Biochem 2: TEST 3!
1 gram of fat stores about.............. times as much energy as 1 gram of hydrated glycogen.
6.75
Where does the reducing power that fuels fatty acid synthesis come from?
8 NADPH is formed when 8 acetyl CoA are transferred from mitochondria to the cytoplasm for the synthesis of palmitate & additional NADPH molecules are from the Pentose Phosphate pathway.
How many acetyl CoA, ATP, and NADPH are required for C16 fatty acid synthesis?
8 acetyl CoA 7 ATP 14 NADPH
What is the structure of a fatty acid?
A long hydrocarbon chain and a terminal carboxylate group
Both fatty acid and cholesterol synthesis stops at low...........
ATP
What drives the formation of the thioester linkage between the carboxyl group of a fatty acid and the sulfhydryl group of coenzyme A?
ATP
During starvation, oxaloacetate is used to form glucose. acetyl CoA is diverted to form acetoacetyl CoA. .................................are often referred to as ketone bodies. 2 acetyl CoA -> acetoacetyl CoA -> 3-hydroxy-3-methylglutaryl CoA -> acetoacetate -> EITHER acetone OR d-3-hydroxybutyrate.
Acetoacetate, D-3-hydroxybutyrate, and acetone
What are the effects of consuming a diet made up mostly of fats?
Acetone concentration increases Acetyl-CoA concentration increases Oxaloacetate concentration decreases
...........................controls fatty acid metabolism.
Acetyl CoA Carboxylase
What does each round of fatty acid oxidation produces?
Acetyl CoA, NADH, and FADH2
Cholesterol modulates membrane fluidity and is the precursor for steroid hormones. All 27 carbons are derived from................... moieties.
Acetyl coA
What are the different pathways to synthesize phospholipids?
Activated diacylglycerol or activated alcohols. - EITHER activated diacylglycerol reacts with alcohol groups (such as inositol or phosphatidylglycerol) - OR Alcohols are activated in two steps and then react with diacylglycerol (forming things such as phosphatidylethanolamine or phosphatidylcholine)
What are the enzymes that participate in the β-oxidation pathway
Acyl CoA dehydrogenase Enoyl CoA hydratase L-3-hydroxyacyl CoA dehydrogenase β-ketothiolase
What enzyme catalyzes this activation rxn?
Acyl CoA synthetase
Acyl carnitine is transported from the mitochondrial inner space to the mitochondrial matrix by................ And the acyl group is transferred back to............ on the matrix side.
Acyl carnitine translocate coenzyme A
...................... are cells that specialize in the storage of triacylglcerols.
Adipocytes
Where do the carbon atoms in cholesterol come from?
All 27 carbons are derived from acetyl CoA moieties.
What is ACP?
An acyl carrier protein. It is a single polypeptide chain of 77 residues, and it is regarded as a giant prosthetic group.
What are bile salts?
Bile salts are polar derivatives of cholesterol and are detergents for polar and non-polar groups. Synthesized in the liver, concentrated in gall bladder, and released into small intestine. They are modified by both liver and gut bacteria to give a number of related derivatives.
What do bile salts do?
Bile salts work by solubilizing dietary lipids in the intestines. Lipid solubilization exposes more of the lipid surface to lipases and thus enables the breakdown of triacylglycerides; lipids are also more readily absorbed by the intestine. Major breakdown products of cholesterol.
What carries fatty acids to needy tissues?
Blood albumin
How fatty acids are transported in the blood?
Blood albumin is a fatty acid carrier that brings them to needy tissues.
Where are both the enzymes involved in making phosphatidate into triacylglycerol (phosphatidic acid phosphatase & Diglyceride acyltransferase) located?
Both are associated in a triacylglycerol synthetase complex that is bound to the ER membrane.
How phosphatidate is activated?
By phosphatidate cytidylyltransferase (also called CDP- diacylglycerol synthase) This enzyme catalyzes the synthesis of CDP-diacylglycerol from cytidine triphosphate and phosphatidate.
What is the final product of regular synthesis of fatty acid?
