Study sets, textbooks, questions
Upgrade to remove ads
Biochemistry Chapter 13 - Biosynthesis and Storage of Fatty Acids
Terms in this set (108)
What is the pathway for fatty acid de novo synthesis called?
Where is lipogenesis located?
The liver, brain, kidney, adipose tissue, mammary gland, cancers
When is the pathway of de novo synthesis primarily active?
Primarily active in situations of excess energy intake - carbohydrates
Where are carbohydrates and amino acids converted into fatty acids?
What are the fatty acids stored as?
triacyclglycerol (TAG - also known as triglyceride) in cellular lipid droplets
What happens when transport of fatty acids to long term storage is not efficient?
TAG will accumulate in the tissue not dedicated for fat storage = ectopic lipid storage
What cellular compartment is lipogenesis occuring in?
What does lipogenesis use as a reductive power?
What is the purpose of SREB1c and SREB1a?
Sterol Regulatory Element Binding Proteins-1 provide a master regulation of the de novo lipogenesis through transcription control
What is SREBP?
An endoplasmic reticulum bound and membrane sensing protein that undergoes proteolytic cleavage that enables its transport to the nucleus
What does SREBP do?
SREBP binds to specific DNA sequences of genes that encode enzymes for lipogenesis
What are fatty acids synthesized from?
What is the first stage of fatty acid synthesis?
Acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase
What is the second stage of fatty acid synthesis?
Elongation of the fatty acid chain in two carbon increments
What allows the elongation of the fatty acid chain?
Fatty acid synthase
What is the committed step of fatty acid synthesis?
Carboxylation of acetyl-CoA to malonyl-CoA
Where is acetyl-CoA mostly derived from?
Where is ACC1 located and what is its purpse?
Located in the cytoplasm and committed to fatty acid synthesis
Where is ACC2 located and what is its purpose?
Located in the mitochondria and regulates fatty acid oxidation
What happens when ACC2 is inhibited?
Reduced generation of malonyl-CoA which in turn is an inhibitor of CPT-1 (carnitine-palmitoyl transferase)
ACC1 is a ___ enzyme with distinct enzymatic and carrier protein function
What does the ACC1 subunits serve as?
Biotin Carboxyl Carrier Protein
ACC1 is synthesized as an ___ protomer form
What do the protomers contain?
Subunits (biotin carboxylase, transcarboxylase, biotin carboxyl carrier protein), biotin molecule, and a regulatory allosteric site
What are the regulatory allosteric sites for?
Binding of citrate or palmitoyl-CoA
What is the end product of the fatty acid biosynthetic pathway?
What is propionyl-CoA used for?
A substrate for the synthesis of fatty acids with an odd number of carbons (not seen in humans)
What do the odd chain fatty acids seen in humans originate from?
Milk fat consumption
Acetyl-CoA carboxylase is subject to ___
The protomers of acetyl-CoA carboxylase polymerize in the presence of what? What does this do?
Citrate or Isocitrate - produces the active form of the enzyme
The polymerization of acetyl-CoA is inhibited by what?
Phosphorylation ___ the enzyme, dephosphorylation ___ the enzyme
Phosphorylation of the enzyme is promoted by what?
Dephosphorylation of the enzyme is promoted by what?
Phosphorylation is also dependent on what?
The activation of the AMP-activated protein kinase (AMPK)
What is activated AMPK?
A sign of cellular depletion of ATP, will inhibit ACC2 and activate malonyl-CoA decarboxylase to alleviate the malonyl-CoA-dependent inhibition of CPT-1 and allow mitochondrial fatty acid oxidation
Dietary ___ and ___ intake also controls acetyl-CoA carboxylase
Carbohydrate and fat
Synthesis of acetyl-CoA carboxylase is upregulated by what?
High carbohydrate/low fat intake
Synthesis of acetyl-CoA carboxylase is downregulated by what?
High fat/low carbohydrate intake or starvation
Fatty acid synthase contains ___ distinct enzyme activities and an ___ ____ ____
7, acyl carrier protein (ACP)
What is the purpose of ACP?
Replaces CoA as the entity that binds to the elongating fatty acid chain
What is pantetheine group?
Flexible arm that makes the molecule being synthesized available to different enzymes in the fatty acid synthetase complex
Fatty acid synthase builds the fatty acid molecule up to how many carbons?
16 carbon length
The reaction proceeds after an initial priming of ___ with ____, a reaction catalyzed by ______ ______
Cysteine- SH, acetyl-CoA, acetyl transacylase
Malonyl-CoA is transferred by what to the -SH residue of the pantetheine group attached to the ACP in the other subunit?
What is the condensing enzyme that catalyzes the reaction between the previously attached acetyl group and the malonyl residue?
What does 3-ketoacyl synthase liberate?
What happens to the 3-ketoacyl group?
Undergoes sequential reduction, dehydration, and reduction again to form saturated acyl-enzyme complex
What is activated by the saturated acyl-enzyme after the 16 carbon chain (palmitate) is formed?
The synthesis of one palmitate molecule requires ___ acetyl-CoA, ___ ATP, ____ NADPH, ____ H+
8, 7, 14, 14
What does the malate shuttle allow?
The recruitment of two-carbon units from the mitochondrion to the cytoplasm
Where is acetyl-CoA generated?
Is acetyl-CoA able to freely cross the inner mitochondrial membrane?
What does the malate shuttle use in order to allow the transfer from the mitochondria to the cytosol?
