Biochem 2 Flashcards

Question 1

Q

Electron Transport Chain
- Explain why the oxidation of FADH₂produces fewer ATP than the oxidation of NADH (2 as opposed to 3)
- What does ATP synthase require to function?
- How does the proton gradient affect the rate of ATP synthase?

Answer

A

When NADH is oxidized, the electrons flow through:
- Complexes 1, 3, and 4
  - Complex 1 pumps 4 electrons
When FADH₂ is oxidized, the electrons flow through:
- Complexes 2, 3, and 4
  - Complex 2 pumps 0 electrons
Because Complex I pumps 4 electrons and Complex II pumps 0 electrons…
- oxidation of FADH₂ results in fewer protons being pumped.
ATP synthase requires the proton gradient to function
- so fewer protons pumped will result in fewer ATPs generated.

Question 2

Q

Organism-Level Regulation of Metabolism
- Metabolic States
  - Describe Well-Fed State
    - a.k.a., “Postprandial”, “Absorptive”

Answer

A

= First few hours after eating a meal
High insulin levels; low glucagon levels
High relative rate of anabolism (vs. catabolism)
- High rate of glycogen synthesis
- High rate of fatty acid synthesis

Question 3

Q

Pentose Phosphate Pathway (PPP)
- How many NADPH are produced per G6P molecule by the PPP?
- How many glutathione molecules are produced per G6P by the PPP?

Answer

A

NADPH:
For each G6P molecule:

two NADPH molecules are generated
- Both come from G6P converting to Ribulose 5-phosphate

Glutathione:

The PPP does not DIRECTLY generate glutathione molecules.
- However, the NADPH generated in the PPP can be used to:
  - reduce the oxidized form of glutathione
    - …to protect the cell from reactive oxygen species.
To regenerate glutathione, the reaction is:
- 1 glutathione disulfide + NADPH → 2 glutathione + NADP+
  - This means that for each G6P, four glutathiones are generated
    - because two NADPHs are generated

Question 4

Q

Citric Acid Cycle
- All-in-all, how much of the following is produced?
  - ATP
  - NADH
  - FADH₂
  - CO₂
- How much total NADH and FADH₂have been produced at this point (including Glycolysis)?

Answer

A

CAC produces:
- 2 ATP
- 6 NADH
- 2 FADH₂
- 4 CO₂
Total (CAC + Glycolysis):
- 10 NADH
- 2 FADH

Question 5

Q

Bioenergetics & Thermodynamics
- Noteworthy Differences between “Lab Thermodynamics” and Bioenergetics in Living Systems
  - What must “Living Systems” maintain?

Answer

A

Living systems must maintain a NON-equilibrium state!
Many aspects of a living system require a large, negative ΔS due to all macromolecules and systems being highly ordered compared to their precursors.
ΔG for many anabolic and metabolic biochemistry reactions is positive

Question 6

Q

Bioenergetics & Thermodynamics
- Noteworthy Differences between “Lab Thermodynamics” and Bioenergetics in Living Systems
  - Three students are reviewing a chart in their biochemistry text showing that many of the individual steps of glycolysis have a positive ΔG°’ value.
  - Discuss the accuracy and merits of their competing explanations for why glycolysis still occurs readily in living systems:
  - Student A) Enzymes are the solution! Enzymes drastically lower the free energy change to be more negative.
  - Student B) Food energy is the solution! Many biochemical reactions are unfavorable and that is why we must eat—to provide external energy to drive these reactions and maintain disequilibrium.
  - Student C) Reaction coupling is the solution! While some reactions are unfavorable, they are coupled to reactions that are favorable.

Answer

A

Several steps in glycolysis have positive ΔG’s, but the pathway still occurs spontaneously in cells.
The first student hypothesizes that this is due to enzymes lowering the free energy of the equation.
- However, the ΔG listed for the steps of glycolysis take the enzymes into account, and so the enzymes themselves cannot account for the spontaneity of the overall pathway.
Student B thinks that food energy is the solution, and that eating will give the energy needed to drive glycolysis.
- However, glycolysis is the process through which the body breaks down glucose, which is how the body gains energy from starchy food, so eating more wouldn’t drive the reaction forward.
- It would instead put more glucose into the system, requiring even more glycolysis action.
Student C is correct, reaction coupling will drive the entire pathway forward.
- Some steps in glycolysis have positive ΔG’s, but other steps have very negative ΔG’s.
- Those steps require the products of previous steps.
- Because the reactions are linked by the product of one reaction providing the substrates of the following reactions, the very negative ΔG’s will pull the pathway forward, even though the positive ΔG’s are earlier in the pathway than the very negative ΔG’s

Question 7

Q

Carbohydrate Metabolism
- Give a general definition for “Carbohydrate Metabolism”
- Also, define “Respiration” in this context

Answer

A

General Definition:
- The sum (Σ)of all chemical reactions in the body
Respiration:
- “the breakdown of macromolecules into smaller species to harvest energy in the form of ATP”

Question 8

Q

Carbohydrate Metabolism
- Clarify the difference between aerobic and anaerobic respiration
- Which one do humans use? When would we use the other?
  - What happens as a result of using the other?
- What does “Anaerobic respiration” typically refer to?

Answer

A

Respiration is a process in which an inorganic compound serves as the ultimate electron acceptor
- …in order to generate ATP
Aerobic respiration:
- uses oxygen as the final electron acceptor
Anaerobic respiration:
- uses a molecule other than oxygen
For question purposes, aerobic respiration involves all the reactions involved in:
- the citric acid cycle (CAC)
- electron transport chain (ETC)
Humans use aerobic respiration to generate the vast majority of our ATP
However, we use anaerobic respiration in our muscles during exercise
- which results in a buildup of lactic acid
Anaerobic respiration will typically refer to fermentation:
- using glycolysis in the absence of oxygen
- or the lactic acid cycle in muscles
Many bacteria and yeast use anaerobic respiration, including during fermentation

Question 9

Q

Lipid Metabolism
- Ketone Bodies
  - Describe

Answer

A

Formed by the liver
- during prolonged fasting periods
- as byproducts of increased fatty acid metabolism
Two of the three can be used for energy during fasting periods by the heart and brain.
Ketone bodies CANNOT be used by the liver during fasting
- because it lacks β-ketoacyl-CoA transferase

Question 10

Q

Organism-Level Regulation of Metabolism
- Metabolic States
  - Name the 3 kinds of Metabolic States

Answer

A

Well-Fed State
- a.k.a., “Postprandial”, “Absorptive”
Fasting State
- a.k.a., “Postabsorptive”
Starvation

Question 11

Q

Feeder Pathways for GLY

FRUCTOSE Metabolism In the LIVER
- Fructose⇒___⇒___+____⇒___
  - Describe the 3 sequential rxns

What step of Glycolysis does this funnel into?

Answer

A

LIVER:

Fructokinase converts:
- Fructose⇒Fructose-1P
Fructose-1-P ALDOLASE converts:
- Fructose-1P ⇒Glyceraldehyde 3-Phosphate (GAP) + DHAP
Triose Phosphate Isomerase converts:
- DHAP⇒ GAP

⇒5^th step GLY

(Will get converted to 1,3 Bisphosphoglycerate by GAPDH)

Question 12

Q

Biochemical Shuttles
- Citrate-Acetyl-CoA Shuttle (Tricarboxylate Transport System, TTS)
  - What is the Problem & Solution?
  - During what periods is this shuttle needed?

Answer

A

PROBLEM:
- During periods of energy abundance, Acetyl-CoA groups in the mitochondria are redirected from the CAC to fatty acid synthesis
- However, fatty acid synthesis occurs in the cytosol and Acetyl-CoA cannot pass through the inner mitochondrial membrane
SOLUTION:
- Acetyl-CoA is combined with OAA to form citrate
  - (this is the normal 1^ststep of CAC)
- Citrate IS able to pass through the membrane
  - and is then converted back to OAA and Acetyl-CoA in the cytosol.

