Metabolism

Abstract

Metabolism consists of a series of reactions that occur within cells of living organisms to sustain life. The process of metabolism involves many interconnected cellular pathways to ultimately provide cells with the energy required to carry out their function. The importance and the evolutionary advantage of these pathways can be seen as many remain unchanged by animals, plants, fungi, and bacteria. In eukaryotes, the metabolic pathways occur within the cytosol and mitochondria of cells with the utilisation of glucose or fatty acids providing the majority of cellular energy in animals. Metabolism is organised into distinct metabolic pathways to either maximise the capture of energy or minimise its use. Metabolism can be split into a series of chemical reactions that comprise both the synthesis and degradation of complex macromolecules known as anabolism or catabolism, respectively. The basic principles of energy consumption and production are discussed, alongside the biochemical pathways that make up fundamental metabolic processes for life.

Keywords: biochemistry; glycolysis; metabolism.

Figure 1. Coupling of anabolic and catabolic pathways

Anabolism utilises energy to make macromolecules and biomolecular polymers. Catabolism releases energy when these are broken down into simpler molecules.

Figure 2. Reaching equilibrium

If you increase the concentration of A and B, this pushes the reaction to make more C and D. If you do the opposite and add more C and D, then the reverse reaction occurs. The aim is to bring the reaction back to equilibrium.

Figure 3. The effect of changes in ΔG on the reaction A+B and C+D

Figure 4. The role of nitrogen in generating macromolecules in chemoautotrophs – AOB, NOB, NH₄⁺, NO₂⁻, and NO₃⁻

Figure 5. Basic pathway of photosynthesis and biosynthesis in green plants

Figure 6. Summary of metabolic pathways active during starvation

During starvation, there is an increase in fatty acid utilisation in the muscle (not shown here for simplicity) and a breakdown of proteins into amino acids. Intermediates (in black), tissues (in green), and pathways (in red).

Figure 7. The two key pathways to recycle lactate or alanine from muscle and regenerate glucose in the liver

Intermediates (in black), tissues (in green), and pathways (in red).

Figure 8. The metabolic crossroad and fate of G6P

G6P links four key metabolic processes; glycolysis, gluconeogenesis, glycogenesis/glycogenolysis, and the PPP.

Figure 9. The pathway is split into an initial ‘investment’ phase, where ATP is used and then the ‘payout’ phase, where ATP is regenerated

Intermediates (in black), by-products (in green), and enzymes (in red).

Figure 10. PPP is split into the oxidative and non-oxidative phases

The oxidative phase represents the conversion of G6P into ribulose-5-phosphtase which generates NADPH molecules. The non-oxidative phase shows the generation of ribose-5-phosphate and also glycolysis pathway intermediates. Intermediates (in black), by-products (in green), and enzymes (in red).

Figure 11. The chemical structural differences amongst saturated, monosaturated, and polyunsaturated fatty acids

Saturated fatty acids hold no double bond within their structure meaning the carbon atoms are fully ‘saturated’ with hydrogens. Monounsaturated fats have one carbon–carbon double bond in their structure and polyunsaturated hold two or more.

Figure 12. β-oxidation process of fatty acids including the enzymes involved

The process results in the formation of acetyl CoA and acyl CoA molecules from the oxidation, hydration, and cleavage of fatty acyl CoA. Intermediates (in black), by-products (in green), enzymes (in red), and black boxes summarise the steps.

Figure 13. FAS domains and their respective catalytic sites

Figure 14. The categorisation of amino acids into their essential, conditional and non-essential groups in humans

Conditional amino acids are not usually essential amino acids, only in times of illness and stress. Essential amino acids are not produced naturally by the body and must come from dietary intake whereas non-essential amino acids are produced by our body.

Figure 15. The TCA cycle with all intermediates (in black), by-products (in green), and enzymes (in red)

The TCA cycle proceeds after the formation of acetyl CoA from either pyruvate during aerobic respiration following glycolysis or β-oxidation. The TCA cycle forms carbon dioxide, NADH, GTP, and FADH₂ molecules.

Figure 16. The anaplerotic and cataplerotic reactions within the TCA cycle

The major reactions are illustrated here including the entry of amino acids, formation and breakdown of oxaloacetate and the link to gluconeogenesis.

Figure 17. The glyoxylate shunt (green) coexisting amongst the TCA cycle (black)

The glyoxylate shunt converts fatty acids into carbohydrates by bypassing decarboxylation steps of the TCA cycle.

Figure 18. Basic structure of the mitochondrion and chloroplast, showing the membrane structures

Figure 19. Oxidative phosphorylation – ETC and ATP synthase

Drawn from PDB and OPM codes: 5XTD (Complex I), 1ZOY (Complex II), 1L0L (Complex III), 2DYR (Complex IV) and 6J5I (ATP synthase).

Figure 20. As electrons (e-) are passed along the chain, they reduce the next carrier and decrease their energy levels, until they reach the final electron acceptor – oxygen

Figure 21. The urea cycle intermediates and by-products

Ornithine is imported into the mitochondria, where it combines with carbomoyl phosphate to generate citrulline. Citriuline is exported to the cytosol, where the cycle continues, until the release of urea and the regeneration of ornithine.

Figure 22. The hallmarks of cancer development put forward by Hanahan and Weinberg in 2011

Deregulated cellular energetics is included in these hallmarks as a driver of cancer progression.

Figure 23. The Warburg effect

A cell with no oxygen supply generates lactate as it undergoes glycolysis anaerobically. In aerobic conditions, with oxygen, a cell proceeds with oxidative phosphorylation yielding a higher number of ATP molecules. However, in a cancer tumour microenvironment, the ability to carry out oxidative phosphorylation is disrupted, despite oxygen presence. Instead, lactate is formed, and a cell is suggested to undergo aerobic glycolysis.

Figure 24. Increased glucose and glutamine uptake and utilisation drive the increased synthesis of nucleotide, protein, and lipid synthesis in cancer cells

The up-regulation of glycolysis increases cellular lactate concentrations.