Medical Biochemistry - Amino Acids and Metabolites

Amino acids serve as the monomeric units of proteins, act as precursors for neurotransmitters and hormones, and provide key intermediates for energy and one-carbon metabolism. At physiological pH they exist as zwitterions and can be classified as essential (must be obtained from the diet) or non-essential (synthesised endogenously), and as glucogenic or ketogenic depending on their catabolic fates. Dietary proteins are hydrolysed to amino acids in the gut, absorbed via Na⁺–amino acid co-transporters and distributed to the liver and peripheral tissues. Non-essential amino acids are synthesised mainly by reversible transamination reactions that link α-keto acids to the amino pool via pyridoxal phosphate–dependent aminotransferases. Excess nitrogen is shuttled to the liver largely as glutamine or alanine, where it is released to feed the urea cycle, eliminating two nitrogen atoms per molecule of urea. The carbon skeletons of amino acids enter central pathways such as glycolysis, the tricarboxylic acid cycle or ketogenesis. Flux through serine and one-carbon pathways supports nucleotide, glutathione and methyl donor synthesis, while proline metabolism modulates redox balance, collagen deposition and metastatic potential. Dysregulation of amino acid homeostasis underlies inherited disorders of the urea cycle and amino acid biosynthesis, contributes to hepatic encephalopathy and cancer metabolic reprogramming, and offers therapeutic targets ranging from dietary modification to enzyme inhibition.

Research from Nature Portfolio

Hypoxia–responsive phosphorylation of pyrroline-5-carboxylate reductase 1 by nuclear IGF1R has been shown to enhance enzyme recruitment to transcriptional regulators, sustaining proline synthesis and colorectal tumour growth under low-oxygen conditions. Inhibition of this modification reduces proline production, amplifies oxidative stress and impairs tumour expansion in preclinical models. Complementary studies have revealed that mitochondrial NADP+, generated by NADK2, is essential for proline biosynthesis; loss of mitochondrial NADP+ renders cells auxotrophic for proline and sensitises tumours to oxidative damage. Foundational structural work on cationic amino acid transporters has elucidated arginine recognition by SLC7 family members, providing templates for inhibitor design against tumour-associated overexpression in diverse malignancies.

Medical Biochemistry - Amino Acids and Metabolites publication trend

The graph below shows the total number of articles in medical biochemistry - amino acids and metabolites across all publications each year (not limited to Nature Index journals).

Technical terms

Zwitterion: A molecule carrying both positive and negative charges, as amino acids do at physiological pH.

Aminotransferase: Enzymes that catalyse the reversible transfer of amino groups between amino acids and α-keto acids, requiring pyridoxal phosphate.

Urea cycle: A hepatic pathway converting ammonia and aspartate into urea, enabling nitrogen disposal.

Pyrroline-5-carboxylate reductase (PYCR1): Mitochondrial enzyme reducing P5C to proline, critical for proline biosynthesis and redox homeostasis.

Phosphoglycerate dehydrogenase (PHGDH): Rate-limiting enzyme of de novo serine synthesis, linking glycolysis to one-carbon metabolism.

Phosphoserine aminotransferase (PSAT1): Converts 3-phosphohydroxypyruvate to phosphoserine, a key step in serine biosynthesis and signalling cross-talk with p53.

References

1. Amino acid homeostasis and signalling in mammalian cells and organisms. Biochemical Journal (2017).
2. IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia. Nature Communications (2023).
3. Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. Nature Metabolism (2021).
4. Structural basis for amino acid transport by the CAT family of SLC7 transporters. Nature Communications (2018).
5. Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant. Signal Transduction and Targeted Therapy (2023).
6. Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate. Cell Research (2023).
7. Proline metabolism shapes the tumor microenvironment: from collagen deposition to immune evasion. Current Opinion in Biotechnology (2023).