Question 13

Q

Principles of Bioenergetics
- ΔG=?
  - What does each part represent?
  - Here, how should you think of ΔG and ΔG°’?

Answer

A

ΔG = ΔG°’ + RTlnQ
- R =Universal Gas Law constant
- T=temperature
- Q=reaction quotient

Think of ΔG°’ as:
- the fixed, unchangeable value
  - ΔG°’ is fixed and predetermined for a given reaction at a given temperature
  - It ONLY represents the reaction under all of those strictly standardized criteria
Think of ΔG as:
- the variable one
  - ΔG can be measured anywhere, at any time during a reaction
  - Pause the reaction at any precise moment of your choosing, subtract the sum of the free energy of the reactants present at that moment from the sum of the free energy of the products present at that moment
    - The resulting value will be ΔG

Question 14

Q

Lipid Metabolism

Name the 3 types of KETONE BODIES
- which DO have energy value, which DONT?

Answer

A

Acetone
- NO energy value
Acetoacetate
- HAS energy value
3-Hydroxybutyrate
- HAS energy value

Question 15

Q

Organism-Level Regulation of Metabolism
- What does the Brain, Adipose Tissue, and Erythrocytes (RBC’s) use for fuel during well-fed states and during fasting states?

Answer

A

Brain
- Glucose during well-fed state
- Glucose if fasting
  - Ketones if prolonged fast or starvation
Adipose Tissue
- Glucose in well-fed state
- Fatty acids during fasting
Red Blood Cells
- Glucose in ALL states
  - ALWAYS via ANAEROBIC glycolysis!!!
  - aka FERMENTATION

Question 16

Q

Regulation of Carbohydrate Metabolism
- Hormonal Control
  - Pentose Phosphate Pathway
    - Identify all molecules that:
    - upregulate the process
    - downregulate the process
    - Specify the exact enzyme or step with which the regulatory molecule interacts.

Answer

A

The pentose phosphate pathway is primarily controlled by the levels of NADP+ .
The first enzyme, glucose 6-phosphate dehydrogenase (G6PDH), is inhibited by:
- NADP+
  - because NADP+ is needed as the electron acceptor for the reaction.

Question 17

Q

Lipid Metabolism
- β-Oxidation
  - Location=? (except for?)
  - What are the Problem & Solution?

Answer

A

Location
- Mitochondrial matrix
- Exception:
  - Extra-long-chain fatty acids first enter a peroxisome and are catabolized into smaller pieces
    - These pieces can then be oxidized in the mitochondria
PROBLEM:
- Activated fatty acids cannot cross the inner mitochondrial membrane to reach the matrix
SOLUTION:
- Carnitine Shuttle (Carnitine-acylcarnitine translocase)

Question 18

Q

Adenosine Triphosphate (ATP)
- Consumption of ATP
  - Name the 3 ways ATP is consumed (that we need to know for MCAT)

Answer

A

Hydrolysis
Phosphoryl Group Transfers
Phosphorylation using ATP

Question 19

Q

Bioenergetics & Thermodynamics
- Describe the “Fundamental Thermodynamic Relation” that correlates enthalpy, entropy and Gibbs free energy.
- Draw a four quadrant chart showing all possible combinations for the signs of ΔS and ΔH for a reaction.
  - For each scenario predict the sign of ΔG and whether or not the reaction will be spontaneous

Answer

A

The fundamental thermodynamic=
- ΔG=ΔH-TΔS
Spontaneous if…
- ΔG is less than 0
Non-spontaneous if…
- ΔG is greater than 0
At equilibrium if…
- ΔG is = 0
A reaction is favorable if…
- ΔH is negative and/or ΔS is positive.
  - When ΔH is negative and ΔS is positive, the reaction will be spontaneous
- When ΔH is positive and ΔS is negative, the reaction will not be spontaneous
In any other situation, the result will depend on the values of H and S

Question 20

Q

Lipid Metabolism
- β-Oxidation of fatty acids
  - In β-Oxidation, where on the FA are double bonds created?
  - What happens if you come across a double bond that isnt in that position?
    - What enzyme do you need to fix it?

Answer

A

Normal β-oxidation includes the creation of a double bond in the 2-3 position
- As successive rounds of oxidation occur, if a double bond ends up in this position, things may proceed as normal
If double bond is in another position (like 3-4), β-oxidation cannot occur
- Enoyl-CoA isomerase catalyzes the movement of double bonds to the 2-3 position
  - Oxidation can again proceed

Question 21

Q

Lipid Metabolism

What are some potentially confusing LOCATION ISSUES wrt lipid metabolism and FA synthesis?

Answer

A

LIPIDS

metabolized for energy in
- the mitochondria
synthesized
- in the cytosol
  - (mostly hepatocytes)
modified
- at the SER

FATTY ACID SYNTHESIS

occurs in the cytosol
- stops at the 16-carbon palmitic acid
  - technically, it ends by forming palmitoyl-CoA
Elongation and modification (e.g., desaturation)
- occur at the Smooth ER

Question 22

Q

Carbohydrate Metabolism
- What is the difference between an obligate aerobe and a facultative aerobe?
- Between an obligate and a facultative ANAEROBE?
- Which one are you?

Answer

A

“Obligate”
- implies that there is no other option, so obligate aerobes must use aerobic respiration and cannot survive without oxygen, while obligate anaerobes must use anaerobic respiration and cannot survive in the presence of oxygen.
“Facultative”
- implies that the organism will use WHICHEVER RESPIRATION IS AVAILABLE
- So if oxygen is present, the organism will use aerobic respiration, and if oxygen is absent, the organism will use anaerobic respiration.
Facultative anaerobes prefer anaerobic respiration but will use aerobic if needed.
Facultative aerobes prefer aerobic respiration but will use anaerobic if needed
∴ HUMANS ARE “FACULTATIVE AEROBES”

Question 23

Q

Bioenergetics & Thermodynamics
- Define “Bioenergetics”
- What is it analogous to?

Answer

A

Bioenergetics
- The thermodynamics of biological systems
is analogous to biochemistry being the “chemistry” of biological systems

Question 24

Q

Adenosine Triphosphate (ATP)
- Formation of ATP
  - Substrate-Level Phosphorylation
    - Define. What must be coupled to this process in order to proceed?
    - LOCATION this happens?
    - Give an EXAMPLE of this

Answer

A

Substrate-Level Phosphorylation
- Formation of ATP from ADP in which the source of the necessary phosphate is a phosphate bound to another molecule (i.e., the “substrate”)
- To proceed, this process MUST be coupled to an EXERgonic reaction
LOCATION:
- Primarily in the cytosol
  - as part of glycolysis
- Also in the matrix of the mitochondria
  - where GTP is formed during the CAC
EXAMPLE:
- The ATP formed during glycolysis is an example of substrate-level phosphorylation

Question 25

Q

Glycolysis
- Enzyme mnemonic=?

Answer

A

Hot
- Hexokinase
Pussy
- Phosphoglucose isomerase
Practically
- PFK-1
Always
- Aldolase
Takes
- Triose Phosphate Isomerase
Great
- G3P Dehydrogenase (G3PDH)
Patience
- Phosphoglycerate Kinase
Preparing
- Phosphoglycerate Mutase
Eventual
- Enolase
Penetration
- Pyruvate Kinase

Question 26

Q

Anabolism of Fats & Carbohydrates
- Describe Non-Template Synthesis
  - Why is the moniker “Non-Template” used to describe it?

