General principles of biosynthesis
Constructive metabolism is fundamentally based on polymerization. Large polymers—proteins, lipids, and nucleic acids—are assembled from small building blocks (amino acids, nucleotides, sugar phosphates, organic acids). These processes occur with obligatory energy absorption.
Bacteria source materials for biosynthesis directly from energy metabolism pathways. Depending on their degree of enzymatic autonomy, microorganisms are divided into two polar groups:
- Prototrophs are capable of synthesizing absolutely all cellular components from scratch, utilizing only a single carbon and energy source.
- Auxotrophs have lost the ability to produce certain enzymes or substances due to various mutations. They require preformed growth factors from the environment (vitamins, amino acids, nitrogenous bases), without which their reproduction halts.
Amino acid biosynthesis and proper protein folding
Most bacteria can synthesize all 20 proteinogenic amino acids. Their carbon skeletons are supplied by three fundamental metabolic pathways: glycolysis (fructose diphosphate pathway), the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. Key precursor molecules include pyruvate, $\alpha$-ketoglutarate, oxaloacetate, fumarate, erythrose-4-phosphate, and ribose-5-phosphate.
Nitrogen is incorporated into upcoming amino acids via amination and transamination reactions. Inorganic sources (nitrates, nitrites, molecular nitrogen $N_2$) cannot be utilized directly—they are first reduced to ammonia ($NH_3$).
Once a protein is synthesized on the ribosome, it is merely a linear strand. To become functional, it must acquire the correct tertiary structure. Special molecules called chaperones are responsible for this process (folding). They perform three critical tasks:
- Ensuring correct folding of protein chains.
- Providing a protective function by preventing protein destruction (e.g., protecting the DNA polymerase enzyme). Their numbers increase sharply during metabolic disruptions, heat shock, or exposure to toxins.
- Participating in the translocation (transport) of protein molecules across cell membranes.
Formation of nucleotides, lipids, and carbohydrates
Nucleotide biosynthesis Nucleotides serve not only as monomers for DNA and RNA synthesis. They are components of many coenzymes and help activate and transport substrates (sugars, lipids, amino acids) during polymerization. Ribose-5-phosphate (the pentose moiety) for their assembly is supplied by the pentose phosphate pathway. The pyrimidine carbon skeleton is built from aspartate (derived from the TCA cycle), while the nitrogen for the bases is supplied by the amino acids aspartate and glutamine.
Lipid biosynthesis Fatty acid synthesis relies on a key intermediate—acetyl-coenzyme A (acetyl-CoA). To produce phospholipids, bacteria require glycerol-3-phosphate, which is formed by the reduction of dihydroxyacetone phosphate (a glycolysis product). At the final stage, glycerol-3-phosphate combines with fatty acid residues to form mature membrane lipids.
Carbohydrate biosynthesis Cellular carbohydrate synthesis proceeds via gluconeogenesis—the cell assembles glucose from pyruvate through reversible reactions of its breakdown. Since certain catabolic reactions are strictly irreversible, bacteria must employ alternative metabolic pathways (such as the glyoxylate cycle) to bypass these barriers.
Briefly: answers to topical questions
Which amino acids supply nitrogen for the biosynthesis of nucleotide nitrogenous bases?
Nitrogen for the biosynthesis of nucleotide nitrogenous bases is supplied by the amino acids aspartate and glutamine.
- Aspartate serves as the source of nitrogen atom N1 in the purine ring, as well as the carbon skeleton of pyrimidines.
- Glutamine acts as the donor of nitrogen atoms N3 and N9 during de novo purine synthesis, and also supplies the amino group for GMP formation.
Which substances act as growth factors for auxotrophic bacteria?
Organic substances that auxotrophic bacteria have lost the ability to synthesize independently act as growth factors. These include:
- Amino acids—necessary for protein biosynthesis.
- Vitamins—required for normal metabolism.
- Nitrogenous bases (purines and pyrimidines)—used to build nucleic acids.
For certain species (e.g., of the genus Haemophilus), specific growth factors include factor X (protoporphyrin IX or hemin) and factor V (nicotinamide adenine dinucleotide, NAD).
Which coenzymes are required for transamination reactions during amino acid biosynthesis?
Transamination reactions require the coenzyme pyridoxal phosphate (pyridoxal-5-phosphate).
Pyridoxal phosphate is a derivative of vitamin B6. It serves as a coenzyme for aminotransferases (transaminases), which catalyze the transfer of an amino group from an amino acid to $\alpha$-ketoglutarate, yielding an $\alpha$-keto acid and glutamate.
All amino acids undergo transamination except lysine, threonine, and proline.
To easily remember how bacteria incorporate inorganic nitrogen into macromolecules, remember the three "A" rule: Nitrogen is incorporated via Amination strictly after reduction to Ammonia.
Class and exam questions
What is the main difference between auxotrophs and prototrophs?
Prototrophs fully synthesize all cellular components from a single carbon source. Auxotrophs, conversely, are unable to synthesize a number of substances due to mutations, and thus require the addition of preformed growth factors to the culture medium.
Where do bacteria get molecular "skeletons" for amino acids?
Carbon skeletons are borrowed from intermediates of three energy metabolism pathways: glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle.
Why are chaperones needed under normal conditions and under stress?
They ensure correct folding (into the tertiary structure) of synthesized proteins and their transport across membranes. Under stress (heat shock, toxins), their numbers spike sharply to protect proteins from denaturation.
How do bacteria bypass irreversible reactions during glucose synthesis?
For gluconeogenesis (glucose synthesis from pyruvate), bacteria utilize alternative bypass metabolic pathways, a prime example being the glyoxylate cycle.
What else to study on this topic
- The fructose diphosphate pathway (glycolysis) as a supplier of precursors
- The role of the pentose phosphate pathway in microbial metabolism
- The tricarboxylic acid cycle in prokaryotes
- The glyoxylate cycle and bypassing irreversible catabolic reactions
- Mechanisms of molecular nitrogen reduction to ammonia
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