Abstract
Carnitine plays essential roles in intermediary metabolism. In non-vegetarians, most of carnitine sources (~75%) are obtained from diet whereas endogenous synthesis accounts for around 25%. Renal carnitine reabsorption along with dietary intake and endogenous production maintain carnitine homeostasis. The precursors for carnitine biosynthesis are lysine and methionine. The biosynthetic pathway involves four enzymes: 6-N-trimethyllysine dioxygenase (TMLD), 3-hydroxy-6-N-trimethyllysine aldolase (HTMLA), 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABADH), and γ-butyrobetaine dioxygenase (BBD). OCTN2 (organic cation/carnitine transporter novel type 2) transports carnitine into the cells. One of the major functions of carnitine is shuttling long-chain fatty acids across the mitochondrial membrane from the cytosol into the mitochondrial matrix for β-oxidation. This transport is achieved by mitochondrial carnitine–acylcarnitine cycle, which consists of three enzymes: carnitine palmitoyltransferase I (CPT I), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT II). Carnitine inborn errors of metabolism could result from defects in carnitine biosynthesis, carnitine transport, or mitochondrial carnitine–acylcarnitine cycle. The presentation of these disorders is variable but common findings include hypoketotic hypoglycemia, cardio(myopathy), and liver disease. In this review, the metabolism and homeostasis of carnitine are discussed. Then we present details of different inborn errors of carnitine metabolism, including clinical presentation, diagnosis, and treatment options. At the end, we discuss some of the causes of secondary carnitine deficiency.
Highlights
Carnitine (l-3-hydroxy-4-N,N,N-trimethylaminobutyrate), is an essential water soluble molecule that has many biological functions
One of the major functions of carnitine is shuttling long-chain fatty acids across the mitochondrial membrane from the cytosol into the mitochondrial matrix for β-oxidation. This transport is achieved by mitochondrial carnitine–acylcarnitine cycle, which consists of three enzymes: carnitine palmitoyltransferase I (CPT I), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT II)
Carnitine inborn errors of metabolism could result from defects in carnitine biosynthesis, carnitine transport, or mitochondrial carnitine–acylcarnitine cycle
Summary
Carnitine (l-3-hydroxy-4-N,N,N-trimethylaminobutyrate), is an essential water soluble molecule that has many biological functions. Endogenous synthesis provides the majority (>90%) of total carnitine in strict vegetarians, in whom dietary intake provides less than 0.1 μmol/Kg/day of carnitine [9,10,11]. Normal plasma free carnitine levels are low, ranging between 25–50 μmol/L [12]. Normal carnitine levels are maintained by balance between dietary intake, endogenous synthesis, and renal reabsorption. The kidneys are very efficient in maintaining normal levels of plasma carnitine by modulating urinary carnitine excretion according to the intake from diet [14]. Carnitine inborn errors of metabolism (IEM) can be divided into disorders of carnitine biosynthesis, carnitine transport, and mitochondrial carnitine–acylcarnitine cycle The presentation of these disorders is variable but common findings include hypoketotic hypoglycemia, cardio(myopathy), and liver disease. Secondary carnitine deficiency could develop in several IEM, as a side effect of some drugs, or due to increased excretion with tubular dysfunction or dialysis
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