FA Oxidation and Ketone Bodies Flashcards
FA oxidation occurs where?
in mitochondria
True or false? Long-chain FAs can’t enter the mitochondria without transport mechanisms. Medium and short-chain FAs can enter by diffusion.
true
Medium-chain and short-chain FAs are more water soluble. They are not incorporated into ____. They enter the portal blood and are transported primarily to the ____ where they enter by _____.
chylomicrons; liver; diffusion
In the mitochondria, medium and short-chain FAs are activated to ___-___ for beta-oxidation
acyl-CoAs
FA binding proteins in the plasma membrane aid in the transport of long-chain FAs from ___ in the blood
albumin
Long-chain FAs enter the mitochondria as fatty _____
acylcarnitines
A fatty acyl-CoA synthase on the ___ mitochondrial membrane produces acyl-CoAs which enter the mitochondrial ____-membrane space
outer; inter
note: CPT I catalyzes this reaction
_____ are transported across the mitochondrial inner membrane in exchange for “free” _____ by cranitittine:acylcarnitine translocase
acylcarnitines; carnitine
Inside the mitochondria, the acyl-CoA is “____” by CPT II
“regenerated”
Beta-oxidation of long-chain acyl-CoAs is a series of 4 reactions repeated cyclically. Each cycle produces how many acetyl-Coa, FADH2, NADH, and acyl-CoA
acetyl-CoA: 1
FADH2: 1
NADH: 1
acyl-CoA: one reduced in length by 2 carbons
Since the 4 reactions of beta-oxidation occur inside the mitochondria, the reduced cofactors are substrates for ____ ____, and the acetyl-CoA is a substrate for the ____ ____
oxidative phosphorylation; TCA cycle
Each of the 4 reactions in beta-oxidation is catalyzed by a number of enzymes which have various specificities for chain length. For the following acyl-CoA dehydrogenase, give the light of chain it prefers. VLCAD LCAD MCAD SCAD
VLCAD: prefers C12 to C24
LCAD: C12 to C16
MCAD: C6 and C8
SCAD: C4>C6>C8
The major control of beta-oxidation is exerted at which enzyme?
CPT I
CPT I is inhibited by ____-___
malonyl-CoA
Malonyl-CoA is the produce of ___-___ carboxylase and is the substrate for FA ____
acetyl-CoA; synthesis
Acetyl-CoA carboxylase is stimulated (malonyl-CoA is produced) in what situation?
when insulin predominates
Acetyl-CoA carboxylase is inhibitied (malonyl-CoA concentration decreases) in what situation?
when glucagon predominates
How do odd-numbered FAs go through Beta-oxidation?
- at the final stage, one molecule of acetyl-CoA and one molecule of propionyl-CoA are produced
- propionyl-CoA is converted to succinyl-CoA
____-___ is a gluconeogenic precursor, and thus the only part of a FA which can result in the net synthesis of glucose
Succinyl-CoA
Oxidation of unsaturated FAs have to be handled differently because the double bonds are in the ____ configuration and may involve an ___-numbered carbon
cis; odd
Unsaturated FAs are oxidized with help from two enzymes. What are they?
- enoyl-CoA isomerase
2. 2,4-dienoyl-CoA reductase
Where does oxidation of very long chain FAs (C24-C26) occur?
peroxisomes
note: called “modified” beta-oxidation
What are the products of very long chain FA “modified” beta oxidation?
acetyl-CoA and a fatty acyl-CoA reduced by 2 carbons
The acyl-CoA oxidation in modified beta oxidation is not linked to cofactor ____
reduction; means no energy is provided by this step
The peroxisomal oxidation (modified beta oxidation) proceeds until the acyl-CoA is about ___ carbons long
8
The octanoyl-CoA and the acetyl-CoA produced by peroxisomal oxidation are transported to the ____ for further oxidation
mitochondria
True or false? animals do not produce branched-chain fatty acids
true
The most common long-chain branched FA is a degradation product of ____
chlorophyll
long-chain branched FAs are oxidized where?
peroxisomes
What are the products of long-chain branched FA oxidation?