Answer

A

Non-Template Synthesis:
- Biosynthesis of lipids and polysaccharides (carbohydrates)
- The moniker “non-template” is used because the synthesis of fats and carbohydrates does not follow a template
  - …as do protein and nucleic acid synthesis

Question 27

Q

Regulation of Carbohydrate Metabolism
- Hormonal Control
  - GLUCONEOGENESIS:
    - identify all molecules that:
      - upregulate the process
      - downregulate the given process.
      - Specify the exact enzyme or step with which the regulatory molecule interacts

Answer

A

Gluconeogenesis is needed when energy levels are high and glucose levels are low
- the opposite of when glycolysis is needed.
- As such, the enzymes are regulated oppositely to those in glycolysis such that when one pathway is activated, the other is being actively inhibited, and vice versa.
Fructose 1,6-bisphosphatase
- inhibited by AMP
- stimulated by ATP
- exactly opposite of its glycolysis counterpart
  - phosphofructokinase.
Both:
- pyruvate carboxylase and
- phosphoenolpyruvate
  - are inhibited by ADP
These enzymes are the counterpart to pyruvate kinase in glycolysis

Question 28

Q

Principles of Bioenergetics
- Describe the difference between ΔG, ΔG°, and ΔG°’
- What should you remember about the last two?

Answer

A

It is important to remember that a reaction is almost never going to be in these conditions!!!

ΔG
- Free energy change at some present, non-standard set of conditions.
ΔG°
- Free energy change at standard conditions:
  - 25°C
  - 1 atm
  - [1M] of all species
ΔG°’
- Free energy change at standard physiological conditions, pH = 7
For the MCAT, think of ΔG° and ΔG°’ as essentially the same thing
They both represent a standard state “from-the-textbook-table” value for Gibbs free energy calculated at a point where we have the exact same concentrations of all species, both products and reactants (i.e., Q = 1).
Just remember that the prime (’) symbol means it is at physiological pH, too

Question 29

Q

Differences between “LAB Thermodynamics” and Bioenergetics in LIVING Systems

Describe the Dynamic Steady State (aka…?)
- Give a real-life example of it

Answer

A

The Dynamic Steady State

(a. k.a., Homeostasis)
* Describes the ability of living things to maintain a constant, steady internal environment that is NOT in equilibrium with its surroundings.

EXAMPLE: BODY TEMP

For example, your body temperature remains a fairly constant 98.6°F, and yet the room you are in right now is probably about 75°F.
- Further, the environment around you is in constant decay—moving organized, complex, high-energy states toward disorganized, simpler, low-energy states.

Question 30

Q

Standard Free Energy Change (ΔG°’) and the Equilibrium Constant (K_eq)
- Spontaneous Reactions or Processes
  - Differentiate b/t ENDERgonic & EXERgonic

Answer

A

Endergonic
- ΔG is positive = nonspontaneous
Exergonic
- ΔG is negative = spontaneous

Question 31

Q

Pentose Phosphate Pathway (PPP)

Describe the Oxidative Phase

__–>__–>__–>__?
Since the first 2 steps are UNfavorable, what EXERgonic reaction are they coupled to?
What do NADPH and R5P each do in this phase?

Answer

A

OXIDATIVE PHASE:

Glucose-6-P ⇒

6-Phosphogluconate ⇒

Rib**ulose**-5-P ⇒

Ribose-5-P

The first two steps outlined above are both coupled to:

the conversion of NADP+ to NADPH

NADPH is used to:

REDUCE glutathione disulfide (GSSH) to glutathione (2GSH)
Act as a COFACTOR for reductive biosynthesis

R5P

is funneled into NT synthesis

Question 32

Q

Citric Acid Cycle
- Diagram
  - Include:
    - species that enter and exit the cycle
      - including where they originated from and where they will go next
  - the starting substrate and final product of each step,
  - when and where CO2 is produced
  - changes to the carbon skeleton
  - any points in the cycle where NAD+ , NADH, FAD, FADH2, ADP, GDP, ATP or GTP are either required or produced.

Question 33

Q

Glycolysis

Aldolase catalyzes the breakdown of Fructose 1,6-bisphosphate (F1,6BP) into:

one molecule of glyceraldehyde-3-phosphate (G3P)
one molecule of dihydroxyacetone-phosphate (DHAP)

If the 2’ carbon of F1,6BP is radioactively labeled, aldolase is allowed to turnover a large number of molecules, and isomerase activity is blocked, how will the radio label be distributed?

a) equally between F1,6BP and DHAP molecules
b) only on F1,6BP molecules
c) only on DHAP molecules

Answer

A

All the radiolabeled molecules will be dihydroxyacetone phosphate (DHAP)
This is because when fructose 1,6-bisphosphate is cleaved, it is cleaved the same way every time
- Carbons 1, 2, and 3 become:
  - dihydroxyacetone phosphate (DHAP)
- Carbons 4, 5, and 6 become:
  - Glyceraldehyde 3- phosphate (G3P)
∴ if carbon 2 is labeled, the labeled molecule will always be DHAP
If the isomerase is active, some of the DHAP will be converted to GAP, so the label will be distributed between the two
But without the isomerase, all labeled molecules will be DHAP

Question 34

Q

Electron Transport Chain
- Using the NADH and FADH₂ equivalents given,demonstrate for the complete oxidation of one glucose molecule:
  - where each high energy molecule is created
  - how they add up to 36 ATP per glucose
- HINT: Two common errors are
  1. not considering the “net” ATP from glycolysis
  2. ignoring the ATP required for the transport of NADH into the mitochondria

Answer

A

The overall reaction for GLYCOLYSIS is
- glucose + 2 NAD⁺ + 2P_i+ 2 ADP⇒2 pyruvate + 2ATP + 2NADH + 2H⁺
The overall reaction for the CITRIC ACID CYCLE (including PDC) is:
- pyruvate + 4 NAD⁺ + FAD + GDP + P_i + 2 H₂0 ⇒3 CO₂ + 4NADH + 4H⁺ + GTP + FADH₂
Keep in mind that you’ll need to DOUBLE the citric acid cycle equation
- because glycolysis results in TWO (!) pyruvates
This means that from complete oxidation of one glucose, we get:
- (see attached)
NADH = 3 ATP
FADH₂ = 2 ATP
NADH from glycolysis = 2 ATP
- (because it costs 1 ATP to transport it in)
Total, we have (2 x 2) + (8 x 3) + (2 x 2) + 4 = 36 ATPs

Question 35

Q

Organism-Level Regulation of Metabolism
- Tissue-Specific Metabolism
  - Different tissues use different ____ ____ preferentially
  - What does the Liver prefer during well-fed & fasting states?

Answer

A

Different tissues use different fuel sources preferentially
in the Liver:
- Glucose in well-fed state
- Fatty acids during fasting
  - but NO ketones (lacks enzyme)

Question 36

Q

Biochemical shuttles
- What are the 4 shuttles we need to know for the MCAT?

Answer

A

Malate-Aspartate Shuttle
Glycerol-3-Phosphate Shuttle
Carnitite Shuttle
Citrate-Acetyl-CoA Shuttle
- aka Tricarboxylate Transport System, “TTS”

Question 37

Q

Lipid Metabolism
- β-Oxidation
  - Draw a mechanism for the beta-oxidation of a fatty acid
  - Indicate the point at which FADH² and NADH are produced

Question 38

Q

Lipid Metabolism
- β-Oxidation of fatty acids
  - What happens in β-Oxidation when you have a conjugated double bond?
    - What enzymes (2) are needed to continue β-Oxidation?

