Fatty Acid Metabolism Flashcards
MCAD deficiency is _____ ______ disorder
autosomal, recessive
Name the 3 ketone bodies
acetoacetate
3-hydroxybutyrate
Acetone
Ketone bodies are produced in the
liver mitochondria from Beta-oxidation derived acetyl CoA
________ is/are transported in the blood to peripheral cells/tissues
Acetoacetate and 3-Hydroxybutyrate
____ is a dead-end by-product
Acetone
Peripheral cells convert ___ back into acetyl CoA, a substrate for the TCA cycle
ketone bodies
Ketoacidosis can be caused by _____
fasting
Diabetic Ketacidosis causes
fruity smelling breath from acetone
_____ associated fatty acids serve as major concentrated fuel store for the body
TAG
______: constitutive, low level release of fatty acids from adipose, TAG –> DAG + FA
Adipose lipase
______ has a major role in regulated TAG lipolysis and release of fatty acids from adipose, TAG–>DAG + FA
Hormone-sensitive lipase (HSL)
_______: releases fatty acids from TAG in the circulating lipoprotein particles to free fatty acids and glycerol
-this is a more complete release of FA’s
Lipoprotein Lipase
HSL is phosphorylated and activated by ____________
cAMP dependent protein kinases
Phosphorylation of HSL causes:
1)
2)
1) activates its enzymatic lipase activity
2) HSL binding to perilipin (lipid droplet surface protein)
Insulin promotes dephosphorylation of HSL by _______. This shuts off HSL catalyzed hydrolytic release of fatty acids from TAG
activating phosphatases
_____ can participate in glycolysis or gluconeogenesis
DHAP
Adipocytes lack _____ and cannot metabolize glycerol released in TAG degradation if all FAs are released from a TAG molecule
glycerol kinase
Glycerol is
1)
or
2)
1) released to blood and taken up by liver; phosphorylated in the liver to be used in TAG synthesis
2) reversibly converted to DHAP by glycerol phosphate dehydrogenase
Free fatty acids leave adipocytes to the blood where they bind ____ ____
serum albumin
After binding to serum albumin, the fatty acids are taken up by cells and are activated to CoA by _______
fatty acyl CoA synthetase (thiokinase)
Fatty acyl CoA is oxidized for ______
energy production/release
~50% of free fatty acids released from adipose TAG are resterified to ______. This process functions to decrease the plasma free fatty acid level associated with insulin resistance in type 2 diabetes and obesity
glycerol 3-phosphate
The major pathway for obtaining energy from fatty acids is ______
Beta-oxidation
Beta-oxidation occurs in the ______
mitochondria
For Beta-oxidation, the fatty acid must be in the form of __________
(activated) fatty acyl CoA
Beta-oxidation involves the successive removal of ______. Where are they removed from?
2-carbon fragments; the carboxyl end
What are the products of Beta-oxidation?
Acetyl CoA, NADH, FADH2
__________ is located on the cytosolic side of mitochondrial outer membrane and generates LCFA CoA in the cytosol
Long-chain Fatty Acid CoA synthase (thiokinase)
________ cannot directly cross the inner membrane of the mitochondria due to the presence of the CoA
LCFA CoA
The ________ imports LCFAs into the mitochondria (required)
Carnitine Shuttle Process
In the 1st step of the Carnitine Shuttle Process, acyl groups are transferred from CoA to carnitine by ________, an outer mitochondrial membrane enzyme
Carnitine Acyl Transferase-1 (CAT-1)
In the 2nd step of the Carnitine Shuttle Process, acyl carnitine is transported into the mitochondrial matrix in exchange for free carnitine by _____________
carnitine-acyl carnitine translocase
In the 3rd step of the Carnitine Shuttle Process, ______ on the matrix side of the inner mitochondrial membrane catalyzed acyl group transfer from carnitine to CoA
CAT-II
CAT-1 is inhibited by _____; thus preventing LCFA transfer from CoA to carnitine
malonyl CoA
The inhibition of CAT-1 by malonyl CoA prevents
1)
2)
1) mitochondrial import and beta-oxidation of newly synthesized LCFAs
2) Beta-oxidation of LCFAs to generate energy while in the well-fed state
Name the sources of carnitine.
