-
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
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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
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