The Birth of MS/MS Screening
Donald Chace |
Advances in metabolomics drive a parallel surge in metabolite discovery – and inspire new platforms able to measure increasing numbers of compounds in blood, plasma or urine. Our ability to perform such analyses at the microsample scale – a single drop of blood dried on filter paper – has given rise to modern newborn screening.
Here, I describe how this revolution in metabolomics and clinical diagnostics all started with the analysis of amino acids and acylcarnitines 20 years ago.
Determination of L-carnitine and its derivatives is the basis for newborn screening for several potentially deadly metabolic disorders – a prime example of how analytical science affects all our lives, from the day we are born.
L-carnitine is unique and fascinating molecule. With some chemical similarity to amino acids (perhaps even an ancient precursor to amino acids – see “The Primordial Group” below), L-carnitine is a quaternary ammonium compound – a rare class in the human body. It plays a crucial role in fat metabolism, helping to break down fatty acids (through beta oxidation) into a form that the mitochondria – the cell’s powerhouse – can use as fuel.
Beta oxidation is facilitated by coenzyme A, but coenzyme A and its acyl-bound fatty acids (acyl-CoAs) cannot always cross the mitochondrial membrane. Short- or medium-chain acyl-CoAs can traverse the membrane, but very-long-chain acyl-CoAs cannot, so they must be temporarily transferred to another substrate for transport across the membrane via a translocase “tunnel.” L-carnitine is that substrate. Figure 1 shows how L-carnitine transports fatty acids through the inner mitochondrial membrane in the form of acylcarnitine. Once inside the mitochondria, the fatty acids are transferred back to coenzyme A for delivery to beta oxidation enzymes. Using a train analogy, coenzyme A can be thought of as a small engine moving a few train cars at a time around a rail yard, while L-carnitine is a bulkier locomotive that can pull longer trains over greater distances.
Read the full article now
Log in or register to read this article in full and gain access to The Analytical Scientist’s entire content archive. It’s FREE!
Or register now - it’s free!
You will benefit from:
- Unlimited access to ALL articles
- News, interviews & opinions from leading industry experts
- Receive print (and PDF) copies of The Analytical Scientist magazine
- RH Clark et al., “Impact of L-carnitine supplementation on metabolic profiles in premature infants”, J Perinatol, 37, 566-571 (2017).