Answer

A

β-Oxidation cannot proceed through conjugated DB’s
Needs 2 enzymes:
1. 2-4 dienoyl-CoA reductase
  - converts 2 DB’s to 1 DB
2. Enoyl-CoA isomerase
  - to move the DB’s to the 2-3 position

Question 39

Q

Regulation of Carbohydrate Metabolism
- Hormonal Control
  - Catecholamines (3)
    - Describe the 3 types and what they do wrt metabolism

Answer

A

Catecholamines are derived from tyrosine and have an amine side group
3 Types:
- Dopamine, Epinephrine, and Norepinephrine
Dopamine
- is a CNS neurotransmitter
Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)
- are the two metabolic hormones
Catecholamines also have a “glucagon-like” effect (like Cortisol)
…but should be thought of as causing a more rapid “mobilization” of energy stores
- which are necessary for the “fight or flight” response
Fatty acids are mobilized for oxidation and glycogenolysis is increased

Question 40

Q

Regulation of Carbohydrate Metabolism
- Hormonal Control
  - GLYCOGENESIS
    - identify all molecules that:
    - upregulate the process
    - downregulate the process
    - Specify the exact enzyme or step with which the regulatory molecule interacts

Answer

A

Glycogenesis, the synethesis of glygogen, is regulated oppositely to glycogenolysis.
When glucagon and epinephrine are present in the bloodstream
- …the cAMP cascade is stimulated
Protein kinase A phosphorylates glycogen synthase
- this phosphorylation inhibits the enzyme (instead of activating, as it does with glycogen phosphorylase)
When the cAMP cascade is withdrawn, protein phosphorylase I will dephosphorylate glycogen synthase
- stimulating glycogen synthesis
- This way, the same stimulus will simultaneously shut down one pathway and turn on the other

Question 41

Q

Regulation of Carbohydrate Metabolism
- Allosteric Control
  - Describe an Allosteric Enzyme

Answer

A

ALLOSTERIC ENZYMES
- Enzymes that change conformation and/or affinity for their substrate upon binding of an allosteric regulator molecule

Question 42

Q

Obesity and Regulation of Body Mass

What 3 things go into “Body Mass Regulation?”
What 3 hormones are involved in obesity?
Threshold for weight GAIN is ____ than for weight LOSS
Healthy individuals burn ___ first, then ___, then ___

Answer

A

Body Mass Regulation is a combination of:

Hormones
Food intake
Activity level

Hormones:

Leptin
Ghrelin
Orexin

Threshold for weight gain is LOWER*
than for weight loss*

Healthy individuals burn:

Carbohydrates first
then fats
then proteins

Question 43

Q

Gluconeogenesis
- Redraw a simplified glycolysis chart and demonstrate the alternative pathways used to accomplish gluconeogenesis
- Identify any enzymes that are NOT part of glycolysis

Question 44

Q

For GLYCOLYSIS, identify :

All molecules that INHIBIT
- Specify the exact enzyme or step with which the regulatory molecule interacts

Hint: There are 3 regulated enzymes in glycolysis

Answer

A

GLYCOLYSIS

three (3) reactions are regulated.
- Keep in mind that glycolysis is needed when energy in the cell is low
  - so regulation will be such that enzymes are activated by a lack of energy and inhibited when energy is abundant

1) PFK-1

INHIBITED BY: ATP

AMP reverses the inhibition of ATP
Thus, the ratio of ATP to AMP is crucial to determining the activity of glycolysis*

2) Hexokinase

_INHIBITED BY: G6P (ITS PRODUCT)_

Because glucose and glycogen are both converted to G6P
- When this molecule is at high concentration, hexokinase is inhibited, because the cell has plenty of access to energy
  - Glucose will stay at higher concentrations in the blood or
  - Be converted to glycogen for storage

3) Pyruvate Kinase

INHIBITED BY: ATP, ALANINE

Alanine also inhibits pyruvate kinase
- because pyruvate is used as a building block for AAs

a high concentration of alanine signals that building blocks aren’t needed

Question 45

Q

Fermentation (Anaerobic Glycolysis)
- Why is fermentation important in bacteria?
- When is the only time fermentation is used by animals?
- What kind of cell also uses fermentation?

Answer

A

For most bacteria, this is the sole route of metabolizing glucose
Fermentation is used by animals only during:
- oxygen debt (aka periods of prolonged exercise)
Also used by:
- erythrocytes

Question 46

Q

Regulation of Carb Metabolism

Hormonal Control

Describe “Glucocorticoids”

What kind of effect do they have on metabolism?
- What 3 things do they stimulate?
Glucocorticoids also reduce _________
Most significant example of a glucocorticoid is ______

Answer

A

Glucocorticoids have a “GLUCAGON-LIKE”

effect on metabolism

Stimulating:
1. Gluconeogenesis
2. Glycogenolysis
3. Fatty acid oxidation
Glucocorticoids also reduce inflammation

Cortisol is the most significant example

Recall that cortisol is produced by the adrenal cortex
- in response to ACTH from the anterior pituitary
  *

Question 47

Q

Formation of ATP

Describe OXIDATIVE Phosphorylation
- In what LOCATION does this happen in?
- Give an EXAMPLE of this

Answer

A

Oxidative Phosphorylation

Formation of ATP out of ADP and Free Organic Phosphate (Pi) by harnessing the energy of the proton gradient across the inner mitochondrial membrane.

This proton gradient is created as a result of coupling:

the oxidation of high-energy molecules
- such as NADH and FADH₂
…to the pumping of protons
- out of the complexes in the ETC

LOCATION:

EXCLUSIVELY in the MITOCHONDRIAL MATRIX

EXAMPLE:

The ATP formed by ATP Synthase in the mitochondria

Question 48

Q

Protein Metabolism
- Transamination
  - Describe
  - Give an example
  - What role does transamination play in Protein Metabolism?

Answer

A

A key step in protein metabolism for energy is transamination of amino acids–
- or the exchange of an amine group on one molecule for a carbonyl group on another.
For example, transamination of Glu forms alpha-ketoglutarate
- …which is an intermediate in the Citric Acid Cycle
Transamination is what helps AA’s that are unable to be broken down into pyruvate or acetyl-CoA GET INTO THE CITRIC ACID CYCLE

Question 49

Q

Protein Metabolism
- Differentiate between ketogenic and glucogenic amino acids.
  - Which amino acids are exclusively ketogenic?
  - Which are both ketogenic and glucogenic?

Answer

A

A ketogenic amino acid is degraded into:
- acetyl CoA or
- acetoacetyl CoA (ketone bodies)
- …through ketogenesis
The carbons of ketogenic amino acids are ultimately converted to CO₂ in the citric acid cycle
- because acetyl CoA carbons are converted to CO₂
Leucine and lysine are both ketogenic
Glucogenic amino acids can be converted to glucose
- …through gluconeogenesis
They are converted:
- first to alpha keto acids
- and then to glucose in the liver.
Some amino acids are both ketogenic and glucogenic:
1. isoleucine
2. phenylalanine
3. tryptophan
4. tyrosine
5. threonine
If you can remember those 5 and the 2 that are ketogenic, all the rest are glucogenic

Question 50

Q

Regulation of Carb Metabolism
- Allosteric Control
  - What role does the eventual target molecule have with regards upstream events?
  - What allosteric effect does ATP have on PFK-1?
  - What about AMP & ADP?

Answer

A

The eventual target molecule, or logical goal of the process, is often a major inhibitor that downregulates upstream production.
- For example,
  - ATP acts as an allosteric inhibitor of Phosphofructokinase-1 (PFK-1)
    - the enzyme for the rate-limiting step of glycolysis.
- That makes perfect logical sense!
  - When ATP levels are high the process will be downregulated.
- Meanwhile, AMP and ADP are allosteric activators of PFK-1

Question 51

Q

Gluconeogenesis
- Describe
- Where does it occur?
- When you see “Gluconeogenesis,”THINK???

