Lecture 16 Metabolic Energy: Generation and storage Flashcards
How complicated are metabolic reactions?
Although metabolic reactions may look complicated the number of kinds of reaction is small and metabolic pathways are regulated in very similar ways
When can a thermodynamically unfavorable reaction take place?
- A Thermodynamically Unfavourable Reaction Can Be
Driven By A Favourable one - A reaction can occur spontaneously only if ΔG (the change in free energy) is negative ( -ΔG )
-However the overall free-energy change for a coupled series of reactions is the SUM of the free-energy changes of the individual steps - So a thermodynamically favourable reaction (-ΔG) can drive a thermodynamically unfavourable reaction (+ΔG) coupled to it
How can a thermodynamically unfavourable reaction be coupled with a thermodynamically favorable one?
There are three ways in which the reactions can be coupled:
-A shared chemical intermediate (Eg: glycolysis and substrate level phosphorylation)
-An activated protein conformation (Eg: molecular motors )
-Ionic (electrochemical) gradients across membranes
(Eg: oxidative phosphorylation)
What Is Energy Required For in an organism?
Motion:
- Active transport of solutes across membranes against their concentration and/or charge gradient
- Biosynthesis
- Signal Amplification
What Is Energy in an organism Obtained From?
- Oxidation of foodstuffs (chemotrophs)
- Trapping light energy (phototrophs)
- Part of this obtained energy is changed into (stored as) a highly accessible form before it is used
\+ This store in most energy-requiring systems is Adenosine Triphosphate (ATP)
What is ATP and what does it consist of?
- ATP is an energy rich molecule
-It is an energy carrier containing two
PHOSPHOANHYDRIDE BONDS
-A large amount of energy (~ΔG -12kcal/mol) is released when ATP is hydrolysed to ADP and phosphate (Pi) and exactly the same is stored when ATP is synthesised
=So the cycling between ATP and ADP is the fundamental mode of energy exchange in biological systems the ENERGY CURRENCY
How long does ATP store energy for?
- ATP Is Continuously Formed And Consumed
- ATP is NOT as a long term store
- A typical cell consumes ATP within ONE minute of its formation therefore turnover of ATP is very high
+ A resting human consumes ~40 kg of ATP/24 hrs
- ATP is an example of an ACTIVATED CARRIER
- The group carried is the phosphoryl group+ATP does NOT have special bonds, other than that large amounts of energy are released when they are hydrolysed under cellular conditions
What are some other activated carriers?
-NADH and FADH2 are further examples of Activated
Carriers
-These two molecules are the major electron carriers in the oxidation of fuel molecules
How do chemotrophs derive energy?
-Chemotrophs derive free energy from oxidation of fuel molecules, such as glucose and fatty acids
How does oxygen accept electrons in aerobic organisms?
- In aerobic organisms the ultimate electron acceptor is oxygen, BUT
- The electrons from the fuel molecules are NOT transferred directly to oxygen, but are instead transferred to special electron carriers:
- Pyridine nucleotides (i.e. NADH )
- Or flavins (FADH2)
- These reduced electron carriers then transfer their electrons to oxygen via an electron transport chain located in the inner mitochondrial membrane (IMM)
- The energy released is used to synthesise ATP (a process known as oxidative phosphorylation)
How does the electron acceptor NAD+ work?
-Nicotinamide adenine dinucleotide (NAD+ is a major electron acceptor in the oxidation of fuel molecules
-In the oxidation of a substrate NAD+accepts an H+ and two e, (equivalent to a hydride ion, H- ), to form NADH
+ NADH is used primarily for the generation of ATP
-The reduced form of NADP+ is NADPH, used almost exclusively for biosynthesis
-This needs reducing power in addition to ATP
Which is the other major electron carrier in the oxidation of fuel and how does it work?
- The other major electron carrier in the oxidation of fuel molecules is flavin adenine dinucleotide (FAD)
- The reactive part of FAD is the isoalloxazine ring, this accepts two e and two H+ (equivalent to two
hydrogens) to form FADH(2)
Why are enzymes necessary in these processes?
- NADH, NADPH and FADH(2) are slow to react with oxygen and ATP is only slowly hydrolysed
- Catalysts (enzymes) are required to speed these processes
- So these enzymes can control the flow of free energy and reductive power
Why are activated carriers important?
-Most interchanges of activated groups in metabolism are accomplished by a rather small set of carriers
What are the stages In The Extraction Of Energy From Foodstuffs?
-Hans Krebs described three stages in the extraction of energy from foodstuffs:
STAGE 1:
- Large molecules of food broken into smaller units
- Proteins to amino acids
-Polysaccharides to simple sugars (eg. glucose)
-Fats to glycerol and fatty acids
+ No useful energy is generated in this stage
STAGE 2:
-These numerous small molecules are degraded to a few simple units that play a central role in metabolism
-Most are converted to acetyl CoA
+Some ATP is generated at this stage
STAGE 3:
-Citric acid cycle and oxidative phosphorylation
+ 90% of ATP is generated in this last stage
How are metabolic pathways regulated?
Metabolic Pathways Are Regulated In
Three Principal Ways:
By controlling:
-The amounts of enzymes
+Amount depends on rate of synthesis and rate of breakdown
+The amount of most enzymes is regulated primarily by adjusting the rate of transcription of genes encoding them
-The catalytic activities of these enzymes
+Controlled in several ways
a) Reversible allosteric control
b) Reversible covalent modification
-The accessibility of substrates
+ For example by controlling their entry into the cell
What is an important general principle of metabolism?
An important general principle of metabolism is:
-Biosynthetic and Degradative pathways are
almost always distinct NOT THE SAME
-Many reactions in metabolism are controlled by the ENERGY STATUS of the cell
-One measure of the energy status of the cell
is the balance between concentrations of ATP
and AMP within the cell, known as the ENERGY CHARGE
What is the formula for energy charge?
([ATP] + 1/2 [ADP]) /([ATP] + [ADP] + [AMP] )
Summary card.
- Coupling a favourable one with an unfavourable reaction can drive the latter
- Three ways
-The free energy donor and store in many systems is:
ATP =Continuously being consumed (high turnover)
- NADH and FADH2 are major electron carriers
- Ultimate electron carrier is Oxygen
- NADH and FADH2 electron transfer occurs in the mitochondrial membrane
-Activated Carriers:
Interchanges in metabolism use a small select number of carriers for the process
-Energy from Foodstuffs
-Three stages:
Principal is STAGE 3 => Produces 90% of ATP
-Metabolic Pathway Regulation:
Three principal ways
