Podcast
Questions and Answers
What is the primary role of glyceroneogenesis in adipose cells during starvation?
What is the primary role of glyceroneogenesis in adipose cells during starvation?
What effect do thiazolidinediones have on insulin resistance?
What effect do thiazolidinediones have on insulin resistance?
Which of the following is a common target for cholesterol-lowering drugs?
Which of the following is a common target for cholesterol-lowering drugs?
What are the main fates of cholesterol synthesized in the liver?
What are the main fates of cholesterol synthesized in the liver?
Signup and view all the answers
What is the function of bile acids like taurocholic acid in digestion?
What is the function of bile acids like taurocholic acid in digestion?
Signup and view all the answers
In which organ is most cholesterol synthesized in vertebrates?
In which organ is most cholesterol synthesized in vertebrates?
Signup and view all the answers
What is the primary product of the seven cycles of condensation, reduction, dehydration, and reduction in fatty acid synthesis?
What is the primary product of the seven cycles of condensation, reduction, dehydration, and reduction in fatty acid synthesis?
Signup and view all the answers
What is the initial precursor for the biosynthesis of isoprenoids and cholesterol?
What is the initial precursor for the biosynthesis of isoprenoids and cholesterol?
Signup and view all the answers
How does acetyl-CoA enter the cytosol for fatty acid synthesis?
How does acetyl-CoA enter the cytosol for fatty acid synthesis?
Signup and view all the answers
Which receptor is stimulated by thiazolidinediones to regulate fat metabolism?
Which receptor is stimulated by thiazolidinediones to regulate fat metabolism?
Signup and view all the answers
Which pathway primarily contributes to the production of glycerol 3-phosphate for triglyceride synthesis?
Which pathway primarily contributes to the production of glycerol 3-phosphate for triglyceride synthesis?
Signup and view all the answers
What is the role of phosphatidic acid in lipid metabolism?
What is the role of phosphatidic acid in lipid metabolism?
Signup and view all the answers
Which of the following is a major contributor to the reducing power (NADPH) needed for fatty acid synthesis?
Which of the following is a major contributor to the reducing power (NADPH) needed for fatty acid synthesis?
Signup and view all the answers
What could be a consequence of an excessive dietary ratio of ω-6 to ω-3 fatty acids?
What could be a consequence of an excessive dietary ratio of ω-6 to ω-3 fatty acids?
Signup and view all the answers
What determines the classification of lipoprotein particles?
What determines the classification of lipoprotein particles?
Signup and view all the answers
Which enzyme is responsible for converting phosphatidic acid to diacylglycerol?
Which enzyme is responsible for converting phosphatidic acid to diacylglycerol?
Signup and view all the answers
Which lipoprotein contains the highest amount of cholesterol?
Which lipoprotein contains the highest amount of cholesterol?
Signup and view all the answers
How does insulin affect fatty acid synthesis in the body?
How does insulin affect fatty acid synthesis in the body?
Signup and view all the answers
What is the primary function of HDL in lipid transport?
What is the primary function of HDL in lipid transport?
Signup and view all the answers
How do elevated levels of LDL affect cellular cholesterol uptake?
How do elevated levels of LDL affect cellular cholesterol uptake?
Signup and view all the answers
Which lipoprotein is primarily responsible for transporting triglycerides?
Which lipoprotein is primarily responsible for transporting triglycerides?
Signup and view all the answers
What is the role of LDL in cholesterol metabolism?
What is the role of LDL in cholesterol metabolism?
Signup and view all the answers
Which condition is associated with increased levels of VLDL and LDL?
Which condition is associated with increased levels of VLDL and LDL?
Signup and view all the answers
What happens to cholesterol when HDL is taken up by the liver?
What happens to cholesterol when HDL is taken up by the liver?
Signup and view all the answers
Which of the following fatty acids can help lower blood cholesterol levels?
Which of the following fatty acids can help lower blood cholesterol levels?
Signup and view all the answers
What is a known mechanism by which Omacor® operates?
What is a known mechanism by which Omacor® operates?
Signup and view all the answers
What is the best predictor of coronary heart disease in relation to lipoprotein levels?
What is the best predictor of coronary heart disease in relation to lipoprotein levels?
Signup and view all the answers
Which medication functions as an HMG-CoA reductase inhibitor?
Which medication functions as an HMG-CoA reductase inhibitor?
Signup and view all the answers
Which is a fate of cholesterol after its biosynthesis?
Which is a fate of cholesterol after its biosynthesis?
Signup and view all the answers
What enzyme is primarily involved in the biosynthesis of triglycerides?
What enzyme is primarily involved in the biosynthesis of triglycerides?
Signup and view all the answers
What natural product is important for the formation of steroid hormones derived from cholesterol?
What natural product is important for the formation of steroid hormones derived from cholesterol?
Signup and view all the answers
Which agent is known to absorb bile acids to increase cholesterol conversion to bile acids?
Which agent is known to absorb bile acids to increase cholesterol conversion to bile acids?