____ derived from glycolysis is decarboxylated to ____ in the mitochondria and reacts with ____ in the TCA cycle to form ____
Pyruvate, acetyl-CoA, oxaloacetate, citrate
In the cytosol, citrate in the presence of ___ and ___ undergoes cleavage to ____ and ____ by _____ _______
ATP & CoA, acetyl-CoA, oxaloacetate, citrate lyase
The synthesis of fatty acids is also linked to glucose metabolism through what pathway?
Pentose phosphate pathway
The pentose phosphate pathway is the main provider of ____ required for lipogenesis
NADPH is also generated by the NADP+ linked decarboxylation of ___ to ___ by ____ _____
Malate, pyruvate, malic enzyme
Elongation of a fatty acid chain beyond 16 carbons requires what?
Another set of enzymes
____ released from fatty acid synthase becomes a ___ for the synthesis of longer chain fatty acids
Chain elongation occurs by the addition of further two carbon fragments derived from ___?
Where does fatty acid elongation occur?
What multienzyme complex allows for fatty acid elongation?
Fatty acid elongase
The reactions occurring during chain elongation, the fatty acid is attached to ____ rather than ___ in fatty acid synthesis
Very long chain fatty acids are produced where?
Elongation of stearoyl-CoA (C18) in the brain increases during what?
Myelination, producing the fatty acids for synthesis of sphingolipids
Desaturation of fatty acids require what?
What are the two unsaturated fatty acids known as essential fatty acids?
What all does the desaturation system require?
Molecular oxygen, NADH, cytochrome b5
Where does desaturation of fatty acids occur?
The desaturase system in humans is unable to produce double bonds beyond what?
Carbon-9 and w-(terminal methyl) carbon
Where do most desaturation of fatty acids occur?
Between carbon 9 & 10
____ and ____ fatty acids (or their precursors) must be supplied with diet
w-3 and w-6
w-3 and w-6 fatty acids are required for what?
Phospholipid production and synthesis of eicosanoids (C-20), precursors for important molecules (prostaglandins, thromboxanes, and leukotrienes)
How are w-3 and w-6 obtained?
Dietary vegetable oils and meats
Linoleic acid is converted in a series of elongation and desaturation to what?
Arachidonic acid is the precursor for the synthesis of what in humans?
Elongation and desaturation of linolenic acid produce what?
Where is most EPA in the human body derived from?
Fatty acids are stored and transported as what?
Triacylglycerols (TAG) are produced by a pathway involving what?
What is the source of phosphatidic acid in the liver?
In the adipose tissue what is the indirect source of glycerol? Why
Glucose because of the lack of glycerol kinase
The first step from glycerol-3-phosphate is fatty acid acylation by what?
What is the product of the first step from glycerol-3-phosphate?
Lysophosphatidic acid undergoes a second fatty acid acylation by what? To yield what?
Acylglycerol acyltransferase (AGPAT2), phosphatidic acid
Disruptive mutations of ___ lead to inability to form triacylglycerol in adipose tissue
Phosphatidic acid is dephosphorylated by phosphatidic acid phosphatase to form what?
Where does DAG reside?
Smooth endoplasmic reticulum
TAG is formed from DAG by what?
Diacylglycerol acyltransferase (DGAT)
Triacylglycerols produced in the ___ on ____ _____ _____ can only be transiently stored
Liver, smooth ER
Stored TAG is offloaded for export in the form of what?
Very-low density lipoprotein (VLDL)
Once VLDL is released into the bloodstream it is acted upon by what?
Lipoprotein lipase is active against what?
VLDL and chylomicrons
Where is LDL synthesized from?
Where is LDL secreted?
Capillaries of the adipose tissue
The increased synthesis and secretion of LPL is stimulated by what?
The ___ ___ capillary bed also has LPL, but it is inhibited by insulin
How is LPL activated in skeletal muscle?
By its contractions or by adrenergic stimulation
How does insulin help in the liver?
Increases fructose-2,6-bisphoshpate levels, stimulates glycolysis, thus increasing pyruvate production, promotes production of acetyl-CoA --> stimulating TCA cycle = increased citrate = stimulation of acetyl-CoA carboxylase = increase in fatty acid synthesis
Adipose tissue is an active ____ organ
Obesity is characterized by increased _____
Adiposity (# of adipocytes and their fat content)
What hormones do adipocytes produce?
What growth hormones do adipocytes produce?
Vascular endothelial growth factor
What proinflammatory cytokines do adipocytes produce?
TNF-alpha, and IL6
-Fatty acid synthesis and storage are essential components of body energy homeostasis
-Fatty acid synthesis takes place in the cytosol. Its committed step is the reaction catalyzed by acetyl-CoA carboxylase
-Elongation of the fatty acid chain (up to 16 carbons in length) is carried out by the dimeric fatty acid synthase, which possesses several enzymatic activities. Both acetyl-CoA carboxylase and fatty acid synthase are subject to complex regulation
-The malate shuttle facilitates the transfer of two carbon units from the mitochondria to cytoplasm for use in fatty acid synthesis
-The reducing power for fatty acid synthesis in the form of NADPH is supplied by the pentose phosphate pathway and by the malate shuttle
The essential unsaturated fatty acids are linoleic and linolenic acid. Linoleic acid is converted to arachidonic acid, which in turn serves as the precursor of prostaglandins
-Adiposity signals are provided by adipokines, particularly leptin. Insulin is also important in the regulation of food intake
Sets with similar terms
biochem chapter 16 palmer west q2
Biochemistry Exam 3, Lecture 1: Lipid Metabolism
Fatty Acid Synthesis
Other Quizlet sets
Frankenstein Study Guide
SAS 9 Quiz 9