Chapter 12 Flashcards
lipolysis
fatty acid degradation via B- oxidation
- TG cycle
- peroxisomes
- ketone bodies
fatty acid biosynthesis
- regulation
- membrane lipid metabolism
- isoprenoid metabolism
what are 3 sources of fatty acids in animals
- dietary triacylglycerois –>chylomicrons
- triacylglycerols stored in adipose tissue and released in response to hormones (glucagon, eprinephrine) –> fatty acids –>albumin
- triacylglycerols synthesized in the liver from carbohydrates and exported –> VLDL particles
“Digestion and aborption of triacylglycerols in small intestine”
fatty acids are important and efficient energy source for many cells
after triacylglycerol molecules are ingested, they are mixed with ____________
bile salts
digestion and absorption of triacylglycerols in the small intestine _____________pathway
exogenous
The ____________ is a mechanism that regulates the level of fatty acids available to the body for energy generation
triacylglycerol cycle
triglycerides
-triglycerides are a highly concentrated store of energy
- 9kcal/g vs 4 kcal/g of glycogen
- glycogen is also highly hydrated, 2 g H2O/g
Depending on the animals current metabolic needs, fatty acids may be:
- converted to triacylglycerols
- degraded to generate energy
- used for membrane synthesis
dietary triacylglycerols must be broken down before being absorbed by the intestines
_____, which act as detergents, are used to solubilize the triacylglycerols
bile salts
______________: hydrolyze the ester bond of the triacylglycerols while in the micelles
pancreatic lipases
in the intestinal mucosal cells, the fatty acids and monoacylglycerides are resynthesize into triacylglycerides and packed into ________________
chylomicrons
glycerol-3- phosphate or dihydroxyacetone phosphate reacts sequentially with three molecules of _________. Acyl-CoA molecules are fatty acid esters of CoASH
acyl CoA
_______________ is an abbreviated version of gluconeogeneis. This is where glycerol-3-phosphate is synthesized from substrates other than glucose or glycerol
glyceroneogenesis
when energy reserves are low, the body fat stores are mobilized in a process termed _____________.
- this occurs in adipose tissue during fasting, during vigorous exercise, and in response to stress
- fatty acid binding proteins are responsible for transporting the fatty acids into target organelles
lipolysis
lipid –>degration
triacylglyceride (use of lipase) —> glycerol –> fatty acids
lipolysis generates ____________ and _______
fatty acids and glycerol
Breakdown of triacylglycerols
-the glycerol is absorbed by the liver and converted to ______ intermediates
glycoytic
upon entering the cell cytoplasm, fatty acids are activated by attachment of _________
coenzyme A
transport into mitochondrial matrix via carnitine linkage
- acyl-CoA converted into acylcarnitine
- carrier protein transfers acylcarnitine into matrix
- acyl-CoA regenerated
- Carnitine recycled to intermembrane space
_________ is responsible for transporting acyl carnitine into the inner membrane of the mitochondria
acyl carnitine translocase
what are the four steps of fatty acid degradation that are repeated?
- OXIDATION of B carbon, catalyzed by ACYL COA DEHYDROGENASE
- HYDRATION of trans-2-enoyl CoA by ENOYL COA HYDRATASE
- OXIDATION of L-2-hydroxyacyl CoA by L-3-HYDROXYACYL DEHYDROGENASE
- CLEAVAGE of the 3-ketoacyl CoA by THIOLASE forms acytl-CoA and a fatty acid chain two carbons shorter
fatty acid degradation is also called ____________
B- oxidation
The reaction for one round of B-oxidation is?
where NADHx2.5
where FADHx1.5
make 31 NADH total
Makes 15 FADH2 total
takes 2 ATP to do
106 ATP total generated
processing of the products of the complete reaction by cellular respiration would generate 106 molecules of ATP
When does the generation of H2O occur?
it occurs when O2 is reduced in electron transport as well as formation of H2O in ATP synthesis reaction of oxidative phosphorylation
the degradation of MONOUNSATURATED fatty acid occurs with what enyzme?
cis-delta- enoyl CoA isomerase
POLYUNSATURATED fatty acid require isomerase and reductase. Which ones
Forexample Linoleoyl CoA uses: - cis-delta-enoyl coA isomerase -cis-delta-enoyl coA isomerase -2,4- dienoyl coA reductase
odd-chain fatty acids yield ______ in the final thiolysis step.