- CO2
- propionyl-CoA
- acetyl-CoA
In regards to w-oxidation of FAs, the w-carbon is the terminal ___ group of the FA
methyl
w-oxidation occurs where? requires what?
occurs in ER
requires cytochrome P450, O2, and NADPH
The w-CH3 group is oxidized first to an ____ and then to a ____ ___
alcohol; carboxylic acid
note: produces a dicarboxylic acid
The w-oxidation pathway is though to function to produce more water-soluble compounds from water insoluble FAs. The products may be oxidized as ___-chain FAs or they can be ___
medium; excreted
Ketone bodies are formed from ___-___ from FA oxidation
acetyl-CoA
Name the 3 ketone bodies
acetoacetate, beta-hydroxybutyrate; acetone
The ketone bodies are synthesized in ____ ____
liver mitochondria
___-___ is an intermediate in the ketone body pathway
HMG-CoA
The liver mitochondrial HMG-CoA synthase is an isozyme restricted to the mitochondria and functions only in what?
synthesis of ketone bodies
The cytosolic HMG-CoA synthase of many cells is the isozyme of ____ synthesis
cholesterol
Ketone bodies are utilized by peripheral tissues for energy - primarily the ___ and ____
muscle and brain
note: the enzymes are mitochondrial
The ___ only produces ketone bodies, and the ___ ___ only utilizes ketone bodies
liver; peripheral tissue
Only liver mitochondria contain the enzymes specific for the synthesis of ketone bodies. What are they?
- mitochondrial HMG-CoA synthase
2. HMG-CoA lyase
Peripheral tissues (muscle and brain) express the enzyme specific for utilization of ketone bodies. What is it?
acetoacetate: succinyl-CoA transferase
True or false? ketone bodies are formed in the liver only when the liver is supplied with high concentrations of FAs
true
Where do the FAs used to synthesize ketone bodies come from?
lipolysis of adipose tissue
In what individuals is ketone body production usually seen?
starving or uncontrolled type 1 diabetes
After an over night fast, the concentration of ketone bodies in the blood is on the order of ____ mM. After a 2 day fast? After 40 days of starvation?
overnight: 0.05
2 days: 2mM
40 days: 7mM
____ is derived from the spontaneous, non-enzymatic decarboxylation of acetoacetate
acetone
The amount of FAs provided to the liver is under the control of ____ and ____
insulin and glucagon
This is the most common genetic disease of lipid metabolism (1/15000). It is associated with non-ketotic hypoglycemia upon fasting, fatty infiltration of liver, and short chain dicarboxylic acids in urine
MCAD (medium-chain acyl-CoA dehydrogenase) deficiency
In regards to MACD, non-ketotic hypoglycemia upon fasting may be deadly in an overnight fast of which individuals?
children
In regards to MACD, Fatty acids which cannot be oxidized are assembled into ____ which exceed the ability of the liver to secrete as ___
TAG; VLDL
In regards to MACD, the short chain dicarboxylic acids in the urine arise from where?
w-ocidation of medium and short chain fAs which can’t be oxidized by beta-oxidation
What is the treatment of MACD?
avoid fasting
In this disorder of lipid oxidation, insufficient FAs are delivered into the mitochondria. Symptoms include non-ketotic hypoglycemia due to decreased energy for gluconeogenesis
carnitine deficiency
In this disorder of lipid oxidation, symptoms include non-ketotic hypoglycemia due to decreased beta-oxidation, hepatomegaly with fatty infiltration, increased plasma carnitine. It can be overcome by medium-chain FAs
CPT I deficiency
This disorder of lipid oxidation can be described by a rare genetic deficiency of a component required for peroxisomal oxidation of branched-chain FAs. Its associated with serious neurological issues.
Refsum disease
How is Refsum disease treated?
by reducing phytanic acid from diet (restrict dairy and meat)
This disorder of lipid oxidation is due to eating the unripe fruit of the akee tree, which contains hypoglycin - It is a potent inhibitor of acyl-CoA dehydrogenase. Symptoms are non-ketotic hypoglycemia
Jamaican vomitting sickness
note: one case reported a blood glucose concentration of 3 mg/dl
