Serine Metabolism in Health and Disease and as a Conditionally Essential Amino Acid
Abstract
:1. Introduction
2. Sources of Serine
2.1. Dietary Sources
2.2. Degradation of Endogenous Proteins
2.3. Synthesis from 3-PG and Glycine
2.3.1. Synthesis from 3-PG
2.3.2. Synthesis from Glycine
2.3.3. Role of the Kidneys in Serine Synthesis
3. Serine Degradation
4. Transporters
- System A (alanine preferring)—a sodium-dependent transporter for small neutral amino acids. It is found in most cell types of the body and includes transporters SNAT1 (SLC38A1), SNAT2 (SLC38A2), and SNAT4 (SLC38A4). Transporter recruitment from vesicles under the plasma membrane to the cell surface is sensitive to amino acid levels and hormones (notably to insulin and glucagon). The system plays a role in tissue amino acid uptake after food intake and in hepatic amino acid uptake to be used for gluconeogenesis during starvation [22,23,24].
- System ASC (alanine, serine, and cysteine preferring)— a sodium-dependent transporter, which includes transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). It is supposed that ASCT1 is the main transporter for serine in the brain, where it plays a key role in transporting serine from astrocytes and serine uptake by neurons [25]. ASCT1 mutations cause a disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum [26].
- System asc—a heterodimeric (SLC7A10/SLC3A2) sodium-independent amino acid exchanger. The system includes transporter Asc-1, which is expressed in the brain and has a high affinity for both L- and D-serine [27].
5. Physiological Functions
5.1. L-Serine and Proteins
5.2. L-Serine and Folate and Methionine Cycles
5.3. L-Serine and Transsulfuration Pathway
5.4. L-Serine and Sphingolipids (SL)
5.5. L-Serine and Phosphatidylserine (PS)
5.6. Serine and Neurotransmission (D-Serine)
5.6.1. L-Serine
5.6.2. Glycine
5.6.3. D-Serine
6. Serine and Disease
6.1. Primary Disorders of L-Serine Synthesis
6.2. Hereditary Sensory Neuropathy Type 1
6.3. Disorders of the Nervous System
- L-serine supplementation has been investigated in the therapy of central nervous system injury, such as that due to cerebral ischemia, stroke, and trauma [40].
- L-serine has shown therapeutic potential in amyotrophic lateral sclerosis [8].
- Clinical trials indicate that PS may prevent and treat depression and age-related cognitive disorders like Alzheimer’s disease [39].
6.4. Serine and Diabetes Mellitus
6.5. Serine and Kidney Diseases
D-Serine
6.6. Serine and Cancer
6.7. Serine and Hyperhomocysteinemia
7. L-Serine as a Conditionally Essential Amino Acid
8. Conclusions
- There are primary disorders of L-serine synthesis resulting in L-serine deficiency.
- Humans cannot synthesize L-serine in sufficient quantities in diabetes and chronic kidney diseases.
- L-serine deficiency is associated with severe neurological abnormalities.
- It was proved that L-serine supplementation is effective in therapy of primary disorders of serine metabolism and diabetic neuropathy.
Funding
Conflicts of Interest
References
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Holeček, M. Serine Metabolism in Health and Disease and as a Conditionally Essential Amino Acid. Nutrients 2022, 14, 1987. https://doi.org/10.3390/nu14091987
Holeček M. Serine Metabolism in Health and Disease and as a Conditionally Essential Amino Acid. Nutrients. 2022; 14(9):1987. https://doi.org/10.3390/nu14091987
Chicago/Turabian StyleHoleček, Milan. 2022. "Serine Metabolism in Health and Disease and as a Conditionally Essential Amino Acid" Nutrients 14, no. 9: 1987. https://doi.org/10.3390/nu14091987