Answer

A

Gluconeogenesis:
- Conceptualized as the reversal of glycolysis to produce:
  - glucose from pyruvate
- However, three glycolytic enzymes are substituted for four unique enzymes specific to gluconeogenesis
When you see gluconeogenesis, THINK:
- Gluconeogenesis = LIVER, fasting, and the need to increase blood sugar

Question 52

Q

When you see:

NADH/NAD⁺
NADPH/NADP⁺ (in PPP)
FADH₂/FAD
FMNH₂/FMN
semiquinone (an FMNH* radical)
ubiquinone ( aka “coenzyme Q/Q complex” in ETC)
cytochrome (also in ETC)

THINK: _______ RXNS

Answer

A

REDOX REACTIONS

These are soluble electron carriers
As they pass from one form to the other there is ALWAYS electron transfer
- and ∴ oxidation-reduction

Question 53

Q

Biochemical Shuttles
- Carnitine Shuttle
  - What is the Problem & Solution?

Answer

A

PROBLEM:
- Fatty acids cannot pass through the inner mitochondrial membrane
  - which is where they need to be in order to go through β-oxidation.
SOLUTION:
- The enzyme Carnitine acyltransferase attaches the fatty acyl group from an acyl-CoA to the OH^-group of carnitine.
- A translocase enzyme on the inner mitochondrial membrane moves one acyl-carnitine into the matrix and one carnitine back out

Question 54

Q

Fermentation (Anaerobic Glycolysis)
- What makes fermentation IMPORTANT??

Answer

A

Fermentation is IMPORTANT because it:

REGENERATES NAD⁺

so that glycolysis can continue!

NAD⁺ regeneration is necessary for both:
- human fermentation during oxygen debt
- and yeast/bacterial fermentation

Question 55

Q

ATP Synthase
- The translocation of a proton through the F₀ moiety of ATP synthase is associated with a very large negative ΔG
- Suppose a localized change in temperature decreased the free energy released by this reaction.
- What would be the likely effects on:
  - a) ATP production
  - b) ETC function
  - c) the strength of the electrochemical gradient
  - d) the Citric Acid Cycle
  - (Note: Assume other metabolic processes and enzymes do not experience the same temperature change.)

Answer

A

A decrease in the free energy released by a reaction will, in general, decrease the rate of the reaction.
In this case, decreasing the free energy released of translocating a proton through ATP synthase will:
- A) decrease ATP production
  - because the equilibrium will be shifted such that the phosphorylation of ADP to ATP will happen at a slower rate.
- B) Electron transport chain function will decrease
  - because there won’t be as many protons to pump out by Complexes I, III, and IV if they aren’t being pumped in at the same rate by ATP synthase.
  - ETC function will not decrease as much or as quickly as ATP production
    - because the enzymes involved are not directly affected by the free energy decrease.
- C) The electrochemical gradient will increase slightly
  - because protons will be pumped out by Complexes I, III, and IV, but ATP synthase won’t be pumping them back in as quickly.
- D) The citric acid cycle will still function normally
  - because it does not depend on ATP synthase

Question 56

Q

Lipid Metabolism
- β-Oxidation of FA’s
  - β-oxidation for ODD-NUMBERED fatty acids

Answer

A

Fatty acids with an odd number of carbons will result in a 3-carbon residue:
- propionyl-CoA
This reacts via multiple steps to form succinyl-CoA
- …which is then fed back into the Krebs Cycle
You do NOT need to memorize these names, just remember that with odd-chain fatty acids there is a leftover residue

Question 57

Q

Location Review
- Which metabolic substrates, enzymes, or products are “trapped” in a single cellular compartment?
- For example, are some found only in the cytosol?
- Are others trapped in the mitochondrial matrix and cannot leave?

Answer

A

In general, most metabolic substrates are able to move freely or be transported around the cell
Enzymes, however, are often “trapped” in one location
- Consider the enzymes of the ETC
  - All of them are membrane proteins, which means that they are always embedded in the inner mitochondrial membrane
- Also trapped within the mitochondrial membrane are the cofactors of the ETC
  - such as ubiquinone and cytochrome c
Glycolysis occurs in the cytoplasm
- as such, the enzymes for glycolysis are located in the cytoplasm.
The citric acid cycle occurs in the matrix of the mitochondria
- where the enzymes are “trapped”
The products of glycolysis and the citric acid cycle can be transported across the membrane and are not trapped.

Question 58

Q

Electron Transport Chain

What is the approximate number of protons pumped by each complex?
What is the approximate number of protons pumped by each:
- NADH molecule?
- FADH2 molecule?
How many protons are associated with the generation of one ATP at the ATP Synthase molecule?

Answer

A

Complex I

pumps 4 H⁺s

Complex II

pumps 0 H⁺s
- because it does not traverse the membrane, ∴ it can’t pump protons

Complex III

pumps 4 H⁺s

Complex IV

pumps 2 H⁺s

Utilizing electrons from an NADH molecule will result in 10 H⁺s pumped

because the electrons go through Complex I, III, and IV (So 4 + 4 + 2=10)

Utilizing electrons from FADH₂ will result in 6 H⁺s pumped

because the electrons go through Complex II, III, and IV (so 0 + 4 + 2=6).

To generate 1 ATP molecule at the ATP Synthase:

3 protons are needed

This means that every NADH generated will result in 3 ATPs
and every FADH₂ will generate 2 ATPs

Question 59

Q

Bioenergetics & Thermodynamics
- What do ATP and ADP look like?

Question 60

Q

Pyruvate Dehydrogenase Complex (PDC)
- Converts ___ to ___ using a set of # _____s
- Think of the PDH complex as?

Answer

A

Pyruvate⇒Acetyl-CoA

Think of the PDH complex as:
- the linkage between glycolysis and the Citric Acid Cycle
It is a set of three enzymes that convert pyruvate to acetyl-CoA
- which is the first substrate of the Citric Acid Cycle

Question 61

Q

Biochemical Shuttles

Glycerol-3-Phosphate Shuttle
- What is the Problem & Solution?

Answer

A

PROBLEM:

Same as with the Malate-Aspartate Shuttle

NADH can’t enter mitochondria to participate in ETC

SOLUTION:

NADH donates two electrons to DHAP
- to form G3P

G3P** is converted **back into DHAP

by MITOCHONDRIAL G3P*
…which is an enzyme bound to the cytosolic surface of the IMM

The G3PDH enzyme passes the electrons to FAD

to form FADH₂

Question 62

Q

Lipid Metabolism
- β-Oxidation
  - Draw a diagram showing the mechanism by which the carnitine shuttle moves fatty acids from the intermembrane space into the matrix of the mitochondria.
  - Include the following:
    - ATP
    - AMP
    - PPi
    - CoA
    - fattyacyl-CoA
    - fattyacyl-carnitine

Question 63

Q

Lipid Metabolism
- β-oxidation of fatty acids
  - Net Results of each 2-carbon cycle of β-oxidation results in?
  - Include how many ATP the above products yield

Answer

A

1 FADH₂
- =2 ATP
1 NADH
- =3 ATP
1 Acetyl-CoA
- =12 ATP

Question 64

Q

Fermentation (Anaerobic Glycolysis)

Ethanol vs. Lactic Acid Fermentation
- In each:
  - What does each route produce
  - What is the final electron acceptor?

What changes in Ethanol fermentation that doesnt change in Lactic Acid Ferm?

