Carnitine and Acylcarnitines - Reuter 2012 - NATALIA Flashcards
What is the normal acylcarnitine to L-carnitine ratio?
0.25
What acylcarnitine to L-carnitine ratio is considered abnormal?
Greater than 0.4
What effect does a vegetarian diet have on carnitine levels? How does this affect urinary excretion?
Vegetarian diets don’t result in significant deficit of carnitine. Urinary excretion of carnitine is lower in vegetarians, which suggests compensatory mechanisms.
How are orally ingested L-carnitine and its short-chain acyl derivatives absorbed? What happens to unabsorbed carnitine? How does absorption efficiency correlate with oral carnitine content?
- Taken up from small intestinal lumen into enterocytes via a 2-component system: saturable system via OCTN2 transporters and passive diffusion.
- Unabsorbed carnitine is degraded in large intestine and excreted in feces.
- Efficiency of absorption decreases as dietary content increases.
How much carnitine is from de novo biosynthesis in omnivorous humans? vegetarians?
25% and 90% respectively
In which organs are the enzymes required for carnitine biosynthesis? How much relative enzyme activity is in these organs?
Liver, kidneys and brain.
Activity in kidney is 3x that in the liver and 6x that in the brain.
Which amino acids are required for synthesis of carnitine?
Lysine and methionine
What is the total body content of L-carnitine (in a healthy 70kg male)? Where is the carnitine found?
Total body L-carnitine is 130 mmol: 0.5% in extracellular fluid, 0.1% in plasma, 0.4% in heart, 0.2% in kidney, 97% in skeletal muscle, some amount in RBCs.
What is the primary route of carnitine elimination?
Primary route of elimination is via renal excretion. Carnitine is a small, polar molecule that does not undergo protein binding and is freely filtered at the glomerulus. 95% is reabsorbed at proximal tubule, but at high plasma carnitine concentration, absorption is decreased due to saturation kinetics. L-carnitine is preferentially reabsorbed over its over its esters.
What is the volume of distribution of IV carnitine immediately after administration?
7-14L, which is equivalent to volumes of extracellular compartment. Concentration declines following administration in a multiexponential manner as carnitine gets taken up into the muscle.