_______________ a biotin enzyme, adds a carbon to propionyl CoA to for methylmalonyl CoA
Succinyl CoA, a citric acid cycle component, is subsequently formed from methylmalonyl CoA by __________ a vitamen B12 requiring enzyme
propionyl CoA
propionyl carboxylase
methylmalonyl CoA mutase
alpha oxidation
degradation of branched - chain fatty acids, takes place in the _________-
peroxisomes
Ketone bodies are another fuel source derived from fats.
Ketone bodiy synthesis takes place in the liver
ketone bodies-acetoacetate, 3-hydroxybutrate, and acetone-are synthesized from acetyl CoA in liver mitochondria and secreted into the blood for used as fuel b some tissues such as heart muscle
the formation of ketone bodies involves what enzymes?
Enzymes:
- thiolase
- HMG CoA synthase
- HMG CoA lyase
- d-3-hydroxybutyrate dehydrogenase.
- Acetoacetate spontaneously decarboxylates to form acetone.
Ketone bodies
acetoacetate breaks down into what components?
D-3- hydroxy butyrate
acetone
The uilization of D-3-hydroxybutyrate and acetoacetate as a fuel uses what enzymes?
dehydrogenase
CoA transferase
Thiolase
To finally yield –> 2 acetyl CoA
Why can’t Acteyl CoA be used to generate glucose in citric acid cycle?
Pyruvate (3 chain carbon) is the end product of glycolsysis, pyruvate later get converted to a Acetyl CoA (2 chain carbon) through an enzyme called pyruvatedehydrogenase… If it was to generate glucose then the reaction would have to be able to happen in reverse. However this isn’t possible because there is no enzyme that does the opposite of pyruvatedehydrogenase.
Therefore animals cannot convert fatty acids into glucose
_________ results when insulin is absent
diabetic ketosis
fatty acid synthesis takes place in three stages:
- Transfer of acetyl CoA out of the mitochondria into the cytoplasm. Citrate is transported into the cytoplasm and cleaved into oxaloacetate and acetyl CoA.
2 .Activation of acetyl CoA to form malonyl CoA.
- Repetitive addition and reduction of two carbon units to synthesize C16 fatty acid. Synthesis occurs on an acyl carrier protein.
- citrate shuttle
________ is synthesized in the mitochondrial matrix, whereas fatty acids are synthesized in the ________
Acetyl-CoA units are shuttled out of the mitochondrial matrix as citrate
acetyl-CoA is synthesized in the mitochondrial matrix, whearas fatty acids are synthesized in the cytosol. Acetyl-CoA units are shuttled out of the mitochondrial matrix as citrate
The malate dehydrogenase and NADP^+ linked malate enzyme reactions of the citrate shuttle exchange ________ for ________
NADH for NADPH
- formation of malonyl coenzyme A
formation of ________ is the committed step in fatty acid synthesis
Acetyl-CoA carboxylase
malonly-CoA =commited step in fatty acid synthesis
Acetyl-CoA Carboxylase
-The carboxylation of acetyl-CoA to form malonyl-CoA is catalyzed by acetyl-CoA carboxylase, ACC
- ACC is found in most organisms
- Mammalian ACC contains two subunits each with a biotin cofactor
Regulation of fatty acid synthesis
- regulation of acetyl carboxylase
- GLOBAL
- +insulin
- -glucagon
- -epinphrine
- LOCAL
- citrate
- -palmitoyl CoA
- -AMPl
know what are positive and negative regulators
The remaining reactions of fatty acid synthetase takes place on the ___________
fatty acid synthetase multienzyme comlex (FAS)
____________, a complex of enzymes, catalyzes the formation of fatty acids.
Fatty acid synthesis occurs on the acyl carrier protein (ACP), a polypeptide linked to CoA. Intermediates are linked to the sulfhydryl group of the CoA attached to ACP.