Signup and view all the answers
What is the primary outcome of fatty acid catabolism?
What is the primary outcome of fatty acid catabolism?
Signup and view all the answers
In which part of the cell does fatty acid biosynthesis occur in animals?
In which part of the cell does fatty acid biosynthesis occur in animals?
Signup and view all the answers
Which molecule is required as a reducing power for fatty acid biosynthesis?
Which molecule is required as a reducing power for fatty acid biosynthesis?
Signup and view all the answers
What is the role of Acyl Carrier Protein (ACP) in fatty acid synthesis?
What is the role of Acyl Carrier Protein (ACP) in fatty acid synthesis?
Signup and view all the answers
What inhibits the formation of malonyl-CoA?
What inhibits the formation of malonyl-CoA?
Signup and view all the answers
How many acetyl-CoA molecules are required to synthesize one molecule of palmitate (16:0)?
How many acetyl-CoA molecules are required to synthesize one molecule of palmitate (16:0)?
Signup and view all the answers
What does fatty acid synthase primarily produce?
What does fatty acid synthase primarily produce?
Signup and view all the answers
What is the substrate for the reaction catalyzed by acetyl-CoA carboxylase (ACC)?
What is the substrate for the reaction catalyzed by acetyl-CoA carboxylase (ACC)?
Signup and view all the answers
Study Notes
Fatty Acid and Lipid Biosynthesis
- Fatty acid and lipid biosynthesis occurs in several passes, processing one acetate unit at a time
- The acetate is activated into malonyl-CoA
- Acetyl-CoA + CO2 + ATP → malonyl-CoA + ADP + P
- Biotin is necessary for this reaction
- Insulin stimulates the conversion of dietary carbohydrates and proteins to fats
- Insulin promotes the process of Acetyl-CoA production
Catabolism and Anabolism of Fatty Acids
- Fatty acid catabolism produces acetyl-CoA and reducing power (NADH, FADH2)
- Fatty acid catabolism takes place in the mitochondria
- Fatty acid anabolism requires acetyl-CoA and malonyl-CoA
- Fatty acid anabolism needs reducing power from NADPH for fatty acid synthesis
- The anabolism of fatty acids takes place in the cytosol in animals and chloroplast in plants
Overview of Fatty Acid Synthesis
- Fatty acids are built in several passes, processing one acetate unit at a time.
- The acetate is derived from activated malonate in the form of malonyl CoA
- The process of making malonyl CoA uses acetyl CoA carboxylase (ACC)
Fatty Acid Synthase Makes Palmitate
- Fatty acid synthase functions in a repeating 4-step sequence
- The chain elongates by two atoms each time
- Vertebrates have a single polypeptide chain with several catalytic domains
- The product of fatty acid synthase is palmitate 16:0
Acyl Carrier Protein (ACP)
- ACP contains a covalently attached prosthetic group, 4'-phosphopantetheine
- ACP has a flexible arm that tethers acyl chains
- ACP carries intermediates between enzyme subunits
- ACP delivers acetate or malonate to the fatty acid synthase
- ACP shuttles the growing chain between active sites during the four-step reaction
Stoichiometry of Palmitate (16:0) Synthesis
- 7 acetyl-CoA molecules are carboxylated to 7 malonyl-CoA molecules
- Seven cycles of condensation, reduction, dehydration, and reduction, use NADPH
- The final product is palmitate (16 carbons), formed from 8 acetyl-CoA, 7 ATP, 14 NADPH and 14 H+
- The byproducts are 7 CO2, 8 CoA, 14 NADP+, 7 ADP, 7 Pi, and 6 H2O.
Pathways for NADPH Production
- NADPH is produced in the cytosol for fatty acid synthesis.
- NADPH is obtained from the malic enzyme and pentose phosphate pathway
- Malic enzyme, takes pyruvate, converts it into malate, producing CO2 and NADPH
- Pentose phosphate pathway produces NADPH during the conversion of glucose-6-phosphate to ribose- 5-phosphate
Acetyl-CoA Is Transported into the Cytosol
- Acetyl-CoA made in the mitochondria is transported to the cytosol as citrate
- Acetyl-CoA combines with oxaloacetate to form citrate
- Citrate is transported into the cytosol where it is oxidized to acetyl-CoA and oxaloacetate
FAS Anabolism/Synthesis & Catabolism/ß-oxidation
- Insulin stimulates fatty acid synthesis and promotes fatty acid catabolism.
- Factors that affect the flux through pathways are the hormonal state and major tissue site
- Subcellular location varies between these two processes
- Oxidation and reduction factors (cofactors) and type of "two-carbon donors/products"
Routes of Synthesis of Unsaturated Fatty Acids
- The ratio of -6 fatty acids to -3 fatty acids in diet is important, and excess can lead to cardiovascular disease.
