Anabolism-the creation of order by the synthesis of complex molecules from simpler ones; it requires the input of energy
Turnover-the continual degradation and resynthesis of cellular constituents
The rate of biosynthesis is approximately balanced by that of catabolism, due to careful regulation of metabolic processes
Principles Governing Biosynthesis
Biosynthetic metabolism follows a few general principles:
The synthesis of large complex molecules (macromolecules) from a limited number of simple structural units (monomers) saves much genetic storage capacity, biosynthetic raw material, and energy
The use of many of the same enzymes for both catabolism and anabolism saves additional materials and energy
Many biosynthetic pathways are reversals of catabolic pathways; many steps of the pathway are catalyzed by enzymes that participate in both catabolic and anabolic activities; however, some steps are catalyzed by two different enzymes: one that functions in the catabolic direction and second that functions in the biosynthetic direction; this permits independent regulation of catabolism and anabolism
Coupling some biosynthetic reactions with the breakdown of ATP (or other nucleoside triphosphates) drives the anabolic pathways irreversibly in the direction of biosynthesis
In eucaryotic cells, anabolic and catabolic reactions involving the same constituents are frequently located in separate compartments for simultaneous but independent operation
Catabolic and anabolic pathways use different cofactors: catabolic oxidations produce NADH, which is a substrate for electron transport, while NADPH acts as a reductant for anabolic pathways
Once macromolecules have been made from simpler precursors, cell structures (e.g., ribosomes) form spontaneously from the macromolecules by a process known as self-assembly
The Photosynthetic Fixation of Carbon Dioxide
Three different processes for converting carbon dioxide into organic carbon are known
Calvin cycle (reductive pentose phosphate cycle)-observed in photosynthetic eucaryotes and many photosynthetic bacteria
Reductive TCA cycle-used by some archaea and bacteria
Acetyl-CoA pathway-used by methanogens, sulfate reducers, and acetogens
Calvin cycle
Consists of three phases
The carboxylation phase-the enzyme ribulose 1,5-bisphosphate carboxylase catalyzes the addition of carbon dioxide to ribulose 1,5-bisphosphate, forming two molecules of 3-phosphoglycerate
The reduction phase-3-phosphoglycerate is reduced to glyceraldehyde 3-phosphate
The regeneration phase-a series of reactions is used to regenerate ribulose 1,5-bisphosphate and to produce carbohydrates such as fructose and glucose; this phase is similar to the pentose phosphate pathway and involves transketolase and transaldolase reactions
Each carbon dioxide takes three ATP molecules and two NADPH molecules, thus the formation of a single glucose molecule requires six turns through the cycle with an expenditure of 18 ATP molecules and 12 NADPH molecules; sugars formed in the Calvin cycle can then be used to synthesize other essential molecules
Synthesis of Sugars and Polysaccharides
Heterotrophs synthesize glucose from noncarbohydrate precursors in a process called gluconeogenesis; the gluconeogenic pathway is a functional reversal of glycolysis-it shares seven enzymes with the glycolytic pathway, reversing their catabolic direction, and uses several distinct enzymes or multi-enzyme systems to catalyze steps that cannot be directly reversed
Once glucose and fructose are synthesized by gluconeogenesis, other sugars are manufactured; several of these other sugars are synthesized while attached to a nucleoside diphosphate
Polysaccharide production also requires the use of nucleoside diphosphate sugars as precursors
The Assimilation of Inorganic Phosphorus, Sulfur, and Nitrogen
Phosphorus assimilation
Inorganic phosphates are incorporated through the formation of ATP by photophosphorylation, oxidative phosphorylation, and substrate-level phosphorylation
Organic phosphates obtained from the surroundings are hydrolyzed to release inorganic phosphates by enzymes called phosphatases
Sulfur assimilation
Organic sulfur in the form of cysteine and methionine can be obtained from external sources
Assimilatory sulfate reduction is used to reduce inorganic sulfate before it is incorporated into cysteine
Nitrogen assimilation
Ammonia incorporation
Many microorganisms use reductive amination to make alanine and glutamate, which are then used as sources of amino groups; the amino groups are transferred from alanine or glutamate to other carbon skeletons by transamination reactions
Other microorganisms use the enzymes glutamine synthetase and glutamate synthase to synthesize glutamate, which then acts as an amino group donor in transaminase reactions
Assimilatory nitrate reduction-involves the reduction of nitrate to nitrite, then to hydroxylamine, and finally to ammonia, which can then be incorporated by the routes described above
Nitrogen fixation-the reduction of atmospheric nitrogen to ammonia; this is catalyzed by the enzyme nitrogenase, which is found in only a few species of bacteria; nitrogen fixation requires an expenditure of 16 ATP molecules; the ammonia produced can be incorporated into organic molecules by the processes described above
The Synthesis of Amino Acids
Involves attachment of an amino group to a carbon skeleton
Carbon skeletons are derived from acetyl-CoA and from intermediates of the TCA cycle, glycolysis, and the pentose phosphate pathway
Anaplerotic Reactions
Biosynthetic functions of the TCA cycle are so important that many of its intermediates must be synthesized even when the TCA cycle is not functioning to catabolize pyruvate or to provide NADH for electron transport
Anaplerotic reactions replenish TCA cycle intermediates so that biosynthesis can occur; two major types of anaplerotic reactions have been observed
Glyoxylate cycle-used by microorganisms that can grow on acetate as a sole carbon source; is a modified TCA cycle
The Synthesis of Purines, Pyrimidines, and Nucleotides
These molecules are critical for all cells because they are used in the synthesis of ATP, several cofactors, RNA, and DNA
Purine biosynthesis-very complex pathway in which seven different molecules (including folic acid) contribute parts to the final purine skeleton; the first purine product is the nucleotide inosinic acid, from which all other purine nucleotides can be made
Pyrimidine biosynthesis-aspartic acid and carbamoyl phosphate form the initial pyrimidine product (orotic acid), which can then be converted to pyrimidine nucleotides
Lipid Synthesis
Fatty acid synthesis is catalyzed by fatty acid synthetase using the substrates acetyl-CoA and malonyl-CoA, the reductant NADPH, and a small protein called acyl carrier protein, which carries the growing fatty acid chain; the fatty acid is lengthened by adding two carbons at a time to its carboxyl end
Triacylglycerols are formed from the reduction of dihydroxyacetone phosphate (a glycolytic pathway intermediate) to glycerol 3-phosphate, which then undergoes esterification with two fatty acids to form phosphatidic acid; this can then be used to produce triacylglycerol
Phospholipids are also produced from phosphatidic acid using a cytidine diphosphate (CDP) carrier
Peptidoglycan Synthesis
A multistep process that involves two carriers: uridine diphosphate and bactoprenol; during the process a peptidoglycan repeat unit is formed and is attached to the growing peptidoglycan chain after being transported across the cytoplasmic membrane; crosslinks are then formed by transpeptidation
Peptidoglycan synthesis is very vulnerable to disruption by antimicrobial agents, including antibiotics such as penicillin; inhibition of any step in the process weakens the cell wall and can cause lysis
Patterns of Cell Wall Formation
Autolysins carry out limited digestion of peptidoglycan, and provide acceptor ends for the addition of new peptidoglycan units
Two general patterns of cell wall synthetic activity have been observed
Many gram-positive cocci have only one or a few growth zones, usually at the site of septum formation
Rod-shaped bacteria usually have growth sites scattered along the cylindrical portion of the cell as well as at the site of septum formation