C16 palmitic acid
A variety of unsaturated fatty acids can be made by combination of elongation and desaturation. Additional double bonds can also be inserted. Mammals lack an enzyme to introduce double bond into fatty acids (linoleate or linolenate) beyond.......... and so they must come from your diet.
C9
Mammals lack enzyme to introduce double bonds into fatty acids (linoleate or linolenate) beyond........ and so they must come from your diet.
C9
What are the signal molecules that regulate (enhance or inhibit) the activity of PAP?
CDP-diacylglycerol, phosphatidylinositol, and cardiolipin enhance PAP activity. Sphingosine and dihydrosphingosine inhibit PAP.
How is Propionyl CoA carboxylated?
Carboxyl is activated by ATP, and Propionyl CoA carboxylase catalyzes the carboxylation.
............................is the precursor of sphingolipids.
Ceramide (it is a lipid consisting of a fatty acid chain attached to the amino group of a sphingosine backbone)
....................modulates membrane fluidity and is the precursor for steroid hormones.
Cholesterol
Where does cholesterol come from?
Cholesterol can be de novo synthesized or obtained from diet. (Biosynthesis rate varies greatly and are highly responsive to cellular levels of cholesterol)
Which of these is for the method of phosphatidylcholine synthesis involving choline, and which is for the method involving phosphatidylethanolamine? -predominate pathways in mammalian -Pathway requires phosphorylation by CTP -Pathway involves 1,2-diacylglycerol -possible pathway in mamaliam liver -pathway requires S-adenosylmethionine as the source of methyl groups. -pathway involves a series of methylations *
Choline: -predominate pathways in mammalian -Pathway requires phosphorylation by CTP -Pathway involves 1,2-diacylglycerol Phosphatidylethanolamine: -possible pathway in mamaliam liver -pathway requires S-adenosylmethionine as the source of methyl groups. -pathway involves a series of methylations
What are the different lipoproteins?
Chylomicron, VLDL, IDL, LDL, HDL. (lowest density -> highest density) VLDLis very low density lipoprotein, IDL is intermediate density lipoprotein.
........................: transports dietary triacylglycerols (triglyceride) to tissues. ........................: transports endogenous triacylglycerols (triglycerides) from liver to tissues. ........................: transports cholesterol from liver to tissues. ........................: transports cholesterol from tissues to liver. *
Chylomicrons VLDL LDL HDL
Fatty acids are synthesized in the cytoplasm, whereas acetyl CoA is formed from pyruvate in mitochondria. How are acetyl groups transported from mitochondrion to cytoplasm?
Citrate carries acetyl groups from mitochondria to the cytoplasm, at the expense of one molecule of ATP. Citrate is formed in the mito matrix by the condensation of acetyl CoA with oxaloacetate. Once in the cytoplasms, it is cleaved by ATP-citrate lyase.
How are odd-chain fatty acids degraded, and what is the unique product and how it is processed? (Remember, odd chain fatty acids are different than unsaturated fatty acids with an odd number of double bonds).
Degradation leads to Propionyl CoA and acetyl CoA (rather than 2 molecules of acetyl CoA) being produced. Propionyl CoA needs to be converted into succinyl CoA so it can enter the citric acid cycle.
What is the enzyme that synthesize fatty acid?
Fatty acid synthase, which is a complex of enzymes.
How do the acyl carriers in degradation and synthesis differ?
Fatty acid synthesis uses beta-ketoacyl synthase.
What are the major phospholipids that are synthesized?
From activated alcohol: phosphatidylcholine is the most common, then phosphatidylethanolamine. From activated diacylglycerol: diphosphatidylglycerol (cardiolipid) phosphatidylinisotol Phosphatidylserine
What hormones regulate the hydrolysis of triacylglycerols by inducing lipolysis?
Glucagon and epinephrine
What happens to glycerol?
Glycerol is absorbed by the liver and phosphorylated. It is oxidized to dihydroxyacetone phosphate, which is isomerized to glyceraldehyde 3-phosphate. Then it can be used to generate energy (glycolysis, which makes pyruvate) or stored as glucose (gluconeogenesis).
Note that molecular oxygen gets reduced to 2.................molecules. Two electrons come from NADH and two more from the single bond of the fatty acyl substrate.
