The role of gluconeogenesis in animal biology is to.... produce glucose to meet the body's needs during prolonged fasting/stress Gluconeogenesis occurs in the _________. liver In dogs, gluconeogenesis is the primary source of glucose after... 8+ hours of fasting Describe gluconeogenesis in cats. It is relatively constitutive because a prey-based diet is 70% protein and little glucose Ruminants have a ______ rate of gluconeogeneis because... high; little glucose is absorbed from their diet The target tissue of glucagon is ________, and it acts by inducing _________, which utilizes _________ for... liver; cAMP-dependent PKA; gluconeogensis; glucose synthesis from precursors The target tissue of epinephrine is _______, and it acts by inducing ________, which utilizes _______ for... adipose; lipolysis; cAMP-dependent PKA; glycerol release The target tissue of glucocorticoids is _________, and it acts by inducing _________, which utilizes _______ for... muscle; proteolysis; increased gene expression; amino acid release During prolonged fasting ______ are released from peripheral tissues (muscle) and are taken up by the liver to be converted to _____ by the _______. AAs; carbon skeletons; Kreb's cycle The Kreb's cycle intermediate __________ is transported out of the mitochondria and into the cytoplasm, where it is converted to _______ during _________. malate; glucose; gluconeogenesis _____________ is the rate-limiting, or slow, step in gluconeogenesis. Posphoenolpyruvate carboxykinase (PEPCK) PEPCK is regulated at the level of ______________ by _____________. transcription; glucagon-activate cAmp dependent PKA PEPKC is expressed almost exclusively in the ________. liver Ruminant feed contains ________ and __________, which are digested by.... complex starch and cellulose; microorganisms in the rumen Digestion of carbohydrates in the rumen results in ________. volatile fatty acids The major volatile fatty acids that result from ruminant digest are....; the major source of carbons for gluconeogenesis in the ruminant liver is ___________. acetate, propionate, and β-hydroxybutyrate; propionate The hexose-monophosphate shunt is only active when... there is a lot of glucose around The pentose phosphate pathway generates __________ for _______ synthesis. ribose; nucleic acid The pentose phosphate pathway synthesizes NADPH in the liver, adipose, and lactating mammaries for...; in the adrenals and testis for... fatty acid and cholesterol synthesis; steroid hormone synthesis 3 physiological roles of fat. major storage form of energy, regulatory molecules/bioactive lipids, structural roles Bioactive lipids play a major role in __________, a process in which... inflammation; the body's WBCs detect foreign invades to protect the body from infection To generate bioactive fatty acids, an external signal bind to a ________. GPR After the signal bunds to the receptor in the generation of bioactive lipids, PLA2 is activated, and it... cleaves fatty acids from the #2 position of membrane phospholipids Enzyme that cuts fatty acids off a glycerol backbone. lipase During generation of bioactive lipids, the fatty acids cleaved off by PLA2 is metabolized by __________ to __________ cyclooxygenase; PGG2 During the generation of bioactive lipids, PGG2s are further metabolized to... (3), which are bioactive lipids that... PGE2, TX2, and PGI2; recruit and activate WBCs to amplify the immune response NSAIDs block _______ to reduce _______. cyclooxygenase; inflammation Generic term for any 20 carbon fatty acid. Eicosanoid The functions of bioactive eicosanoids are best understood in... the immune response and inflammation Fatty acid are _______, ________ molecules. linear; unbranched ______ and _______ fatty acids are clinically significant. ω3 and ω6 Two significant groups of dietary PUFAs (polyunsaturated fatty acids) in animal heath: n-6 and n-3 _________ is an essential fatty acid in humans, rodents, canines, and cats. linoleic acid Cats require an extra essential fatty acid, _______. arachadonic acid Linoleic acid is metabolized to _______, which is further metabolized to bioactive __________. arachadonic acid; n-6 eicosanoids Linolenic acid (semi-essential) is metabolized to _______. n-3 eicosanoids Two sources of arachadonic acid: conversion of linoleic acid (primary) and direct consumption in animal products 2 sources