__________ and _____________ attach substrates to the ACP.
fatty acid synthase
acetyl transacylase and malonyl transacyalse
the intermediates in fatty acid synthesis are covalently linked to the _________
acyl carrier protein (ACP)
Elongation
in _______ the enzyme that are involved in elongation are separate proteins;
In __________ the activities all reside on the same polypeptide
in bacteria
in higher organisms
fatty acid synthesis consists of _______,_______,__________-and_________-
condensation, reduction, dehydration, and reduction reactions
fatty acid synthesis
___________ catalyzes the condensation of acetyl ACP and malonyl ACP to form acetoacetyl ACP
the next three steps- reduction, dehydration, and another reduction-convert the keto group at carbon 3 to a methylene group (-CH2-) forming buyryl ACP
__________ is the source of reducing power
B ketoacyl synthase
NADPH
acyl-malonyl ACP condensing enzyme forms ___________
acetoacetyl-ACP
Elongation
-
- The NADPH is used instead of NADH and FADH2
- The D–enantiomer of Hydroxybutarate is formed instead of the L–enantiomer
the elongation cycle is repeated six more times, using malonl-coA each time to produce ____________
a thioesterase then cleaved the palmityl(C16) CoA from ACP
palmityl-ACP
multifunctional fatty acid synthase.
it is a functional enzyme that is composed of two identical chains
the enzyme consists of two distinct compartments
- The __________ compartment, which bind the acetyl and malonyl substrates and condenses them
- the _________ compartment, which carrier out the reduction and dehydration activities required for elongation
- selecting and condensing
2. modification
Elongation and unsaturated
Fatty acid synthase cannot generate fatty acids long than ________
longer fatty acids are synthesized by enzymes attached to the endoplasmic reticulum
these enzymes extend palmitate by adding two carbon units, using malonyl CoA as a substrate
C16 palmitate
Membrane bound enzymes generate unsaturated fatty acids
Enzymes bound to the endoplasmic reticulum introduce double bonds into saturated fatty acids
mammals lack the enzymes that introduce double bonds beyond carbon ___________
____ and ______ are essential fatty acids that must be obtained form the diet
carbon 9
linoleate and linolenate
Desaturation of stearoyl CoA
Desturase uses electron from ETS
-cytochrome bs
NADH is electron donor
General (may not be important)
Regulation of intracellular fatty acid metabolism
- both short- and long term regulatory processes are used
- in _________ regulation, enzymes are regulated by allosteric effectors, covalent modification (AMPK), and hormones
- _______ regulation is effected by alteration in gene expression
- in short-term regulation
- long term regulation
AMPK- Master regulator
5′-AMP-activated protein kinase is activated by an increase in _________ ratio
Switches anabolic pathways off and catabolic pathways on
Shifts metabolism from energy-consuming processes to energy-generating processes
- AMP/ATP
The liver is the primary site of cholesterol synthesis, although most tissues synthesize some cholesterol.
Cholesterol synthesis occurs in 4 stages.
- Formation of mevalonate from Acteyl-CoA
- Isopentyl pyrophosphate is synthesized from mevalonate.
- Six molecules of isopentyl pyrophosphate condense to form squalene.
- Squalene cyclizes and is converted into cholesterol.
Stage 1 occurs in the cytoplasm and stages 2 and 3 in the endoplasmic reticulum.
- Formation of HMG-CoA –> Mevalonate
HMG-CoA reductase is a target for some ______________
- Formation of Activated isoprene
pyrophosphate is a good ___________ in these nucleophillic substitution reactions
- formation of squalene
cardiovascular drugs
leaving group
cholesterol degrades into ??????/
lanosterol, terosterone, estradiol, cortisol, aldosterone, vitamam D, cell membrane, bile salts`
cholesterol homeostasis
–> intricate regulation through
- cholesterol
- LDL receptor activity
3, bile acid synthesis
regulation of cholesterol biosynthesis
insulin “high glucose”
glucagon “low glucose”
_____________are a class of drug that lowers serum cholesterol levels by inhibiting HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis
___________ also interfere with CoQ, a critical molecule in energy generation
statins
Molecules in meat may increase heart disease risk? describe this study and is it true?
Gut flora (of meat eaters) converts carnitine and choline into trimethylamine and enzymatic oxidation converts this to heart harming molecule TMAO (trimethylamine N-oxide) Gut microbes do not produce TMAO directly. They convert phosphatidylcholine (a common component of animal products such as meat and eggs) into a foul-smelling gas called trimethylamine; the liver then converts this gas into TMAO. L-carnitine passed right through the guts of long-term vegans and vegetarians, leaving their blood practically TMAO-free. When researchers examined volunteers’ stool, they found different groups of bacteria in people who did and didn’t eat meat.