Answer

A

LACTIC ACID FERMENTATION:

LACTATE is produced
LACTATE is the final electron acceptor

ETHANOL FERMENTATION: (in yeast, a few bacteria)

ETHANOL is produced
ETHANOL is the final electron acceptor
Ethanol fermentation is unique compared to lactic acid fermentation in that:*
the CARBON SKELETON CHANGES!*

Pyruvate (3C) ⇒ethanol (2C) and CO₂

Answer 60

A

THINK:
- PPP=
  - 1) NADPH synthesis
  - 2) Ribose-5-Phosphate (R5-P)

Oxidative Phase
Non-Oxidative Phase

Answer 61

A

THE PHOSPHO-ANHYDRIDE BONDS*
(THAT CONNECT THE PHOSPHATES )***
are what make ATP an effective energy store for the cell*

This type of bond is *HIGHLY energetic*

At physiological pH, the phosphate groups lose their protons and become negatively charged

The negative charges repel one another
- and with 3 charged phosphate groups, there is a much greater repulsion occurring

Also, ADP and P_i are much MORE STABLE than ATP

due to less repulsion (less negative charges)
more resonance stabilization

Therefore the ΔG of converting ATP to ADP and Pi is very NEGATIVE

Answer 62

A

The Citric Acid Cycle is NOT oxidative phosphorylation
- NEITHER is the ETC
Those are PREPARATORY steps:
- to create the electrochemical gradient across the inner mitochondrial membrane
  - so that oxidative phosphorylation CAN occur

Answer 63

A

The four enzymes specific to gluconeogenesis replace three glycolytic enzymes which all catalyze PHOSPHORYLATION REACTIONS
- Those three steps that are replaced are all irreversible as well

Answer 64

A

Different tissues use different energy sources preferentially

Muscle: Differs by muscle type and duration of use

Cardiac
- Fatty acids during well-fed state
- Fatty acids and ketones if fasting
Skeletal
- Glucose during well-fed state
- Fatty acids and ketones if fasting

Answer 65

A

ATP⇒ADP + energy

Differs from Hydrolysis b/c:

The phosphate is transferred ONTO ANOTHER MOLECULE, rather than being released as P_i

EXAMPLE: Glucose + ATP ⇒Glucose-6-Phosphate + ADP
- (occurs during glycolysis)

Answer 66

A

VERY HIGH glucagon and epinephrine levels
VERY HIGH rate of gluconeogenesis
High rate of fatty acid oxidation
- resulting in:
  - ketone bodies &
  - acidosis

Answer 67

A

l) OUTER (!!!) mitochondrial membrane
m) mitochondrial matrix
- fatty acids are activated in the cytosol
- very long chain fatty acids are oxidized first in peroxisomes
- So you might find traces of radioactivity there, but the question asks for where it will be in abundance, which would be in the matrix
n) mitochondrial matrix
o) mitochondrial matrix of cells throughout the body during fasting or starvation,
- NEVER In the liver
  - it lacks the necessary enzymes
  - ketogenesis occurs only in the matrix of liver cells, though
p) cytosol
- primarily of liver cells
- to some extent in the kidneys
- NOTE:
  - This is ONLY true because we specified argininosuccinate, which is the product of a cytosolic enzyme that participates in the urea cycle.
  - Of the five enzymes in the urea cycle, two are mitochondrial and three are cytosolic
q) mitochondrial matrix
- from carbamoyl phosphate synthetase 1, one of the two mitochondrial urea cycle enzymes),
r) mitochondrial matrix AND the cytosol
- Matrix
  - is a product of the second mitochondrial urea cycle enzyme
- Ctyosol
  - citrulline is transported from the matrix to the cytosol
  - as part of the urea cycle
s) BOTH the mitochondrial matrix and the cytosol
- ornithine is transported from the cytosol to the mitochondrial matrix
  - …as part of the urea cycle
t) BOTH the cytosol and the matrix
- Matrix
  - malate is part of the TCA cycle (in the matrix)
- Cytosol
  - participates in the Citrate shuttle (in the cytosol)

Answer 68

A

Mnemonic:
- Girls
  - Glucose
- Get
  - Glucose-6-Phosphate
- Free
  - Fructose-6-Phosphate
- Food
  - Fructose 1,6-Bisphosphate
- Guys
  - Glyceraldehyde 3-Phosphate (G3P)
- Dont
  - Dihydroxyacetone Phosphate (DHAP)
- Boys
  - 1,3-Bisphosphoglycerate
- Prefer to
  - 3-Phosphoglycerate
- Pay for
  - 2-Phosphoglycerate
- Pricey
  - Phosphoenolpyruvate
- People
  - Pyruvate

Answer 69

A

Much as glycolysis and gluconeogenesis are reciprocally regulated, glycogenolysis and glycogen synthesis are regulated in opposite ways

Glycogenolysis

is the breakdown of glycogen into G6P
is stimulated by the presence of GLUCAGON and EPINEPHRINE in the bloodstream*

In both cases, the hormones stimulate a cAMP cascade

…which ultimately activates protein kinase A.
- This phosphorylates phophorylase kinase
  - which activates glycogen phosphorylase

Glycogenolysis is shut down when the stimulating HORMONES ARE GONE from the blood stream

Without the stimulating hormones, the cAMP cascade is withdrawn
- and protein phosphatase I dephosphorylates glycogen phosphorylase

Answer 70

A

ATP + H₂O ⇒ADP + P_i + energy
Note that inorganic phosphate (Pi) is created rather than a phosphate group being added to another molecule
ATP hydrolysis is almost always coupled to another reaction or process
- this is so that the free energy released can be utilized to drive another reaction or do work
  - (e.g., cocking the myosin head)

Answer 71

A

Shuttles are used to TRANSPORT MOLECULES across impermeable membranes.
- In some cases, the molecule is simply activated by adding a functional group that increases its solubility.
- In other cases, only a portion of the membrane-impermeable parent molecule (such as functional group) is passed through the membrane.
- Sometimes, only electrons are passed through the membrane and the entire parent molecule remains outside.

Answer 72

A

These thyroid hormones increase BASAL metabolic rate
Both are secreted by the thyroid
- in response to TSH from the anterior pituitary

Answer 73

A

It may be said that Drug X “uncouples” the ETC or the electrochemical gradient from oxidative phosphorylation.
- This means the gradient is no longer directly driving ATP production at the ATP synthase.
  - For example, this could be because a drug inserted proton channels into the inner mitochondrial membrane.
  - The ETC would continue to pump protons, but because protons have an alternate route back into the matrix, the two processes would no longer be directly or fully “coupled.”

Answer 74

A

Fatty-Acid Synthesis:

LOCATION:
- Occurs primarily in the cytosol of liver cells
Fatty-Acid synthesis is always the construction of 16-carbon palmitic acid
- the only fatty acid the human body can synthesize from scratch
  - This occurs in the cytosol
Other forms of lipid synthesis (such as synthesis of phospholipids and steroids)
- occurs on the smooth ER
Acetyl-CoA come from the mitochondria, but get THROUGH the cytosol via…
- the Citrate Shuttle

Answer 75

A

Refers to the process of allosteric regulators binding to enzymes to either:
- upregulate or
- downregulate their activity.
Allosteric effects almost always result from conformational changes
Allosteric regulator molecules always binds AWAY FROM THE ACTIVE SITE.
- In other words, the effect is a change in the enzyme itself…
  - NOT inhibition by competing with the substrate for the active site

Answer 76

A

Ketogenesis

Is the process by which ketone bodies are produced
- through the breakdown of fatty acids

This occurs in the liver

This occurs during periods of starvation
- when blood glucose levels drop
- And no further source of carbohydrate fuel is available.
Ketogenesis is able to provide energy
- by generating acetyl CoA to be fed into the citric acid cycle

Ketolysis

is the utilization of ketone bodies for ENERGY
- by converting them to acetyl CoA for energy
This occurs in organs OTHER than the liver
- mainly the heart and brain

The liver is LACKING an essential enzyme for the utilization of ketone bodies for energy

When blood glucose is low:

β-oxidation and
ketogenesis occur in the liver
Ketone bodies are transported out of the liver to key tissues
- where they can be used for energy through ketolysis
The brain (and CNS) in particular relies on ketone bodies when glucose is not abundant.
Most other tissues and organs can use fatty acids for energy when glucose is low, but…

The CNS relies on GLUCOSE primarily, and KETONE bodies during periods of starvation

Answer 77

A

Each NADH=
- 3 ATP
Each FADH₂=
- 2 ATP

Answer 78

A

Feeder Pathways:
These other pathways funnel into glycolysis

MAIN PATHWAY: Glycogen Metabolism

Glycogen =
- glucose polymer
- Mostly in Liver (also high in muscle)

Glycogen phosphorylase:
- removes glucose residues from the reducing ends of glycogen polymers
  - Glycogen⇒Glucose-1P
Phosphoglucomutase:
- converts Glucose-1P ⇒Glucose-6P
  - (2^nd step of GLY)

Answer 79

A

Equilibrium is NOT the same as a steady state!
Equilibrium:
- is a dynamic state existing at the lowest possible entropy and energy for that system.
  - If you were at complete equilibrium with your environment, you would be dead!!
Living systems must constantly invest energy to maintain a steady homeostatic state
- …that is FAR away from equilibrium!!

