Carnitine Flashcards
dietary sources of carnitine
most foods
red meat
some plant foods
who has carnitine deficiency?
no one!
who has low carnitine levels? do they overcome it?
premature infants, but they make more and grow rapidly
humans have __ carnitine synthesis
humans have endogenous carnitine synthesis
carnitine uses __ and __ transport
carnitine uses active and passive transport
active and passive caritine transport occurs at __ surface of enterocyte, but NOT __
active and passive caritine transport occurs at apical surface of enterocyte, but NOT basal
75% of consumed carnitine is __, the rest is degraded by __ in __
75% of consumed carnitine is absorbed, the rest is degraded by bacteria in large intestine
byproducts of carnitine degradation and how they are excreted
trimethylamine (urine)
gamma-butyrobetaine (feces)
humans synthesize carnitine using __ and __ (both __ amino acids)
humans synthesize carnitine using lysine and methionine (both essential amino acids)
rate of carnitine synthesis is regulated by availabiity of
E-N-trimethyl lysine
final enzyme of L-carnitine synthesis
gamma-butyrobetaine hydroxylasw
gamma-butyrobetaine hydroxylase is abundant in __ and __, but does not exist in __ and __
gamma-butyrobetaine hydroxylase is abundant in liver and testes, but does not exist in cardiac and skeletal muscle
what 2 organs can’t synthesize carnitine
cardiac or skeletal muscle
rate of carnitine biosynthesis is NOT affected by (2)
- dietary intake of carnitine
- changes in renal handling of carnitine (more or less excretion)
carnitine is concentrated in __ tissues, but most abundant in __ and __
carnitine is concentrated in most tissues, but most abundant in liver and muscle
97% of all carnitine is in
skeletal muscle
__ carnitine transporters exist
6 carnitine transporters exist
4 main carnitine transporters
OCTN1
OCTN2
OCTN3
Oat9s
OCTN stands for
organic cation transporter
OCTN1 is found in
most tissues
OCTN1 has __ affinity and is dependent on __
OCTN1 has low affinity and is dependent on pH
OCTN1 is mostly responsible for
secretion of carnitine across renal epithelium
OCTN2 is highly expressed in (7)
heart
muscle
placenta
kidneys
pancreas
testis
epididymic
OCTN2 is weakly expressed in
brain
liver
lung
OCTN2 has __ affinity
OCTN2 has high affinity
OCTN2 is dependent on
Na+ gradient
which OCTN is most important?
OCTN2
except in testes
OCTN3 is highly expressed in
testes
OCTN3 has the highest __ for carnitine
OCTN3 has the highest specificity for carnitine
Oat9s is found in
mice
carnitine and acylcarnitine esters are excreted by __
excretion increases with higher
carnitine and acylcarnitine esters are excreted by kidney
excretion increases with higher concentrations in blood
kidney must __ 95% of carnitine for proper carnitine homeostasis
kidney must reabsorb 95% of carnitine for proper carnitine homeostasis
carnitine in metabolism
mitochondrial LCFA oxidation
carnitine is essential for mitochondrial use of __ and for __ production
carnitine is essential for mitochondrial use of LCFAs and for energy production
carnitne in metabolism 2
acyl-CoA to CoA ratio
which form of CoA is necessary
free CoA (non-esterified)
carnitine can accept __ and __ residues to free __
carnitine can accept acyl and acetyl residues to free CoA
when do we need free CoA
pyruvate dehydrogenase rxns
assessment of carnitine status
plasma ratio of esterified to non-esterified carnitine
high plasma ratio of esterified to non-esterfied indicates
abnormal carnitine metabolism
carnitine deficiency is caused by hyper-__ or decreased __ of carnitine by __
carnitine deficiency is caused by hyper-excretion or decreased reabsorption of carnitine by kidneys
is there a test for functional carnitine deficiency?
no
genetic carnitine deficiency
mutations of OCTN2
OCTN2 symptoms
myopathies
hypoglycemia
hyperammonemia (protein metabolism)
fatal if untreated
hyper-excretion of carnitine
abnormal amounts of SCFA produced and removed from body by excretion as acylcarnitine esters
rate of excretion > endogenous synthesis
prolonged treatment with __ and __ can deplete circulating carnitine levels
prolonged treatment with valproic acid and pivalic acid can deplete circulating carnitine levels
__ agents can also deplete carnitine
chemotherapeutic agents can also deplete carnitine
2 uses or carnitine as a treatment
- in patients with OCTN2 mutation
- end stage renal disease
why is carnitine used as a treatment in end stage renal disease
patients with renal disease have abnormally high ratio of eseterified carnitine to free carnitine
corrected by L-carnitine treatment
in who is carnitine a conditionally essential nutrient?
hospitalized premature infants