H2O
........................picks up cholesterol from membrane turn-over cells, and also dying cells, and brings it to the liver for excretion.
HDL
So,................. mevalonate means reduced translation of HMG CoA reductase mRNA.
HIGH
...................................is the irreversible control point in cholesterol synthesis.
HMG-CoA reductase
Mevalonate formation is catalyzed by............................. on the ER membrane.
HMG-CoA reductase
Why does the liver have acetoacetate available to supply the other organs? Shouldn't acetoacetate be processed in the liver by these enzymes too?
High concentrations of acetoacetate in the blood regulate the rate of lipolysis in adipose tissue.
PAP activity also determines which phospholipids will be produced. When PAP activity is high, what is produced? When PAP is low, what happens?
High: triacyl glycerol, phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine. Low: more phosphatidate is formed and is used as a precursor for different phospholipids, such as phosphatidylinositol and cardiolipin. Phosphatide also regulates the growth of ER and nuclear membranes, and turns on genes for phospholipid synthesis.
Why is LDL critical in cholesterol metabolism?
In general, cells and tissues outside the liver (non-hepatic) obtain cholesterol from the plasma rather than synthesizing it de novo. So, their primary source of cholesterol is from LDL thru receptor mediated endocytosis.
Where are phospholipids and other membrane lipids synthesized?
In the ER and the golgi apparatus.
Acetyl CoA is also controlled by hormones glucagon, epinephrine, and insulin. Which hormones stimulate fatty acid synthesis and which inhibit it?
Insulin stimulates fatty acid synthesis by stimulating the carboxylase, whereas glucagon and epinephrine have the opposite effects.
How cholesterol synthesis is regulated?
It depends on the cellular level of cholesterol, so primarily regulated by the levels and activities of 3- hydroxy-3-methylglutary CoA reductase (HMG-coA reductase).
Why is phosphatidate synthesis a critical step for lipid synthesis?
It is a common intermediate in the synthesis of phospholipids and triacylglycerols. The synthesis of phosphatidate is the first step in their synthesis.
What is the structure of the mammalian synthase complex?
It is a mega enzyme that is linked through a large polypeptide chain. The enzyme is a dimer of 270-kd subunits. Each chain contains all of the active sites required for activity, as well as an acyl carrier protein tethered to the complex. But, the monomers are not active, and need to be in a dimer. It has these components: DH (dehydratase) ER (enoyl reductase) KR (ketoreductase) TE (thioesterase) KS (ketosynthase) MAT (malonyl-acetyl-transferase)
Triglycerols are broken down into glycerols and fatty acids. What happens to the glycerols?
It is absorbed by the liver and can be used to generate energy through glycolysis or it can go through gluconeogenesis to be stored as glucose.
How do oxaloacetate and acetyl CoA condense to form citrate?
It is catalyzed by citrate synthase. There is an Aldol condensation followed by hydrolysis of the thioester bond.
Why is the formation of malonyl CoA critical?
It is the first step and committed step in fatty acid synthesis.
Excess cholesterol is in the form of...................... which is a major carrier of cholesterol in blood. It transports cholesterol to peripheral tissues and regulate de novo synthesis of cholesterol there.
LDL (bad!! taking cholesterol to other tissues, not a good thing)
What are good and bad cholesterols?
LDL (bad) HDL (good)
What problem is associated with absorbing dietary lipids?
Lipids are not soluble in water. (the solution is to wrap lipids in a soluble container, as a micelle!)
How are cholesterol and triacylglycerols transported in the body?
Lipoprotein particles transport cholesterol and triacylglycerols (TAGs) throughout the body.
What parts of the body make cholesterol?
Liver is the major site, while intestine can make it too
How and where is further elongation of fatty acids done?
Longer fatty acids are formed by elongation rxns by enzymes on the cytoplasmic face of the endoplasmic reticulum membrane. These rxns add 2C units sequentially to the carboxyl ends of both saturated and unsaturated fatty acyl CoA substrates.
What causes Infant respiratory distress syndrome (IRDS)?