Answer 80

A

Proton Motive Force
- The driving force of the electrochemical gradient established by the electron transport chain that is harvested by ATP synthase to produce ATP
- The energy released as protons move:
  - down their concentration gradient AND
  - down their electrical gradient toward the mitochondrial matrix
  - …is used by ATP synthase to add a free organic phosphate to ADP
    - thus creating ATP

Answer 81

A

ΔG ≠ ΔG°’
ΔG°’ is dependent on the concentrations of reactants and products
ΔG is not dependent on the concentrations of the reactants or products
ΔG°’ can be considered for any point of a reaction, not just the end point

Answer 82

A

Metabolic regulation often involves a downstream product inhibiting an upstream enzyme
- That makes perfect sense because the first few product molecules synthesized are very unlikely to immediately interact with the enzyme—meaning it won’t be shut off too early
However, as that product builds up, the upstream enzyme will begin to interact with that product frequently, and the enzyme will be inhibited.
- In this way production is slowed only after the necessary amount of a biomolecule has been produced.

Answer 83

A

ATP Synthase is where oxidative phosphorylation occurs
Oxidative phosphorylation
- is the phosphorylation of ADP, using:
  - energy from the gradient (created by CAC & ETC)
  - and oxygen as the FINAL ELECTRON ACCEPTOR

Answer 84

A

The citric acid cycle is tightly regulated
- because without regulation, large amounts of NADH and ATP could be wasted
The PDH complex, the entry point to the CAC, is inhibited by its products
- acetyl CoA and NADH.
PDH is also inhibited by:
- phosphorylation stimulated by high levels of NADH and ATP
When NADH and ATP are low, PDH is dephosphorylated and activated.
The citric acid cycle itself is regulated at many points.
Isocitrate dehydrogenase
- stimulated by ADP
- inhibited by ATP and NADH.
α-ketoglutarate dehydrogenase
- inhibited by its products
  - succinyl CoA and NADH
- also inhibited by ATP

Answer 85

A

Fat

9 k_cal/g

Protein

4 k_cal/g

Carbohydrate

4 k_cal/g

Answer 86

A

MUSCLE & KIDNEYS:

Hexokinase converts:
- Fructose⇒Fructose-6P (F6P)

⇒3^rd step of glycolysis

(gets converted into F1,6BP by PFK-1)

Answer 87

A

Cause ketoacidosis
- or excess acidity of the blood.
Diabetes can also cause ketoacidosis
- because a lack of insulin available for sugar uptake from the blood forces the liver to switch to fatty acid metabolism almost as if the person were fasting

Answer 88

A

ETC

Stimulated by
- high levels of ADP and
inhibited by
- high levels of ATP.
Additionally, there are many POISINS that inhibit ETC
- Rotenone (an insecticide),
  - blocks electron transfer in NADH-Q oxidoreductase
- Cyanide, azide, and carbon monoxide
  - block electron flow in cytochrome c oxidase
- Oligomycin (an antifungal agent),
  - prevents proton flow through ATP synthase

Answer 89

A

Process:
- Carbons are removed two at a time to form Acetyl-CoA
  - which is then fed into the Citric Acid Cycle
REQUIRES (per 2-carbon cycle):
- 1 FAD
- 1 H₂O
- 1 NAD⁺
- 1 CoA-SH
Note:
- An activated fatty acid will already have an –S-CoA group on the carbonyl end of the chain.
- The CoA-SH required here is added to the 2-carbon acetyl group that is the product of the oxidation,
  - thus creating an Acetyl-CoA rather than acetic acid

Answer 90

A

High glucagon levels; low insulin levels
Higher relative rate of catabolism (vs. anabolism; reversal of the well-fed state)
Glycogenolysis = Immediate increase
Gluconeogenesis = Delayed increase (~12 hrs)

Answer 91

A

Anabolism is the opposite of catabolism
- is more often referred to as “synthesis”
Anabolic processes
- Construct macromolecules out of smaller precursors
Catabolic processes
- Break down macromolecules into smaller precursors or monomeric units

We have already discussed glycogen synthesis because it is an integral part of Glucose metabolism

The body also synthesizes fats and carbohydrates

Answer 92

A

Chemiosmotic Coupling
- The direct coupling of the energy inherent in the electrochemical gradient across the inner mitochondrial membrane to the phosphorylation of ADP
  - …to form ATP

Answer 93

A

Dephosphorylation can also turn a molecule on or off, but it does not usually result in the re-formation of ATP.
Phosphorylation and dephosphorylation are opposite regulatory functions, but they are NOT a reversal of the same reaction
Phosphorylation uses:
- protein kinases and ATP
dephosphorylation uses:
- phosphatases and produces free P_i

Answer 94

A

3 Destinations:
1. PDH Complex⇒Acetyl-CoA
  - (Feeds into the Citric Acid Cycle)
2. Lactate Dehydrogenase⇒Lactate
  - (Fermentation)
3. Pyruvate Carboxylase⇒Oxaloacetate
  1. (1st step of gluconeogenesis)

Answer 95

A

PROBLEM:
- NADH cannot pass through the inner mitochondrial membrane :(
  - ∴, NADH produced from glycolysis can’t enter the ETC without this shuttle
SOLUTION:
- NADH donates two electrons to oxaloacetate (OAA), converting it to malate.
  - Malate passes into the matrix
    - via the MALATE-α-KETOGLUTARATE ANTIPORTER.
  - Inside the matrix, malate is converted back into OAA
    - regenerating NADH
  - OAA is then converted into asparate
    - so that it can be pumped back into the cytosol
      - via the GULATAMATE-ASPARTATE SHUTTLE.