of eicosapentanoic acid: conversion of linolenic acids from vegetable oils; direct consumption from fish products The term "2 series" refers to the 2 double bonds that remain after the conversion of ___________ to the ____________. arachadonic acid; bioactive eicosanoid The term "3 series" refers to the 3 double bonds that remain after the conversion of ___________ to the ______________. eicosapentanoic acid; bioactive eicosanoid ________ eicosanoids are biologically more active than ______ eicosanoids. n-6; n-3 Because of their increased number of double bonds, fish oils are susceptible to ________; when kept intact, they are useful in treating ________. oxidation; chronic allergies and dermatitis Cats lack ________ and therefore, they cannot... Δ6 desaturase; initiate the conversion of linoleic acid to arachadonic acid 3 functions of cholesterol. membrane structural component, steroid hormone precursor, bile sale precursor Statins block... cholesterol bosynthesis Most fat digestion is initiated in the ________ by the following two mechanisms... duodenum; emulsification by bile salts and hydrolysis by pancreatic lipase When fat digestion in the duodenum involves bile salts, the mechanism is... emulsification by bile salts to form micelles When fat digestion in the duodenum involves hydrolysis, the mechanism is... hydrolysis of the FA by pancreatic lipase to release monoglycerides and free fatty acids When fat digestion in the duodenum results in hydrolysis and formation of monoglycerides and free fatty acids, these components are... absorbed in the jejunum and reassembled into chylomicrons to re-enter circulation Cholesterol is the precursor of ________. bile acids Bile acid synthesis occurs in the _______, and bile acids function in ____________. liver; fat digestion The primary bile acids are... taurocholic acid and glycocholic acid In most species there is a mix of taurochoic and glycocholic acid as the bile acids, but in cats... all bile acids are taurocholic acid they are prone to taurine deficiency Bile acids are _________ and __________ during digestion in a process called ____________. reabsorbed and recycled; enterohepatic circulation All cat foods are supplemented with ________. taurine After dietary lipids are absorbed in the jejunum, the absorbed long chain fatty acids and monoglycerides are reassembled into ________ in the _________. triglycerides; jejunal mucosal cells The triglycerides that are reassembled in the jejunal mucosal cells are packaged into _________ by the enzyme ________. chylomicrons; microsomal triglyceride transfer protein (MTP) The drug Slentrol inhibits _______, and therefore blocking...... in order to treat...... Microsomal triglyceride transfer protein (MTP); packaging and transport of TGs in the jejunum mucosal cells; obesity in dogs by accumulation of lipids decreasing appetite Elevated serum lipids; relatively uncommon in animals, but usually secondary to diabetes or other endocrine problem. Hyperlipidemias Elevated serum chylomicrons; clinically significant problem in companion animals. hyperchylomicronemia (hypertriglyceridemia) The protein part of a lipid-protein complex. Apo-lipoprotein The major component of chylomicrons. triglyceride and cholesterol The four major proteins of chylomicrons. Apo A, Apo B48, Apo CII, Apo E The cholesterol exchange protein of chylomicrons. Apo A The transport/lipid packaging protein of chylomicrons. Apo B48 The lipoprotein lipase activator of chylomicrons. Apo CII The protein that binds to the liver receptor for chylomicrons. Apo E ___________ are rapidly cleared from the blood after a meal. chylomicrons During chylomicron metabolism, the chylomicron is secreted into the _______________ and them dumped into ____________. lymphatic system; systemic circulation During chylomicron metabolism, circulating chylomicrons become associated with the _____________ in __________, ___________, and __________ because these contain ____________. surface of endothelial cells; adipose, muscle, and heart tissue; lipoprotein lipase During chylomicron digestion, lipoprotein lipase is activated by interaction with _____________, which results in __________ of _________ within the chylomicron and uptake of _______ into the tissues. Apo CII; lipolysis; triglycerides; fatty acids During chylomicron digestion, as the chylomicron loses ___________, it shrinks and becomes a ____________. It also loses ________ and __________, but it retains _________ and __________. triglycerides; chylomicron remnant; Apo A and Apo CII; Apo E and Apo B48 During chylomicron digestion, the chylomicron remnant is taken up by the __________ by the chylomicron remnant receptor, which recognizes _________. liver; Apo E During chylomicron digestion, after the chylomicron remnant binds to the liver, it releases _________ and _________ into the liver cell. fatty acid and cholesterol The liver DOES NOT store ________ or ________; storage of these substances is a pathological disease known as ________. fatty acids or cholesterol; hepatic lipidosis Fatty acids that are deposited in the liver by chylomicron remnant are repackaged into _______ and sent ___________. very low density lipoproteins (VLDL); back into peripheral circulation The major component of VLDLs. triglyceride, cholesterol, cholesterol esters Most of the triglyceride in VLDLs is leftover from ___________. dietary TG from chylomicrons __________ are difficult to clear from circulation. LDLs VLDL is synthesized in the __________; VLDL transport _________ to the ___________. liver; TG; peripheral tissues During VLDL metabolism, __________ interacts with and activates _______ at the endothelial border of peripheral tissues. Apo CII; lipoprotein lipase During VLDL metabolism, lipoprotein lipase hydrolyzes the _______ from the ________ in the VLDL, which are then incorporated into _____________ for storage. fatty acids; TG; adipose tissue During VLDL metabolism, as VLDL lose ________ and _________, the VLDL becomes and Intermediate density lipoprotein (IDL). TG and Apo CII The 2 fates of IDLs. uptake into the liver via the LDL receptor (preferred); further breaker to form LDL LDL is composed mainly of _______ and ________. Apo B100 and cholesterol LDL binds inefficiently to _________, and therefore, it is... LDL receptor; difficult to clear from the blood HDL transports cholesterol from the _________ to the _______. peripheral tissues; liver HDL is synthesized in the... liver and small intestine HDL picks up _______ from the ________; this occurs when _______ activates the enzyme lecithin:cholesterol acetyltransferase, facilitating the transfer of ________ in the peripheral tissues to ______________ in the HDL particle. cholesterol; plasma membranes; Apo AI; cholesterol; cholesterol esters The cholesterol-containing HDL binds to a _________ on the surface of the ________, and ___________ are delivered. HDL receptor; liver cell; cholesterol esters HDL cholesterol delivered to the liver is converted to __________ or _____________. bile salts; repackaged into VLDL What is the main reason dogs and cats are protected from atherosclerosis? they maintain elevated HDL levels Persistently elevated HDL provides an effective mechanism to... continuously remove cholesterol from the peripheral tissues and reduce risk of atherosclerosis HDLs function _________; chylomicrons, VLDL, and LDL function in the __________. constitutively; fed state Fatty acid synthesis occurs when... energy intake exceeds energy expenditure (fed state) Fatty acid synthesis is driven by _________. insulin (which increases during fed state) Fatty acid synthesis takes place in which tissues? liver and adipose The major substrate for fatty acid synthesis in monogastrics.....; In ruminants... excess glucose; acetate What is the rate limiting step in fatty acid synthesis? acetyl-CoA carboxylase (ACC) Acetyl-CoA carboxylase (ACC) is regulated by... insulin and glucagon __________ turns on Acetyl-CoA carboxylase (ACC) by activating a protein that dephosphorylates and activates ACC in the fed state. Insulin ___________ activates AMP-dependent kinase, which phosphorylates and inactivates (inhibits) in the fasted state. Glucagon Acetyl-CoA carboxylase (ACC) converts _________ to ________, which contributes 2 carbon units to the ____________, a rxn catalyzed by __________. acetyl-CoA; malonyl-CoA; growing fatty acid chain; fatty acid synthase Excess glucose cannot be stored beyond.....; therefore, it is stored as... the limited storage of glycogen; fatty acids, which are stored as triglyceride The metabolism of dietary glucose provides carbons and ______, which is the source of H+'s for FAS. NADPH Oxaloacetate is metabolized to malate by ____________. malate dehydrogenase Malate is converted to pyruvate by _______, which generates _______. malic enzyme; NADPH The major source of NADPH for FAS under conditions of excess glucose intake is the ________. hexose monophosphate shunt Differences in energy metabolism for monogastrics and ruminants: Energy absorbed from diet- Energy source utilized by cells- Carbons for gluconeogenesis- Carbons for FAS- Source of NAADPH for FAS- Energy absorbed from diet- Glucose, FFA, MG (monogastric); acetate, propionate, butyrate (ruminant) Energy source utilized by cells- glucose, FFA (monogastric); acetate, butyrate (ruminant) Carbons for gluconeogenesis- AA, glycerol, lactate (monogastric); propionate (ruminant) Carbons for FAS- glucose (monogastric); acetate (ruminant) Source of NAADPH for FAS- HMS, malic enzyme (monogastric); isoitrate DH (ruminant) Potentially fatal condition in cats, associated with rapid uncontrolled weight loss. hepatic lipidosis Excessive mobilization of FFA from adipose tissue during a fast as a result of poorly managed weight loss lead to... excessive accumulation of fat in the liver Falling blood glucose levels activates... gluconeogenesis In response to a fast, __________ and ___________ occur simultaneously. gluconeogenesis; fatty acid oxidation __________ is the major hormone driving adipose tissue triglyceride lipolysis and fatty acid oxidation during a fast. epinephrine Epinephrine activates __________, which converts ATP to cAMP, which activates ___________. adenylate cyclase; PKA When Epi acts in the adipose tissue, PKA activates ______, which cleaves fatty acids from glycerol so they can be released into the blood and... .hormone-sensitive triacylglycerol; taken up and oxidized by the liver FFA are released from the ________ as a result of _________-induced lipolysis. adipose tissue; epinephrine FFA travel through blood bound to _________. albumin FFA taken up by the liver undergo ___________ in the mitochondria. β oxidation Enzyme that plays a major role in transport of "free" FA across the mitochondrial membrane for beta-oxidation. Carnitine Beta-oxidation in the mitochondria converts _______ to _______ and generates _______ and ________. Acyl-CoA to Acetyl-CoA; FADH and NADH FFA are taken up by the _________ during a fast, and they are converted to _______ by ________ in the cytoplasm. liver; fatty acyl-CoA; Acyl-CoA synthase (ACS) Acyl CoA passes through the outer mitochondrial membrane, but it is converted to ___________ by carnitine palmitoyl transferase I (CPT I) before it can be transported across the inner membrane. acylcarnitine Acylcarnitine is transported across the inner mitochondrial membrane by _________. carnitine acylcarnitine translocase (CAT) After acylcarnitine crosses the inner mitochondrial membrane, it is converted to ________ and _________ by __________. carnitine and Acyl-CoA; CPT II Acyl-CoA undergoes ____________ to form acetyl-CoA, which then enters the ________. beta-oxidation; Kreb's cycle Therapeutic weight-loss foods often contain high levels of ________ to help burn fat. L-carnitine What are the 3 stages of fasting and what occurs during them? 1. short term- basal FA oxidation 2. intermediate- increased FA oxidation, ketones in blood 3. long term- greatly increased FA oxidation, ketosis, hepatic lipiodsis Ketone synthesis begins after a period of... prolonged starvation (>24hrs) With ketone synthesis, excess _______ is produced and shunted to _________ in the ________. acetyl-CoA; ketone biosynthesis in the liver Ketones produced in the liver are released into the ___________ as...(3) Blood; acetone, acetoacetate, and beta-hydroxybuterate. During a prolonged fast, ketones are broken down to _________ via the _______ to generate _____. acetyl-CoA; Krebs cycle; ATP When, blood ketone levels become too high due to a protracted, lengthy, uncontrolled fast,ketones... cause acidosis, loss of electrolytes, dehydration, and coma. Hepatic lipidosis causes excessive mobilization of _______ into the _______, causing inadequate ___________ and increased _________ deposition. FFA into the liver; FA oxidation; TG Hepatic lipidosis can be linked to __________. gluconeogenesis Defective transport of _________ into the mitochondrion can result in accumulation of ________ in the liver, resulting in _________. acyl-CoA; fat(TG); hepatic lipidosis