveness.

35
Q

What are MEC and MTC in relation to pharmacokinetic graphs?

A

MEC (Minimum Effective Concentration): The lowest drug concentration at which a therapeutic effect occurs.
MTC (Minimum Toxic Concentration): The lowest drug concentration at which toxic effects start to appear.

36
Q

What are the enzyme reactions involved in ethanol metabolism, and what are the products of these reactions?

A

Alcohol Dehydrogenase: Converts ethanol to acetaldehyde.
Aldehyde Dehydrogenase: Converts acetaldehyde to acetate (acetic acid).
Microsomal Ethanol Oxidizing System (MEOS): An alternative pathway for ethanol metabolism.
Products: Ethanol -> Acetaldehyde -> Acetate.

37
Q

What impact does alcohol have on metabolic pathways in the cell, particularly in relation to NADH?

A

Alcohol consumption increases NADH levels and disrupts the balance of NADH/NAD+ in cells. This can affect various metabolic pathways, leading to decreased fatty acid oxidation, altered glucose metabolism, and potential liver damage.

38
Q

What harmful effect does acetaldehyde have?

A

Acetaldehyde is a toxic compound that can cause various harmful effects, including liver damage, DNA damage, and the development of alcohol-related health issues, such as alcoholic liver disease and certain types of cancer.

39
Q

What does CYP2E1 do, and what are the consequences of its activity?

A

CYP2E1 (Cytochrome P450 2E1): It is an enzyme that metabolizes various substances, including ethanol and some toxins.
Consequences: CYP2E1 activity can lead to the generation of toxic metabolites and contribute to oxidative stress and liver damage, particularly in the context of alcohol metabolism.

40
Q

How can ethanol metabolism directly affect the epigenome through histone modification?

A

Ethanol metabolism alters the NAD+/NADH ratio.
Changes in NAD+/NADH affect the activity of histone deacetylases (HDACs).
Altered HDAC activity can lead to histone hyperacetylation, impacting gene expression and potentially contributing to epigenetic changes.
These epigenetic modifications may influence various cellular processes and have implications for conditions like alcohol use disorders.