Lungs normally secrete dipalmitoyl phosphatidylcholine (DPPC) to prevent alveoli collapse. In IRDS patients, underdeveloped lungs cannot produce enough DPPC. When air is exhaled, the alveoli contract and can collapse.
Mammalian fatty acid synthase is a mega-enzyme of a 270 kd dimer. This is how it works: - An elongation cycle begins when.................. moves an acetyl unit from CoA to the ACP. - ................ accepts the acetyl unit (notice the thioester bond between the enzyme active site and the acetyl unit); -the vacant ACP is reloaded by MAT with a........................... -malonyl ACP accesses the KS active site and what occurs? -the selecting and condensing process ends up with the beta-ketoacyl product attached to ACP.
MAT (malonyl-acetyl transferase) KS (Ketosynthase) malonyl moiety. condensation and CO2 release occurs.
What tissues use ketone bodies and under what conditions?
Major site of production is in the liver. They are transferred to tissues such as the heart and kidney. Heart muscle and the renal cortex use acetoacetate in preference to glucose. And, in prolonged starvation, 75 % of the fuel needs of the brain are met by ketone bodies.
To make longer fatty acids, .........................is the 2 carbon donor, and condensation is driven by....................
Malonyl CoA the decarboxylation of malonyl CoA.
What are the 2 different mechanisms in which Acetyl CoA Carboxylase controls fatty acid metabolism?
Mechanism 1: AMP-dependent protein kinase (AMPK) senses AMP levels and phosphorylates acetyl CoA carboxylase which inactivates it. Negatively regulated by ATP. Thus, when the energy charge is low, its not a good time to start making fatty acids! Mechanism 2: Citrate allosterically controls the oligomerization of acetyl CoA carboxylase which stimulates activity (even in the presence of phosphorylation). Citrate levels are high when acetyl CoA and ATP are high.
Acetyl CoA Carboxylase controls fatty acid metabolism. What are the 2 mechanisms?
Mechanism 1: AMP-dependent protein kinase (AMPK) senses AMP levels and phosphorylates acetyl CoA carboxylase which inactivates it. So it is negatively regulated by ATP. Thus, when the energy charge is low, its not a good time to start making fatty acids! Mechanism 2: Citrate allosterically controls the oligomerization of acetyl CoA carboxylase which stimulates activity (even in the presence of phosphorylation). Citrate levels are high when acetyl CoA and ATP are high.
...................... synthesis is the committed step in cholesterol synthesis.
Mevalonate
How does monooxygenase work?
Monooxygenases, or mixed function oxidase, transfer one oxygen atom to the substrate (making a hydroxyl group), and reduce the other oxygen atom to water.
The reaction involving the enzyme L-3-hydroxyacyl CoA dehydrogenase also uses......................
NAD+
cytochrome P450 requires............. and............
NADPH and O2
What is the enzyme that determines the ratio between phospholipids and triacylglycerol?
PAP.
The phospholipid and triacylglycerol pathways diverge at what?
Phosphatidate
What is the key regulatory step in lipid metabolism?
Phosphatidic acid phosphatase (PAP) (which works in concert with diacylglycerol kinase, DGK)
............................... converts phosphatidate (phosphatidic acid) to diacylglycerol (DAG). In the reverse reaction, which is considered a salvage pathway to get more phosphatidate, ....................... converts DAG to phosphatidate. *
Phosphatidic acid phosphatase (PAP, also called lipin) Diacylglycerol kinase (DGK)
.......................... is the major phospholipid in the inner leaflet of cell membrane.
Phosphatidylethanolamine
How is phosphatidylserine formed?
Phosphatidylserine is formed by reacting phospholipid with serine from phosphatidylethanolamine or phosphatidylcholine, in a process called alcohol exchange.
How phospholipids are made?
Phospholipid synthesis requires the activation of phosphatidate in the ER and Golgi to give diacylglycerol. Then there is a combination of diacylglycerol with an alcohol. One of the components must be activated. In this case, either the diacylglycerol OR the alcohol may be activated, depending on the source of the reactants.