- Essential fatty acids, such as Omega-6 and Omega-3 fatty acids, must be obtained from the diet
Synthesis of Backbone of TAGS (Fats) and Phospholipids
- Glycerol 3-phosphate is derived from dihydroxyacetone phosphate (DHAP) from glycolysis
- Glycerol 3-phosphate dehydrogenase converts DHAP into glycerol 3-phosphate
- Some glycerol 3-phosphate is synthesized from glycerol via glycerol kinase (minor pathway)
Synthesis of Phosphophatidic Acid
- Phosphatidic acid is a precursor for TAGs and phospholipids
- Fatty acids are attached to phosphatidic acid by acyl transferases
- Phosphatidic acid is important in the biosynthesis of TAGs and phospholipids
- The advantage is that phosphatidic acid then can be made into triacylglycerol or phospholipid.
Phosphatidic Acid Modification
- Phosphatidic acid phosphatase (lipin) removes the 3-phosphate group from phosphatidic acid, which yields 1,2-diacylglycerol
- The third carbon on the 1,2-diacylglycerol is acylated with a third fatty acid to produce triacylglycerol
Insulin Stimulates Conversion of Dietary Carbohydrates and Proteins to Fats
- Insulin promotes the conversion of dietary carbohydrates and amino acids into acetyl-CoA
- This acetyl-CoA is then utilized in the synthesis of fats and triacylglycerols.
Triacylglycerol Cycle
- The Triacylglycerol cycle is important in starvation
- The process involves the breakdown of triacylglycerols in adipose tissue to release fatty acids and glycerol.
- Glycerol is converted to glycerol 3-phosphate, supplying precursors for gluconeogenesis and fatty acid synthesis
- Fatty acids are transported to other tissues for energy production
Glyceroneogenesis
- Glyceroneogenesis is similar to gluconeogenesis
- It is active in adipose cells
- During lipolysis (stimulated by glucagon or epinephrine), glycolysis is inhibited
- DHAP is not readily available to make glycerol 3-phosphate
- Adipose cells do not have glycerol kinase, so they make DHAP via glyceroneogenesis.
Thiazolidinediones
- Thiazolidinediones ("insulin sensitizers") decrease insulin resistance, a phenomenon associated with high blood levels of free fatty acids and obesity-related type 2 diabetes.
- They are stimulators of PPAR (peroxisome proliferation activated receptor), a nuclear receptor that regulates the expression of genes involved in fat metabolism.
Biosynthesis of Isoprenoids and Cholesterol
- Isoprenoids and cholesterol are synthesized from acetyl-CoA via mevalonate and squalene
- The process involves a series of enzymatic reactions starting with acetyl-CoA
- Mevalonate is a key intermediate in the synthesis of isoprenoids and cholesterol.
- Squalene is an intermediate molecule in the production of cholesterol
Formation of Mevalonate from Acetyl-CoA
- Three acetyl-CoA molecules condense to from HMG-CoA
- HMG-CoA reduces to form mevalonate
- HMG-CoA reductase is a target of statins, cholesterol-lowering drugs.
Fates of Cholesterol After Synthesis
- Most cholesterol synthesized in the liver is exported
- Cholesterol is exported as bile acids, biliary cholesterol, or cholesteryl esters
- Bile is stored in the gall bladder and secreted after meals
- Bile acids emulsify dietary fats by surrounding droplets of fats, increasing their surface area for attack by lipases
- Cholesterol is converted into other compounds, such as steroid hormones
Four Major Classes of Lipoprotein Particles
- Lipoprotein particles are named based on sedimentation (density) in a centrifuge
- TAG is less dense than water, hence as TAG % increases, density decreases
- The composition varies between class
- The particles include chylomicrons, VLDL, LDL, and HDL
Cholesterol Uptake by Receptor-Mediated Endocytosis
- LDL receptor binds apoB-100, initiates endocytosis, and internalizes LDL
- LDL receptor is segregated to vesicles, recycled to surface for further LDL binding and receptor-mediated endocytosis
- Lytic enzymes degrade apoB-100 and cholesteryl esters releasing amino acids, fatty acids and cholesterol
Blood Lipoproteins
- Blood lipoproteins transport TG and cholesterol from one tissue to another.
- Chylomicrons and VLDL carry TG's; lipoprotein lipase degrades TGs.
- Elevated VLDL and LDL (or both) are indicators of potential cardiovascular issues
Regulation of Cholesterol Metabolism
- Cholesterol metabolism is regulated by various factors including insulin and glucagon.
- Insulin promotes cholesterol synthesis, while glucagon inhibits it
- AMPK inhibits HMG-CoA reductase (a cholesterol biosynthesis key enzyme)
Steroid Hormones Derived from Cholesterol
- Steroid hormones are derived from cholesterol.
- Pregnenolone is a precursor to progesterone, cortisol, corticosterone, testosterone, and estradiol
- These hormones affect various physiological processes such as metabolism, immune response, and reproduction.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz covers the processes of fatty acid and lipid biosynthesis, focusing on the roles of acetate, malonyl-CoA, and the influence of insulin. Learn about both the anabolic and catabolic pathways involved in fatty acid metabolism including their enzymatic requirements and locations within cells.
