Introduction to Metabolism Flashcards
Catabolism
Catabolism, which is degradative in nature, has the primary function of supplying the energy for work and anabolic processes:
- degradative (complex → simpler)
- oxidative
- energy releasing (exergonic)
- ATP generation
Anabolism
Anabolism is the sum of the pathways that are involved in synthesis and growth. These processes, and all work functions, require the input of energy:
- synthetic (simple → complex)
- reductive
- energy consuming (endergonic)
- ATP utilization
Thermodynamic Coupling
The endergonic reactions involved in anabolism and other energy requiring processes are linked to the exergonic reactions of catabolism by thermodynamic coupling.
Thermodynamic coupling of an energyrequiring
or endergonic reaction (+ ∆G) with an energy-producing or exergonic reaction (- ∆G) can occur provided the net ∆G is negative and there exists an intermediate common to both reactions. In an enzyme catalyzed reaction the
common intermediate may not be free and may exist only on the enzyme
What metabolic processes are reflected in basal metabolic rates?
The basal metabolic rate is due to involuntary muscle
work and cell turnover, but the major requirement for the basal metabolism is maintaining osmotic gradients and thermogenesis.
Are the reactions A → B and B → C coupled? How can the reactions A → B and C → D be coupled?
In the first reaction, A → B and B → C, B is a common intermediate. In the second case the reactions could be coupled if there existed an intermediate such as [AC] that exists only on the enzyme (E-[AC]). We will see examples when we look at the TCA cycle
Standard Reduction Potentials (E°)
A negative reduction potential indicates a weaker affinity for electrons than a proton has, and a positive reduction potential indicates a stronger affinity.
In a cell, reduction potentials are dependent on the concentrations of the oxidant/oxidizing agent (starts out oxidized, if gains electrons gets reduced) and reductant/reducing agent (starts out reduced, if donates electrons gets oxidized),
The two nicotinamide nucleotides, NAD and NADP, have approximately the same standard reduction potentials, but in the cell (non-standard conditions) NADP has a much more negative reduction potential than NAD. Which of the two nucleotides exists in the cell primarily in its reduced form?
The standard reduction potential (E°′) is a constant, and so never varies (analogous to the standard free energy, ∆G°′). The E°′ for both NAD and NADP is approximately the same (and is slightly negative). However, under non-standard conditions, i.e. in a cell, the reduction potential
is a function of the ratio of oxidant to reductant. Given that NADP has a more negative reduction potential than NAD under these conditions, the ratio of oxidant to reductant is smaller for NADP than for NAD. The primary form of the NADP+/NADPH redox pair is the reduced form (NADPH), and the redox pair functions primarily as an electron donor: NADPH gets oxidized to NADP+ as something else gets reduced. The more negative the reduction potential, the greater the tendency for a redox
pair’s reductant to become oxidized.
For NAD (generic), the ratio of oxidant to reductant is high, the primary form is NAD+ and the redox pair serves primarily as an electron acceptor: NAD+ gets reduced to NADH. A higher ratio of oxidant to reductant results in the log term of the equation being more positive (less negative). The more positive the reduction potential, the greater the tendency of the redox pair’s oxidant to become reduced.
High-energy bonds
The term, “high-energy bond”, is used by biochemists to describe a bond which has a large negative standard Gibb’s free energy (∆G°′) of hydrolysis. The ∆G°′ of hydrolysis of ATP to ADP + Pi is -7.3 kcal/mole.
What are 5 examples of high-energy bonds:
Phosphoenolpyruvate (PEP), Creatine Phosphate (CP), Acetyl CoA (thioester), ATP, and Pyrophosphate (PPi)
In reactions with large positive ∆G, where the hydrolysis of more than one phosphoanhydride bond of ATP is required, what is the role of the enzymes pyrophosphatase and adenylate kinase?
The reaction would involve the conversion of ATP → AMP + PPi. This is then coupled to the hydrolysis of PPi by a pyrophosphatase. The AMP reacts with ATP via adenylate kinase, and the 2 ADP produced get phosphorylated to ATP.
Cosubstrate metabolic pool using adenine as an example
The adenine nucleotides (ATP, ADP, AMP) function as coenzyme-cosubstrates and illustrate the behavior of a cosubstrate metabolic pool.
adenylate kinase
AMP + ATP ↔ 2 ADP
Clearly, the AMP level in the cell is the most sensitive parameter of change in the adenine nucleotide pool and, in the cytosol of the cell, usually initiates the responses to decreased ATP levels. (AMP levels INCREASE if energy levels DECREASE).
Would the adenylate nucleotide pool of the mitochondria, where adenylate kinase is absent, show a similar behavior?
No. The enzymes and reactions of the mitochondria are totally different from those of the cytosol with limited exchange of the adenine nucleotides.
Would you expect AMP to be important in the control of glycolysis, the pathway that initiates the production of ATP from the oxidation of glucose? In β-oxidation, the
pathway that produces ATP from the oxidation of fatty acids?
Under normal conditions in the cell AMP is the most sensitive parameter of changes in the adenine nucleotide pool and is, therefore, the major signal for the increase in
catabolism to replenish the ATP.
Glycolysis is one such catabolic pathway, and it is activated allosterically by AMP. As we will see later, fatty acid oxidation is another major source of ATP and so also is stimulated by AMP; however, the mechanism is more complex
In case of vascular blockage as in a stroke or coronary infarct, what would be the response of the adenylate nucleotide pool in the cytosol?
The restriction of oxygen availability decreases the ability to synthesize ATP from ADP and Pi by oxidative phosphorylation; thus, ATP levels fall and AMP levels rise.
