Flashcards in Fatty Acid Oxidation Deck (29):
What are the two most common disorders of fatty acid oxidation?
Carnitine deficiency and MCAD deficiency
True or false: all fatty acids need to be acylated (by fatty acyl co-a synthetase) to get into mitochondrial intermembrane space.
False. Only long-chain fatty acids do; short- and medium-chain fatty acids can diffuse across the mitochondrial membrane.
What inhibits carnitine acetyltransferase 1 and carnitine palmitoyltransferase 1?
Malonyl co-a. Think about it: malonyl co-a is a product in the synthesis of fatty acids, so it makes sense that something that signals fatty acid synthesis should inhibit the fatty acid breakdown pathway (otherwise it would be a futile cycle).
In the mitochondria, fatty acids can _____________.
be broken down via beta oxidation to produce acetyl co-a that generates NADH, FADH2, and GTP
Very long chain fatty acids must first be _________________ before going into the mitochondria.
degraded in peroxisomes
Hormone-sensitive lipase is active when ____________.
phosphorylated (because glucagon and epinephrine activate adenylyl cyclase and activate the protein kinase that phosphorylates hormone-sensitive lipase)
Acetyl co-a carboxylase is inhibited when ___________ (a covalent modification).
phosphorylated by the effects of epinephrine and glucagon binding; insulin activates a phosphatase that breaks the phosphate group off and activates this enzyme
Carnitine acetyltransferase binds acetyl groups to fatty acids, which can then ______________.
pass through the inner mitochondrial membrane (carnitine acetyltransferase is in the outer mitochondrial membrane)
Carnitine deficiency leads to massive accumulation of ________________.
fat within the cytosol of hepatocytes
Trace the beta oxidation pathway.
Cis acyl co-a (in mitochondria)
(Acyl co-a dehydrogenase) – generates a trans double bond
Trans acyl co-a
(Enoyl co-a hydratase) – adds H2O across the double bond
(Beta-hydroxy-co-a-dehydrogenase) – oxidizes OH to O=
(Thiolase) – breaks off oxidized group
One molecule of palmitoyl acid can produce _________.
131 molecules of ATP
Odd-numbered chains require ____________.
an extra step that adds a carboxyl group to the three-carbon remainder that ultimately gets put into the TCA cycle at succinyl co-a
Describe Zellweger syndrome.
deficiency in peroxisomal beta-oxidation enzymes, similar to X-linked adenoleukodystrophy
______________ is characterized by increased urinary excretion of carnitine esters, hypoglycemia, low levels of ketones during fasting state, and sleepiness.
Acyl co-a dehydrogenase deficiency (the most common disorder of beta-oxidation)
Beta-oxidation is regulated at the level of _______________.
Ketone bodies are produced in the __________ in the presence of excess _____________.
liver; acetyl co-a
What happens to ketone bodies?
The liver does not have the enzyme to reconvert beta-hydroxybutyrate to acetyl-co-a, but the brain and muscles do. As such, ketones diffuse out to the peripheral tissues and are reconverted to acetyl co-a.
Why do those with T1DM produce ketones?
Lack of insulin leads to activation of hormone-sensitive lipase which creates more fatty acids. The excess fatty acids undergo beta-oxidation and produce excess acetyl co-a, which then leads to ketone conversion.
Qualitatively, what are the four steps of beta-oxidation?
More than ________ percent of fatty acids in the body are stored as triglycerides.
Carnitine palmitoyl transferase is inhibited by ______________.
malonyl co-a (a signal of fatty acid synthesis)
What is produced by the four-step beta oxidation pathway?
1 Acetyl co-a
Medium-chain fatty acyl dehydrogenase deficiency has been associated with ___________.
Describe the process of ketogenesis.
During fatty acid oxidation, the elevated acetyl co-a and NADH lead to inhibition of pyruvate dehydrogenase and activate pyruvate carboxylase (producing oxaloacetate for gluconeogenesis). Additionally, the excess acetyl co-a favors ketone synthesis.
Trace the ketone synthesis pathway.
(HMG co-a lyase)
(3-hydroxybutyrate dehydrogenase) – produces NADH
Ketones are the primary fuel source in ____________.
the cardiac muscle and renal cortex
In order to use ketones, tissues must have ___________ to initiate conversion of 3-hydroxybutyrate to acteyl co-a.
The primary regulated step in fatty acid oxidation is ______________, while ___________ is the rate-limiting step.
hormone-sensitive lipase; CAT-1