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Lecture 22: Cellular Metabolic Pathways and ATP
Terms in this set (13)
What are some reasons why phosphate groups are so important for cellular functions involving energy and control of protein function?
Regulate protein function
→ Often transferred (such as from ATP) as a way to regulate substrate function
Understand the difference between a kinase and a phosphatase.
Kinase: Enzymes that transfer PO4- to targets (phosphorylation)
Phosphatases: Enzymes that remove the PO4- group from target
Review the concept of cellular metabolism being the combination of anabolic and catabolic pathways.
How do the terms endergonic and exergonic apply?
When relating complex molecules to simpler molecules that compose them, how does the concept of ΔG fit in?
What about highly reduced molecules versus highly oxidized
Anabolism: Creation of complex molecules
→ Endergonic: +ΔG and energy has gone into the system
Catabolism: Break down of molecules into simpler ones
→ Exergonic: -ΔG and energy has been released by the system
Oxidized to Reduced: +ΔG → Endergonic
Reduced to Oxidized: -ΔG → Exergonic
Understand that glucose is the main fuel source for cells, but its energy potential (C-C) bonds must be converted into ATP to be distributed and widely used in cellular pathways
(consider the analogy of burning coal to make electricity, and how being given a lump of coal to recharge your phone is pretty useless).
Energy from glucose must be converted into a more convenient molecular form (ATP) that energy-requiring processes in the cell are designed to use.
Ex. Fuel source is coal and it goes into a coal factory → transformed into energy output (electricity) → changed into more convenient form to use
Look at the molecular model of glucose compared to ATP. Recall that glucose has potential energy of -686 kcal/mol when oxidized down to CO2 and H2O whereas the terminal (3rd) phosphate bond of ATP yields -7.3 kcal/mol when broken. ATP doesn't seem very impressive at first glance, does it? Then consider the amount of energy being released by a burning pile of coal, and how only a tiny bit of that energy actually flows through your USB phone charger. Likewise, ATP is a very controlled way to distribute the energy of glucose oxidization throughout the cell where needed (i.e. a large amount of energy spread around in small packets).
Glucose is a large, uncontrolled packet of energy → like coal when burned straight all the energy is released at once
ATP comes in smaller, controlled packets of energy → like small amounts of electricity running through charger that charge your phone.
Look at the molecular structure of ATP, and think about how this is really an adenosine ribo-nucleotide with extra phosphate groups. This is another wonderful example of how evolution found ways of using the same molecule for different functions (Nucleic acids = information storage, ATP = energy flow...using pretty much the same base+sugar+phosphate theme!)
ATP: Adenosine Ribo-Nucleotide with (2) extra phosphate groups
Nature uses the same molecule but with a different number of phosphate groups/base groups for different functions
Understand that the energy released by breaking of high-energy C-C glucose bonds allows for forming the terminal phosphoanhydride (3rd phosphate group) bond of ATP.
Therefore ATP "carries around" that bit of energy from glucose until interactions with another molecule (such as an enzyme) breaks that bond to do work (synthetic, concentration gradient, electrical, mechanical, bioluminescent, etc.).
ATP makes energy portable around cell
Since ATP is carrying around a small "packet" of the energy from glucose catabolism, often the analogy of ATP as money or currency is used. Just as with favorable or unfavorable exchange rates of international money, we can think that the ATP is "worth" some amount of energy, and therefore 1 ATP can be converted into many "lower value" currency (you can drive creation of lower-energy bonds) but 1 ATP cannot be exchanged for 1 "higher value" currency (you cannot drive creation of a higher-energy bond). Of course, just with money you could spend multiple ATP molecules to afford the higher-priced molecular bond. These money analogies get us thinking about how the thriving "business economy" of molecular pathways in our cells are designed to be powered by a standard energy unit ATP.
Understand that the oxidation of biological molecules is exergonic, and involves the removal of 2 paired e- and H+ (the equivalent of 2 hydrogen atoms).
However, also keep in mind these aren't simply 2H that go flying off somewhere, but rather are being simultaneously transferred to a recipient molecule (that is being reduced). That is why we write the [H2] in brackets.
Biological molecules are highly exergonic
Dehydrogenation: pair of e- and pair of H+ removed
Understand that it wouldn't make sense for enzymes working on oxidizing a target molecule to necessarily accept the e- themselves, since that would change their property, and they'd have to be "reset" (themselves oxidized) as the substrate of another enzyme. That would NOT be very inefficient. So small co-enzyme molecules such as NAD+ are used as electron acceptors (and are reduced to NADH). Thus, there only needs to be a system for resetting the NADH back to NAD+ which is far more efficient.
It's not efficient to have complex enzymes being reduced and then having to be reset to act again, so what's a better solution?
→ Enzymes often use another small molecule as the e- acceptor
Understand that NAD is basically two nucleotides joined at their phosphate group (but notice they are NOT connected in the same way as a nucleic acid backbone...can you spot the difference?)
Two nucleotides joined at their phosphate group connected by phosphate Os. Not phosphate to carbon.
Look at the structure of Vitamin B3. In the context of enzymatic pathways, do you now appreciate why vitamins are so important for proper health of our cells?
Every part of our body needs niacin to function
Understand the example of alcohol metabolism in terms of the oxidation of ethanol being a tightly controlled process requiring multiple enzyme steps and intermediate metabolites.
What role does the co-enzyme NAD+ play in this? Since the ADH and ALDH enzymes are proteins, consider how genetic variations in the coding amino acid sequence of these proteins could affect the ethanol catabolic pathway.
ADH converts ethanol to acetaldehyde, which is more toxic
Aldehyde Dehydrogenase (ALDH) quickly converts CH3CHO to acetate
Acetate is processed and becomes CO2 and H2O
ADH facilitates reduction of NAD+ to NADH for supply to the body
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