Answer 96

A

Galactose Metabolism:
- The entire pathway is a bit too complex for the scope of the MCAT
- Focus on the following:
  - In multiple steps:
    - Galactose is converted ⇒Glucose-1P
    - (UDP = coenzyme)
  - Phosphoglucomutase converts:
    - Glucose-1P⇒Glucose-6P (2nd step GLY)

Answer 97

A

Primary sugar in many fruits
Also a product of sucrose hydrolysis

Answer 98

A

Substrate level phosphorylation
- is the process by which a phosphate group is transferred to ADP or GDP from a phosphorylated intermediate.
  - The Citric Acid Cycle uses substrate level phosphorylation.
Oxidative phosphorylation
- occurs in ATP synthase in the electron transport chain.
- This process combines ADP and inorganic phosphate to generate ATP
  - …through the generation of a proton gradient by transporting electrons

Answer 99

A

NADPH is an important REDUCING AGENT used during “Reductive Biosynthesis”
- —a general term referring to a large number of reactions used to synthesize fatty acids and sterols.
NADPH is also necessary for :the production of Glutathione
- which is the most important antioxidant
  - which counteracts the damaging impact of:
    - the peroxide and
    - radical byproducts of oxidative respiration

Answer 100

A

A) False
- ΔG° can be calculated if K_eq is known
B) False
- ΔG can be calculated if K_eq is known
C) True
- If K_eq = Q, the reaction is at equilibrium, and ΔG = 0
D) False
- The reaction is at equilibrium
- …but ΔG° is not 0 at equilibrium
E) True
- If K_eq is greater than 1, the reaction will favor the products and ΔG°’ will be negative.
F) True
- For the same reason E is true^

Answer 101

A

R5-P is used to:
- synthesize nucleotides
It is the oxygen-bearing ring of all nucleotides
- including the famous DNA
The “5” in R5-P refers to the 5’ carbon

Answer 102

A

Phosphorylation using ATP =
- Major Human Body Regulatory Mechanism
  - Many enzymes, proteins, and signaling molecules are turned “on” or “off” by the process of phosphorylation via a phosphoryl group transfer
ATP acts as the donor of the phosphate group needed for phosphorylation
Protein Kinases are the enzymes that catalyze phosphorylation coupled to ATP cleavage
EXAMPLE: Glycogen Phosphorylase-A (GPA) is the enzyme that catalyzes the breakdown of glycogen to glucose:
- GPA^# + 2ATP ⇒GPA-PP** + 2ADP
  - ** = active
  - # = inactive

Answer 103

A

The most likely step to be regulated in a metabolic pathway is the first non-reversible reaction step
If the pathway has multiple ALTERNATIVE pathways, it is usually the first irreversible step AFTER which the molecule is COMMITED to finishing the pathway

For example, the first non-reversible step in glycolysis is *hexokinase*

However, Glucose-6-P has possible alternative fates other than completing glycolysis
- (e.g., glycogen synthesis, PPP)

The NEXT irreversible step is catalyzed by PFK-1 *(very highly regulated!!!)*

After this step, all molecules will complete glycolysis
- And it is thus the main regulatory point for glycolysis

Answer 104

A

Most amino acids can be broken down into either pyruvate or acetyl-CoA
- and fed into the Citric Acid Cycle
The remaining amino acids can be transformed into various other Citric Acid Cycle intermediates
- often alpha-ketoglutarate
- Step and enter into the cycle at the appropriate point.
Notice that we have now seen that the pyruvate/acetyl-CoA that feed into the Krebs cycle can be derived from:
1. carbohydrates
2. fats, or
3. proteins

Answer 105

A

a) cytosol
b) mitochondrial matrix
c) cytosol
d) mitochondrial matrix
e) cytosol
f) cytosol
- primarily of liver cells
- in kidney cortex cells (to a lesser degree)
g) mitochondrial matrix of liver cells/some kidney cells
- NOTE: First, pyruvate carboxylase converts oxaloacetate to pyruvate in the matrix, gluconeogenesiss then continues in the cytosol
h) cytosol—primarily of liver cells
i) mitochondrial matrix,
j) inner mitochondrial membrane (part of the ETC)
k) inner mitochondrial membrane

Answer 106

A

Adenosine Triphosphate (ATP)
ATP = The primary energy currency of the human body
ΔG°’ for ATP hydrolysis
Sequential loss of one phosphate group changes ATP⇒ADP ⇒AMP
Cyclization takes AMP⇒cAMP
- You’ll want to be familiar with cAMP because it is the most common second messenger molecule encountered on the MCAT
The ATP⇒ADP⇒AMP transitions all have a negative ΔG°’
- are ∴ exergonic
The AMP⇒cAMP transition is endergonic.
- Surprisingly, cAMP is actually a higher-energy molecule than ATP

Answer 107

A

ΔG°, or standard free energy, is the ΔG of a reaction at “standard” conditions, when each reactant is at a concentration of 1.0 M.
- In the body, this is almost never the case
Further, reactions in the body are typically at near-equilibrium, when ΔG is very close to 0.
- ΔG° of a single reaction in the body is typically not very useful, as reactions are often coupled or regulated in some way such that something may appear to be non-spontaneous, but in the body it occurs spontaneously

Answer 108

A

ΔG°’ = -RTlnK_eq
At equilibrium:
- Q = K_eq
- ΔG = 0
Starting with ΔG = ΔG°’ + RTlnQ we have:
- ΔG = ΔG°’ + RTlnK_eq and
- 0 = ΔG°’ + RTlnK_eq
Subtracting “RTlnK_eq” from both sides, we get:
- ΔG°’ = -RTlnK_eq

Answer 109

A

Acetyl CoA= The FIRST substrate of the Citric Acid Cycle

CARBOHYDRATE ORIGIN:
- glycolysis⇒pyruvate⇒Acetyl-CoA
  - …..by the PDH Complex
LIPID ORIGIN:
- β-oxidation of fatty acids
PROTEIN ORIGIN:
- amino acid metabolism

Answer 110

A

Rounds of β-oxidation is required to oxidize an even numbered fatty acid:
1. simply divide the number of carbons by 2
2. subtract 1.
So for a 14-carbon fatty acid, 6 rounds of β-oxidation are needed.
This is because every round cleaves 2 carbons off
- At the end, a final round cleaves the 4-carbon fatty acid into two 2-carbon fatty acids,
  - finishing the oxidation.
Rounds of β-oxidation is required to oxidize an odd numbered fatty acid:

subtract 1
- to get to an even number
Then divide by 2, and
subtract 1

So for a 17-carbon fatty acid, 7 rounds of β-oxidation are needed (17-1=16. 16/2=8. 8-1=7).
This is because every round cleaves off two carbons, but at the end of an odd numbered fatty acid, the final round cleaves the 5-carbon fatty acid into one 2-carbon fatty acid and one 3- carbon fatty acid

Answer 111

A

A) True
- Reaction X, ΔG = -30.78 kJ
- Reaction Y, ΔG = 22.5
- ∴ Reaction Y is closer to equilibrium.
B) False
- ΔG°’ = 0 does not represent equilibrium
- At equilibrium, ΔG°’=-RT ln[C][D]/[A][B]
  - because ΔG=ΔG°’+RT ln[C][D]/[A][B]
- At equilibrium, ΔG = 0
C) True
- ΔG = 0 at equilibrium
D) True
- ΔG°’ is dependent on the concentrations of reactants and products.
E) False
- ΔG is not dependent on the concentrations of the reactants or products
F) False
- ΔG°’ can be considered for any point of a reaction, not just the end point

Answer 112

A

NON-OXIDATIVE PHASE:

Rib**ulose**-5-Phosphate ⇔ SUGAR POOL ⇔ Glucose-6-Phosphate
- SUGAR POOL =
  - Erythrose-4-P
  - Sedoheptulose-4-P
  - Xylulose-5-P, and
  - A number of other carbohydrates you do NOT need to know for the MCAT
KNOW THIS:
1. That…
  - Conversion into the SUGAR POOL from Ribulose-5-Phosphate
  - interconversions between sugars within the pool, and
  - conversion to Glucose-6-P
  - are all catalyzed by either :
    - Transketolase or
    - Transaldolase
2. All of the reactions into, out of, and inside of the pool are REVERSIBLE

Answer 113

A

CREATINE PHOSPHATE is a very-short-lived energy source for short bursts of action
FATTY ACIDS for very prolonged exercise (i.e., endurance athletes like Dad)

The *MAIN FUEL* is:

GLUCOSE from the glycogen stores
- switching from oxidative use of glucose to lactic acid fermentation during prolonged exercise
if exercise continues even longer
- … the muscles must use only fatty acids!!!

Answer 114

A

LIPIDS

metabolized in

the mitochondria

synthesized in

in the cytosol
- (mostly hepatocytes)

modified in

the SER

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