Introduction:

Metabolism is the sum total of all of the chemical reactions taking place in a living organism. It can be divided into catabolism, the degradation of complex molecules into simpler ones and anabolism, the synthesis of more complex molecules from simpler ones.

Metabolic strategies:

a. ATP is the universal currency of cellular energy, it drives reactions in metabolically favorable, but thermodynamically unfavorable, directions by a factor of 10⁸.

b. ATP is generated from oxidation reactions; predominantly in glycolysis and the TCA cycle, where glucose, amino acids, and fatty acids can be converted into carbon dioxide and water.

c. As noted previously, NADPH is generally the electron donor in reductive, biosynthetic reactions, NADH is utilized predominantly in redox reactions and energy production.

d. The large numbers of diverse biological molecules found in living systems are synthesized from a relatively small number of simple precursor molecules. For example, the protophorphryin IX ring of heme is synthesized from succinate and glycine!

e. Biosynthetic and biodegradative pathways are almost always separated. This facilitates the control of metabolic rates via regulation of enzyme activity, rather than by mass action. It also makes it easier to prevent "futile cycles", which have the net result of hydrolyzing ATP for no metabolic gain other than heat production.

Sites for regulation of metabolism:

There are two rules of thumb for thinking about regulation of metabolic sequences.

rule 1: In metabolic pathways, enzymes catalyzing essentially irreversible reactions are good candidates for regulation.

rule 2: In metabolic pathways that branch, control is often exerted after the branch point. This first reaction after the branch point constitutes the first committed step to that branch of the pathway.

A Review of types and levels of regulation:

a. allosteric interactions - an example is the regulation of aspartate transcarbamoylase

b. covalent modification - examples are glycogen synthetase and glutamine synthetase

c. enzyme levels - examples are the lactose operon, zymogen activation, and proteolytic degradation

d. compartmentation - examples are the mitochondrion and its shuttle reactions

e. organ specialization - an example is hormonal regulation

Levels of study of metabolism:

a. whole organism (from rats, to yeast, to bacteria); often studied in physiology
b. isolated (perfused) organs; part of physiology
c. whole cells (tissue culture); part of physiology, cell biology, and biochemistry
d. cell-free extracts and organelle preparations; part of cell biology and biochemistry
e. purified components, such as proteins and DNA; biochemistry and molecular biology

Tools for the study of metabolism:

These are a number of ways of identifying and studying pathways and processes.

a. metabolic inhibitors, such as cyanide, cyclohexamide, fluoride, and tetrodotoxin
b. mutations (genetic inhibition)
c. use of radioisotopes; examples are the study of photosynthesis, glycolysis, TCA cycle, DNA replication, mRNA synthesis, protein synthesis, genetic code, the fate of drugs, sequencing of DNA.

Radioisotopic techniques include the use of radioautography, pulse-chase experiments, ligand binding, and analysis of reactant - product relationships.