Diet (primarily in meat products) or synthesized by enzymatic pathway in the liver and kidney using amino acids lysine and methionine
________ houses ~97% of carnitine in the body and must rely on uptake of synthesized and dietary sources from the blood
Skeletal Muscle
Carnitine deficiency reduces the ability of tissues to _________
use LCFAs as a metabolic fuel
What are secondary carnitine deficiencies caused by? (4)
1) decreased synthesis due to liver disease
2) dietary malnutrition or strict vegetarian diet
3) hemodialysis, which removes carnitine
4) conditions when carnitine requirements increase (pregnancy, severe infections, burns, trauma)
Primary Carnitine Deficiencies are caused by congenital deficiencies in: (3)
1) Renal Tubular Reabsorption of Carnitine
2) Carnitine Uptake by Cells
3) CAT-1 or CAT-ll Function
In primary carnitine deficiencies, the genetic defect of CAT-l results in _________, leading to severe hypoglycemia, coma or death
decreased liver use of LCFA during a fast
In primary carnitine deficiencies, the genetic defect of CAT-ll results in the ____ and _____ ______ exhibiting symptoms that range from cardiomyopathy to muscle weakness with myoglobinemia following prolonged exercise
heart and skeletal muscle
What is the treatment for Primary Carnitine Deficiencies?
1) Avoid prolonged Fasts
2) Adopt a diet high in carbs and low in LCGA
3) Supplement with medium-chain fatty acids and carnitine
Acetyl CoA is a positive allosteric effector of ______ ______ linking fatty acid oxidation and gluconeogensis
pyruvate carboxylase
Degrading 1 palmitoyl CoA to CO2 and H2O results in a net of _____ ATP produced
129
The Beta-oxidation of fatty acids w/an odd number of carbons is similar to that of even number of carbons with the exception that the final thiolytic cleavage produces a ___________.
3-Carbon product: propionyl CoA
Propionyl CoA Metabolic Pathway
In step 1, the synthesis of D-methylmalonyl CoA, propionyl CoA is carboxylated by _________
propionyl CoA carboxylase
Propionyl CoA Metabolic Pathway
In step 2, the formation os L-methylmalonyl CoA: D–>L methylmalonyl CoA is an isomer conversion by
methylmalonyl CoA racemase
Propionyl CoA Metabolic Pathway
In step 3, the synthesis of succinyl CoA: the carbons of L-methylmalonyl CoA are rearranged to form succinyl CoA by _____________: succinyl CoA enters TCA cycle
methylmalonyl CoA mutase
_______ requires vitamin B12–the mutase reaction is 1 of 2 reactions in the body requiring vitamin B12
methylmalonyl CoA mutase
_________ deficiency causes excretion of both propionate and methylmalonate in the urine
Vitamin B12
Both heritable methylmalonic acidemia or aciduria is possible, both result in _______ and the potential for ________
metabolic acidosis and developmental retardation
Unsaturated fatty acids release less energy than a similar saturated fatty acid because
1)
2)
1) they are less highly reduced
2) fewer reducing equivalents can be produced
Monounsaturated fatty acids require an additional _________ enzyme for complete oxidation
isomerase
Polyunsaturated fatty acids require an _______ and _______ enzyme for complete oxidation
isomerase and reductase
VLCFA (22 carbons or longer) are initially oxidized in the ______
peroxisome
Peroxisomal Beta-Oxidation does not generate ______
ATP
Once initially oxidized in the peroxisome, the partially oxidized ‘shorter’ carbon chain fatty acid can be imported/diffuse to the __________ for complete oxidation
mitochondrial matrix
This is a peroxisome biogenesis disorder that result in genetic defects resulting in failure to target matrix proteins to the peroxisome
Zellweger Syndrome
This disease causes genetic defects causing the failure to transport VLCFA across the peroxisome membrane.
X-linked adrenoleukodystrophy
Both Zellweger Syndrome and X-linked adrenoleukodystrophy cause ______________________
accumulation of VLCFA in the blood and tissues
Branched-chain, 20 C fatty acid phytanic acid cannot function as a substrate for ________ due to the methyl group at its Beta-carbon
acetyl CoA dehydrogenase
____________ hydroxylates the alpha-carbon and the carbon 1 is released as CO2
Paytanoyl CoA alpha-hydroxylase (PhyH)
19-C _______ is activated to CoA and undergoes Beta-oxidation
pristanic acid
_______ disease:
- rare, autosomal recessive: caused by peroxisomal PhyH deficiency
- phytanic acid accumulates in the blood and tissues
- symptoms are primarily neurologic
- treatment requires dietary restrictions to halt disease progession
Refsum Disease
________ deficiency: decreased oxidation of 6- to 10- C fatty acids
MCAD
What are the symptoms of MCAD deficiency?
Severe hypoglycemia, since the tissues rely on glucose
What is the treatment of MCAD deficiency?
Avoid fasting
_____ deficiency:
- one of the most common inborn errors of metabolism
- the most common inborn error of fatty acid oxidation
- high incidence in Northern Europeans
MCAD
_____ has recently been identified as a possible cause for some incidence of reported sudden infant death syndrome (SIDS) or Reye Syndrome
MCAD
