CPS1
Carbamoyl phosphate synthetase I (CPS1) is a protein located in the mitochondria which is involved in the clearance of ammonia formed during the breakdown of proteins and is encoded for by the CPS1 gene. CPS1 is a key driver of protein and nitrogen metabolism and the clearance of the resulting ammonia. Ammonia enters the mitochondria via glutamine or glutamate 1. CPS1 cleaves this ammonia and adds it to a bicarbonate molecule along with another molecule to form carbamoyl phosphate. Carbamoyl phosphate the leaves the mitochondria and enters the urea cycle for subsequent excretion from the body 2.
See also: Can your body handle a high protein diet? The answer may be genetic
Carbamoyl phosphate synthetase I deficiency is a severe clinical loss of CPS1 activity which results in the accumulation of ammonia in the blood, which results in severe neurological issues 3. Several SNPs have demonstrated an association with this severe clinical disorder, however those affected will have been identified based on symptoms evident at birth.
There is however one SNP which is associated with altered, but not a complete loss of, CPS1 activity C4235A (T1405N) or rs1047891 (sometimes called rs7422339).
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) | Major Amino Acid | Minor Amino Acid |
|---|---|---|---|---|---|
| rs1047891 | c | a | 33 | Thr | Asn |
Risk Description
The ‘A’ allele of C4235A in the CPS1 gene is associated with increased homocysteine levels and therefore cardiovascular risk. Alongside this an increase in total cholesterol and low density lipoprotein (LDL) cholesterol has also been observed potentially further increasing cardiovascular risk 4.
Another study demonstrated an alteration in the response of the circulatory system to nitric oxide (NO). NO is a vasodilator which is used to alter the size of blood vessels and thus modulate blood pressure. Those carrying the risk ‘A’ allele displayed a reduced responsiveness to NO suggesting they may be at risk of increased risk of high blood pressure, an effect which was increased in those carrying two ‘A’ alleles 5.
The authors initially hypothesized that this effect was due to reduced enzyme activity. However, this effect was not confirmed upon investigation with the authors therefore suggesting that CPS1 may be acting directly on the circulatory system, independently of NO activity. As such this effect requires further study.
Indirect Nutrients:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Nattō | Nattokinase |
Nattokinase is an enzyme which is extracted and purified from a Japanese food called nattō, derived from fermented soybeans. Nattokinase is secreted by the bacteria involved in the fermentation process and has a very strong ability to break down fibrin blood clots 6. A beneficial effect on blood pressure 7, and general cardiovascular health has been described 8. Therefore, supplementation may benefit those carrying the risk ‘A’ allele of C4235A, who may be at increased risk of cardiovascular risk and increased blood pressure. |
| Bergamot Oil | Melitidin and Brutieridin |
Bergamot orange is a sour citrus fruit similar in size to an orange which was originally grown in areas bordering the Mediterranean. Bergamot oranges were frequently processed into oil for a variety of cosmetic reasons. However, more recently positive health effects have been described for two flavone molecules found only in bergamot oranges; melitidin and brutieridin. Both of these flavones exhibit strong statin (blood pressure lowering) 9 like properties, and also lower lipids present in the blood 10, without a lot of the side affects associated with statin use. As such supplementation may benefit those carrying the risk ‘A’ allele of C4235A, which is associated with an increased cardiovascular risk and elevated blood pressure as well as an altered blood lipid profile. |
| Vitamin B6 | Pyridoxal phosphate |
Cystathionine β synthase (CBS) and cystathionine γ ligase are key enzymes involved in the conversion of the harmful homocysteine into the less harmful cysteine. Both enzymes use vitamin B6 as a cofactor, and in the absence of vitamin B6 the activity of both enzymes is reduced. Therefore, supplementation with vitamin B6 may aid in the conversion of homocysteine into cysteine 11–12. Therefore, reducing the cardiovascular risk for those carrying the ‘A’ allele of C4235A. |
| Vitamin B12 | Methylcobalamin |
Vitamin B12 is a co-factor for methionine synthase (MS), which converts the harmful homocysteine into the less harmful methionine. Vitamin B12 binds with MS and allows it to function optimally, therefore when present in low levels MS activity is reduced. This activity accounts for approximately half of the processing of homocysteine into methionine. Supplementation with B12 will aid the activity of MS which may help reduce homocysteine levels 13–14. Supplementation may therefore prove beneficial to those with the risk ‘A’ allele of C4235A who display elevated homocysteine levels. |
Discuss this information with your doctor before taking any course of action.
Citations:
- https://ghr.nlm.nih.gov/gene/CPS1
- https://www.ncbi.nlm.nih.gov/pubmed/11212301
- https://omim.org/entry/237300
- https://www.ncbi.nlm.nih.gov/pubmed/20154341
- https://www.ncbi.nlm.nih.gov/pubmed/14718356
- https://www.ncbi.nlm.nih.gov/pubmed/8280151
- https://www.ncbi.nlm.nih.gov/pubmed/18971533
- https://www.ncbi.nlm.nih.gov/pubmed/28264497
- https://www.ncbi.nlm.nih.gov/pubmed/19572741
- https://www.ncbi.nlm.nih.gov/pubmed/21056640
- http://pubs.acs.org/doi/abs/10.1021/bi00759a011
- https://www.ncbi.nlm.nih.gov/pubmed/9884399
- https://www.ncbi.nlm.nih.gov/pubmed/2407589
- https://www.ncbi.nlm.nih.gov/pubmed/9884399