Fatty Acid Oxidation & Ketone Body Metabolism Flashcards
what mobilizes fatty acids?
hormone sensitive lipase
what activates hormone sensitive lipase?
glucagon and epinephrine
where does oxidation of fatty acids occur?
matrix of the mitochondria
what is carnitine synthesized by in the liver?
lysine and methionine
What does each round of beta-oxidation produce?
a NADH+H+, a FADH2, and acetyl coA
Where does oxidation occur?
between the alpha and beta carbon
to break a Nchain fatty acid, how many spirals is it?
(N/2)-1
how many spirals does each ATP use?
5
what does the final spiral of B-oxidation of odd-chain length fatty acids yield?
propionyl CoA
a deficiency of B12 leads to what?
increased levels of methylmalonyl CoA
what is a negative allosteric modulator of carnitine palmitoyl transferase I?
malonyl coA
in a well fed state, what does insulin do
it keeps acetyl coA carboxylase active and increases malonyl coA
during fasting and starvation, what does glucagon do?
it causes lipoylsis and increases fatty acids which inhibits acetyl coA carboxylase
(1) autosomal recessive
(2) impairs oxidation of medium chain fatty acids (C8-C12)
(3) accumulation of medium chain fatty acids and esters in tissues
(4) spillover of C8-C12 acylcarnitine species in blood
(5) hypoglycemia during fasting due to lack of ATPs
(6) decreased gluconeogenesis and ketone body formation
(7) non-ketotic hypoglycemia and block in hepatic beta-oxidation
(8) lethargy, coma, and death if untreated
(9) treated by IV glucose, prevented with frequent feeding, high carb, low fat diet
MCAD Deficiency
(1) inherited (autosomal recessive) or acquired
(2) mutation in genes for Carnitine Palmitoyl Transferase I or II
(3) low protein diet, impaired synthesis of carnitine in liver disease, loss of carnitine during hemodialysis process
(4) decreased LCFA metabolism leads to accumulation of LCFAs in tissues and wasting of acyl-carnitine in urine
(5) Symptoms: cardiomyopathy, skeletal muscle myopathy, encephalopathy, impaired liver function, muscle ache and weakness, rhabdomyolysis and myoglobinuria upon exercise
(6) treated with IV glucose and cease of muscle activity
Carnitine Deficiency
(1) autosomal recessive
(2) mutation in PEX genes encoding for peroxins
(3) accumulation of VLCFAs and BCFAs that are normally degraded in peroxisomes
(4) Symptoms: liver and kidney dysfunction, hepatomegaly, high levels of copper and iron in blood, severe neurologic defects, hypomyelination, craniofacial and skeletal malformations
Zellweger Syndrome
(1) autosomal recessive
(2) deficiency of peroxisomal phytanic acidhydroxylase
(3) impaired-oxidation of phytanic acid
(4) buildup of phytanic acid and derivatives in plasma and tissues
(5) cerebellar ataxia, retinitis pigmentosa, chronic polyneuropathy
(6) treated with low-phytanic acid diet
Refsum Disease
(1) caused by ingestion of unripe Ackee fruit which contains hypoglycin A
(2) hypoglycin A is metabolized to methylenecyclopropylacetic acid (MCPA)
(3) MCPA interferes with transport of LCFAs into mitochondria and inhibits acyl-CoA dehydrogenases involved in beta-oxidation
(4) decrease in ATPs and gluconeogenesis
(5) severe vomiting 2-6 hours after ingestion, severe hypoglycemia, convulsions, coma, death
Jamaican Vomiting Sickness
when does ketone body synthesis occur?
during periods of starvation and low insulin levels
Which ketone body is volatile?
acetone
Which ketone bodies are water soluble?
acetoacetate and beta-hydroxybutyrate
(1) low insulin/glucagon ratio stimulates excess beta-oxidation depleting NAD+ and saturating TCA cycle with acetyl CoA shunting acetyl CoA toward ketone body formation
(2) acetoacetic acid and 3-hydroxybutyric acid (ketone bodies) accumulate in blood and decrease pH
(3) acetone is volatile and hence exhaled giving fruit odor to breath
Diabetic Ketoacidosis
What does Active hormone sensitive lipase do?
It breaks triacylglycerol to di- and mono- acylglycerol, releasing FAs
What does monoacylglycerol lipase do?
it acts on monoalcylglycerol to release FAs and glycerol
