Biochemistry Final Exam UNE CHEM 1005 (Weeks 9-15) Questions & Answers Solved 100% Correct!!

Biochemistry Final Exam UNE CHEM 1005 (Weeks 9-15) Questions & Answers Solved 100% Correct!! Control of Fatty Acid Synthesis vs. Oxidation When Insulin is HIGH --> fatty acid synthesis occurs When Glucagon is HIGH --> lipolysis, fatty acid B-oxidation, ketogenesis occur **These never happen at the same time! Lipolysis Process of releasing free fatty acids from triacylglycerols stored in the adipose IN THE FASTED STATE Steps of lipolysis 1) Hormone Sensitive Lipase: activated by glucagon and epinephrine TAGs are hydrolyzed into FFAs and glycerol (inhibited by insulin) 2) Long chain FFAs travel bound to albumin to peripheral tissues to be used as energy source 3) Glycerol travels to liver to be used as gluconeogenesis substrate 4) Acyl-CoA Synthetase: can reconvert FFAs to acyl-CoA to be used for re-esterification in the adipose (continuous cycle of lipolysis & re-esterification) Beta Oxidation Process of generating acetyl-CoA, NADH, and FADH2 from the oxidation of FFAs taken up by peripheral tissues (mostly liver & skel. muscle tissue). Happens in mitochondria. Long chain FFAs cannot cross the mito membrane, so a transport system is in place. Ketogenesis Process of generating ketones from excess acteyl-CoA produced from Beta-Oxidation Mitochondrial pathway Ketones can be used as fuel by other tissues but cannot be oxidized by... The liver. Skeletal muscle can oxidize ketones. The brain will oxidize ketones when starving. Ketogenesis is regulated by... 1) Activity of lipolysis 2) Cytosolic levels of malonyl-CoA (which inhibit CPTI) 3) Flux through the TCA depending on NADH levels & concentration of intermediates (especially OAA) Ketoacidosis can occur from prolonged ketogenesis, such as... During starvation and uncontrolled diabetes Important connections between Beta-Oxidation and other pathways 1) It supplies high levels of ATP in the fasted state 2) ATP is required for both process of glucose synthesis via gluconeogenesis & nitrogen disposal via the urea cycle 3) deficiencies in beta-oxidation can result in hypoglycemia due to inability to support glucose synthesis (such as CPTI deficiency, or medium chain acyl-dehydrogenase deficiency) Fatty Acid Synthesis: Activators & Inhibitors Activated by insulin Inhibited by glucagon Fatty acid synthesis takes place in the... Cytosol Fatty acid synthesis: what occurs in the mitochondria? Substrates need to be shuttled out of the mitochondria In the mito: -Acetyl-CoA and OAA in the mito --> citrate -Tricarboxylate transporter --> removes excess citrate from the mito Fatty acid elongation Requires malonyl-CoA, fatty acyl-CoA and NADPH. This pathway determines the chain length for fatty acids (medium, long, etc.) Fatty acid synthesis connection to the PPP PPP provides glycerol (for TAG synthesis) and NADPH (for fatty acid synthesis) Fate of newly synthesized fatty acids -Fatty acids are NOT stored in the liver -instead, they're packaged into VLDL particles as TAGs (along with cholesterol) and are transported to adipose for storage HDL: Origin, Primary Apo Protein, Composition, Primary Role Origin: Liver Primary Apo Protein: ApoA Composition: Cholesterol and Cholesteryl Ester > Triacylglycerol (C and CE > TG) Primary Role: reverse cholesterol transport *HDL is the most dense LDL: Origin, Primary Apo Protein, Composition, Primary Role Origin: Maturation of VLDL Primary Apo Protein: ApoB100 Composition: Cholesterol and Cholesteryl Ester > Triacylglycerol (C and CE > TG) Primary role: cholesterol transport from the liver VLDL: Origin, Primary Apo Protein, Composition, Primary Role Origin: Liver Primary Apo Protein: ApoB100 Composition: Triacylglycerol > Cholesterol and Cholesteryl Ester (TG > C and CE) Primary role: carries newly synthesized TAG from the liver to the adipose Chylomicron: Origin, Primary Apo Protein, Composition, Primary Role Origin: Intestine Primary Apo Protein: ApoB48 Composition: Triacylglycerol > > Cholesterol > Cholesteryl Ester (TG > > C > CE) Primary Role: carries dietary lipids to the adipose for storage *Chylomicrons are the least dense ACAT Acyl-coenzyme A acetyltransferase Esterifies cholesterol within the cell LCAT or PCAT Lecithin cholesterol acyl transferase Esterifies cholesterol in the plasma when moving in and out of HDL particles ABCG1/ABCA1 Transporter on the cell surface and is responsible for active transport of cholesterol and lipids out of the cell into the HDL particle LDL Receptor Binds ApoB100 on LDL particles and facilitates the uptake of LDL particles SR1 Scavenger receptor, on liver cells and function in HDL particle uptake LPL Lipoprotein lipase On vascular epithelium; Cleaves TAGs into glycerol and FFAs to be stored in the adipose after being reformed into TAGs ApoE Apoprotein on chylomicrons and VLDL used for uptake by the liver *Transferred to chylomicrons and VLDL from HDL particles ApoCII Interacts with LPL (lipoprotein lipase) to activate the enzyme *Transferred to chylomicrons and VLDL from HDL particles CETP Cholesteryl ester transfer protein Transfers cholesteryl ester from HDL to VLDL and transfers TG from VLDL to HDL Chylomicrons transport... Dietary lipids and fat-soluble vitamins Where are chylomicrons synthesized? Intestinal epithelial cell --> released into circulation through lymph (chyle) *Microsomal transfer protein (MTP) is essential for the loading of ApoB48 on to the chylomicron Composition of a nascent chylomicron TAG, phospholipids, dietary cholesterol, ApoB48 Where are nascent chylomicrons secreted? -Into the thoracic duct and then into circulation -Nascent chylomicron interacts with HDL in circulation --> get a full complement of ApoE/ApoCII ApoCII on Chylomicrons and on VLDLs interact with... Lipoprotein lipase (LPL) -this hydrolyzes TAGs into FFAs -FFA are taken up by muscle (directly oxidized) or adipose (stored as TAGs) -insulin enhances the activity of LPL ApoE on chylomicron remnants... facilitates uptake by the liver SR-B1 receptor --> broken down into C, AA, and glycerol VLDL transports... fatty acids synthesized in the liver Where are VLDLs synthesized? in the hepatocyte and then released into circulation -microsomal transfer protein (MTP) essential for the loading of ApoB100 onto the VLDL (very similar to chylomicron synthesis) Composition of VLDL TAG, phospholipids, de novo cholesterol, ApoB100 -secreted directly into circulation *VLDLs interact with HDL in circulation, get a full complement of ApoE / ApoCII VLDL: ApoE on IDL facilitates uptake by the liver SR-B1 receptor --> broken down into C, AA, and glycerol LDL is a maturation product of... VLDL and retains ApoB100 LDL is largely filled with... cholesterol ester Extrahepatic tissues and the liver express... LDL receptor Uptake of LDL particles by peripheral tissues increases... intracellular concentration of cholesterol HDLs originate from... -the liver and intestine. -ApoA present on HDL particles