Pantothenate is important in many basic physiological functions, and especially as a precursor for Coenzyme A also known as CoA and CoA-SH. CoA is the precursor for the formation of acetylCoA which is an important metabolic intermediary.
Acetyl-CoA is the substrate, intermediary, or product of various energy systems as well as being -
- the actual molecule through which glycolytic pyruvate enters the tricarboxylic acid (TCA) cycle ie necessary for energy generation,
- a signal transducer,
- a precursor of anabolic reactions,
- an allosteric regulator of enzymatic activities,
- a key precursor of lipid synthesis,
- important in the activity of a wide panel of processes (including gene expression) via (de)acetylation reactions,
- a key determinant of protein acetylation,
- the sole donor of the acetyl groups for acetylation.
A range of pharmaceutical agents that focus on various aspects of acetyl-CoA metabolism in health disorders such as diabetes and obesity, are in are in various stages of development. Given the importance of acetylCoA in so many aspects of metabolism, perhaps we need to be aware of the consequences of inadequate acetylCoA and/or it’s precursors.
Acetyl-CoA transporters
Acetyl-CoA is transported by Acetyl-coenzyme A transporter 1 which is also known as ACATN, AT1, AT-1; SPG42; CCHLND.
Aspirin (acetylsalicylic acid) is absorbed from both the stomach and proximal small intestine. Ideal absorption of salicylate occurs in the pH range of -
- stomach - 2.15 - 4.10, unabsorbed at pH 6.5;
- intestinal - 3.5 or 6.5.
Aspirin is transported from blood into kidneys by OAT1/3.
The paper Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells (https://doi.org/10.1038/s41598-019-39489-4) found that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells; the effect was at both gene and protein levels. Proposed mechanism of actions -
- impairment of the carnitine shuttle pathway via impairment carnitine acetyltransferases,
- impairment of the glyoxylate pathway via impairment of peroxisomal citrate synthase.
Both these mechanisms are important in the transfer of acetyl-CoA into the mitochondria.
Clinical Concerns
Should we, as busy clinicians, be concerned about negative impacts on acetylCoA? There is very limited evidence on this subject so I suggest we need to be very cautious and not be influenced by the hype surrounding diabetes and body size; perhaps as a precaution, we should be clarifying carnitine status and effectiveness.
Clinical Questions
Next time you see someone prescribed aspirin will you –
- request clarification of carnitine status?
- monitor triglyceride and cholesterol levels for an impact via acetylCoA?
Conclusions
There is limited evidence in relation to the negative impact of aspirin on acetylCoA function, however what is available is concerning.
Case study
The comments refer to the drug-nutrient, drug-food, and PharmacoNutrition effects only.
Data summary
Medical History with Nutritional Aspect
Biochemistry with Pharmaconutritional Consequences
No recent relevant biochemistry available.
Medications That May Adversely Affect Nutritional Status
Biochemistry
No recent relevant biochemistry available. Advisable to check plasma proteins (albumin, total proteins) as markers of nutritional status. The plasma proteins are the primary transporters for three of the prescribed drugs and hypoproteinaemia may alter their effects.
Pharmaconutrition
Risperidone associated with increased risk of diabetes therefore advisable to monitor on a regular basis.
Chronic use of Coloxyl + senna may promote excessive loss of water and electrolytes, especially potassium, and their regular monitoring recommended.
Dietary levels of caffeine intake in conjunction with Panadol inhibit antinocieception.
Concurrent ingestion of Panadol and iron resulted increased rate of iron absorption and decreased extent of drug absorption; the authors advise drug and iron to be administered at different times from each other.
Bowel management
- regular aperient prescribed,
- oral PRN aperients prescribed: administered 1 x Nov,
- no Nurse Initiated interventions administered.
Staff comments
Staff advise Mrs ABT mostly eats well and agree she could probably manage more.
Observations
Mrs ABT is a pale, rubinesque lady who was sitting in the Day Room watching TV - she responded to some of my questions and told me she eats well.
Pharmaconutrition comments
The side effects of all five of the prescribed medications includes nausea.
The side effects of four of the prescribed medications includes nausea and diarrhoea.
Advisable to review daily food and fluid intake for 3 days and ensure a stable and adequate daily intake of vitamin K – women require a minimum 90 mcg/day.
Chronic pain
Mrs ABT’s diagnoses include chronic pain - nutritional factors that may be useful to consider in pain management include -
- vitamin D - current intervention may not be adequate to attain adequate range and currently prescribed warfarin. Evidence indicates increasingly brittle pain control with decreasing vitamin D levels. Advisable to check vitamin D levels and if low then review current vitamin D management strategy;
- vitamin K - has been found to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury to oligodendrocytes and neurons – vitamin K deficiency therefore results in classic expression of the inflammatory response and consequently pain, and currently prescribed warfarin.
Both liver and kidney uptake of thiamine are inhibited by risperidone and Aricept, therefore there is increased of serum thiamine levels and likely altered within-organ metabolism.
What else would you include?
Please read this as it is important …
The information in this article is provided to support Health Professionals. It is not an exhaustive protocol and Health Professionals are advised that adequate professional supervision is accessed to ensure that Duty of Care obligations with respect to safe administration of medicines is met for each consumer.
Yvonne Coleman has 30+ years of experience in aged care as a dietitian. Her mission is to make information about interactions between medicines and nutrition easy to access for those working in the healthcare sector. She has created a comprehensive resource identifying drug-nutrient and drug-food interactions from a nutrition perspective.
Her areas of competency include food science & nutrition, dietetics and health education. You can find out more about her work on LinkedIn, AusMed, the Enlightened Pharmacist podcast, and The FX Medicine Podcast.
