Lecture 11: Intro to Fuel Metabolism Flashcards
What part of ATP has a huge amount of energy?
The gamma (3rd) phosphoanhydride linkage to phosphate group
What is the difference between a nucleoside and a nucleotide?
Nucleoside = ribose + base (adenosine)
Nucleotide = ribose + base + phosphate (adenine)
What is adenosine made of?
Ribose + base = nucleoside
Why does ATP release the gamma phosphate?
Because it is thermodynamically SUPER favorable: entropically and enthalpically (exothermic)
Through what mechanism does ATP release the gamma phosphate?
SN2 nucleophilic substitution through attack by strong Nu (eg: deprotonated sugar)
Equation to calculate Gibbs free energy?
ΔG = ΔH - TΔS
What molecules are released when the alpha phosphate of ATP is attacked? What immediately happens to one of the products once released? How does this affect the reaction? What is this reaction called?
AMP-Nu + pyrophosphate
PPi degraded by pyrophosphatase (P-P linkage cleaved) so the reverse reaction cannot happen
→ Adenylyl transfer
How is energy literally transferred to make ATP?
High energy electrons on H atoms are transferred to oxygens in redox reactions breaking down macromolecules
How does free energy change throughout the ETC? Why?
How is entropy changing? Enthalpy?
Free energy decreases and is released and used to pump H+ outside of the mito matrix
- Entropy is decreasing (against the proton gradient)
- Enthalpy is increasing and driving the process until it can no longer compensate for the decrease in entropy (this is only theoretical because H+ flow back to matrix through F0)
Explain how a combustion reaction works. What are the products?
Glucose or H2 gives its hydrogens/electrons to O2 through a series of redox reactions and each step creates a mini explosion = releases energy = exothermic
Products: CO2 (g) + H2O (g)
What is NAD+ composed of? 3 parts
2 nucleotides: 1. Adenylate nucleotide (AMP moiety) 2. Nicotinimide nucleotide
2 phosphates
2 sugars
Which nucleotide of NAD+ is involved in carrying electrons?
Nicotinimide nucleotide
Difference in functions between NAD+ and NADPH?
- NAD+: coenzyme that is reduced in catabolic reactions
- NADPH: coenzyme that is oxidized in anabolic reactions
Is NAD+ a reducing or oxidizing agent?
Oxidizing
Is NADPH a reducing or oxidizing agent?
Reducing
How does the structure of NADP+ compare to NAD+?
NADP+ has a phosphate on the 2’ C of the adenylate nucleotide instead of an -OH
What are the 2 ways in which glucose can be used to produce ATP?
- Aerobically through oxidative phosphorylation 2. Anaerobically through fermentation
Does glucose oxidation happen in fermentation?
NOPE
How can the fuel from fat be used?
Aerobically through oxidative phosphorylation
How do we make macromolecules?
- ATP and NADPH produced during catabolism using NAD+
- ATP and NADPH used to carry out biosynthetic reactions
What are the products when carbs are used aerobically?
CO2 and water
Why do we have both NAD+ and NADPH?
So that the electron pools are separated and enzymes on either side can do their jobs independently and at a consistent speed: OPTIMAL NAD+/NADH ratio for catabolic and anabolic enzymes
What is the outer membrane of the mito permeable to? Through what?
Freely permeable to small molecules and ions passing through porin channels
What is the inner membrane of the mito permeable to?
Impermeable to most small molecules and ions, including H+
What does the mito inner membrane contain? 4 elements
- Respiratory electron carriers (complexes 1-4) 2. ADP-ATP translocase 3. ATP synthase (F0F1) 4. Other membrane transporters
What does the matrix of the mito contain? elements
- Pyruvate dehydrogenase complex 2. Citric acid cycle enzymes 3. Fatty acid beta-oxidation enzymes 4. Amino acid oxidation enzymes 5. Many other enzymes 6. DNA/ribosomes 7. ATP, ADP, Pi, Mg2+, Ca2+, K+ 8. Many soluble metabolic intermediates
How does the mito contribute to anabolism? How?
Provides intermediates for anabolism via export to the cytosol
What are alpha keto acids? What is their purpose?
AAs without the amino group (replaced by another carboxyl group) that will feed into other pathways
What is pyruvate? 2 answers
- The end product of glycolysis 2. The alpha keto acid of alanine
Draw alpha-keto glutarate.
Draw alpha-keto alanine aka pyruvate.
Draw alpha-keto aspartate aka oxaloacetate.
What other purine/pyrimidine bases can be used to make nucleotide triphosphates?
- Guanine
- Uracil
To what end of the adenosine are phosphate groups added?
5’
What kind of intermediate does the SN2 reaction of ATP hydrolysis involve?
Pentacovalent transition intermediate
Describe the energy transfer during the SN2 nucleophilic substitution.
The energy used to make the X-P bond is transferred to create the Y-P bond, but those 2 energies are rarely equal:
- If EX-P > EY-P → additional energy is released as heat and used to drive the rxn forward toward completion even when the transition state is surpassed and entropy is decreasing
- If EX-P < EY-P → more energy will be needed from the surroundings, so the rxn will only proceed if the entropy is increasing
What molecules are released when the gamma phosphate of ATP is attacked? What is this reaction called?
ADP + phosphate-Nu
→ Phosphoryl transfer
What molecules are released when the beta phosphate of ATP is attacked? What is this reaction called?
AMP + pyrophosphate-Nu
→ Pyrophosphoryl transfer
What limits the rxn that reduces NAD⁺ to NADH?
Acidic conditions
What does the production of ATP using FA rely on?
O2
How do plants produce metabolic fuels?
- Use energy from the sun to impart energy to Hs (H2O) to make ATP and NADPH and release O2
- Then used to make carbs by reducing CO2
List the 4 steps of the ATP generation process with products and a location for each.
- Anaerobic catabolism of glucose → ATP + pyruvate (cytosol)
- Pyruvate → Acetyl-CoA (mito)
- Krebs cycle → NADH + FADH2 + GTP (mito)
- ETC → ATP + H2O (inner membrane of mito)
What type of bond connects adenosine to the phosphate groups?
Phosphoester bond
What are the 2 purines?
Adenine and Guanine
What are the 3 pyrimidines?
- Cytosine
- Thymine
- Uracil
Which steps in metabolic pathways usually have large (-) ΔH values?
First/regulated steps
How many electrons can NAD+ accept?
2
Can enzymes use both NAD+ and NADP+?
Usually not
Should the NADP+/NADPH ratio be high or low when the body is trying to be biosynthetically active?
Low
Should the NAD+/NADH ratio be high or low when the body is trying to accelerate catabolism?
High
Why do we say the mito is self-propagating?
It has its own DNA and ribosomes
What is the official name of the cytosol of the mito?
Mitosol
What is the mito’s role in breakdown of AAs?
It collects nitrogens and C-skeletons = alpha-keto acids
Explain how entropy and enthalpy change during a reaction.
- Enthalpy usually increases and drives the reaction forward
- Entropy decreases as the molecule grows and becomes more specific (decrease in number of atoms = increase in entropy)
⇒ Increase in enthalpy usually overshadows the decrease in entropy for reactions to take place
What is the energy from ATP derived from?
Unfavorable orbital overlap and negative charges in close proximity
Photosynthesis: where does the carbon of carbs produced come from? Where do the Hs come from?
C: from CO2
H: from water