Phosphatidate is a precursor in the synthesis of some lipids. Which lipids are these? *
Phospholipids and triacylglylcerols
How does PKA activate hormone-sensitive (HS) lipase?
Phosphorylation
What is the common precursor of eicosanoid hormones?
Polyunsaturated fatty acids such as arachidonate.
..................... is the precursor for most steroid hormones. Removing the 6 carbon tail from cholesterol forms this.
Pregnenolone
Processing of odd-chain fatty acids yields...................... which gets converted into.......................
Propionyl CoA Succinyl CoA
stage 1 of fatty acid processing involves breaking down triacylglycerols into fatty acids in adipose tissues. ........................activates Perilipin, and hormone-sensitive lipase, to initiate lypolysis.
Protein Kinase A (PKA)
Like acetyl CoA carboxylase, pyruvate carboxylase utilizes the covalently attached prosthetic group biotin and ATP to promote product formation. What is this rxn?
Pyruvate -> oxaloacetate
What are the roles of sphingolipids?
Serve as secondary messengers (regulate cell growth and death) and help form lipid rafts.
The tertiary alcohol then does what?
Spontaneously decarboxylates to 3-isopentenyl pyrophosphate.
What are the stages of fatty acid processing?
Stage 1: The lipids are mobilized. This is done by breaking down triacylglycerols into fatty acids and glycerol in adipose tissues, then transporting them to energy requiring tissues. Stage 2: Fatty acids are activated by acyl CoA synthetase and transported into mitochondria for degradation. Stage 3: Fatty acids are then broken down into acetyl CoA (which is a substrate of the citric acid cycle)
What are steroid hormones?
Steroid hormones coordinate organ functions in higher organisms. Steroid hormones diffuse across membranes and bind to soluble receptors. Receptors dimerize, enter the nucleus and perform signal transduction as transcription factors.
How gangliosides are synthesized?
Sugars are added step-by-step to ceramide, in reactions involving activated sugars with UDP (sugar) or CMP (sialic acids).
Where does glycerol 3-phosphate come from?
The reduction of dihydroxyacetone phosphate (DHAP) synthesized by the gluconeogenic pathway. Glycerol 3-phosphate can also be produced by phosphorylation of Glycerol.
How are unsaturated fatty acids degraded?
The same way as for saturated fatty acids, except for an isomerase and a reductase are needed. Fatty acids with an odd number of double bonds are handled by the isomerase, and even number of double bonds are handled by the reductase AND the isomerase.
How does the LDL receptor work?
The synthesis/expression of the LDL receptor is subject to feedback regulation by SREBP. When cholesterol is abundant, new LDL receptors are not synthesized, and so the uptake of additional cholesterol from plasma LDL is blocked.
How is the HMG CoA reductase regulated by transcription?
The transcription factor known as the sterol regulatory element binding protein (SREBP) binds to a short DNA sequence called the sterol regulatory element (SRE) on the 5' side of the reductase gene. It binds to SRE when cholesterol levels are LOW and ENHANCES transcription.
How are fatty acids activated for degradation? Where does this take place?
They are activated through the formation of a thioester linkage to coenzyme A before they enter the mitochondrial matrix. This takes place on the outer mito membrane.
How triacylglycerols are hydrolysed in adipose tissues?
They are hydrolyzed by hormonally controlled lipases! Hormones trigger 7 TM receptors that activate adenylate cyclase. This increases the levels of cAMP which will then signal protein kinase A (PKA), which will then phosphorylate 2 key proteins: perilipin and hormone-sensitive lipase. Once phosphorylated perilipin does 2 things: - It restructures the fat droplet so that the triacylglycerols are more accessible to mobilization. - It triggers the release of a coactivator for the adipose triglyceride lipase (ATGL).
cholesterol has 27 carbons, and we used 18 Acetyl CoAs (which have 36 carbons). What happen to the carbons in acetyl CoA during cholesterol synthesis?
They are lost as CO2.
How and when are ketone bodies produced?
They are produced when fat breakdown predominates. Acetyl CoA must combine with oxaloacetate to gain entry to the citric acid cycle. In fasting or diabetes, oxaloacetate is consumed to form glucose by the gluconeogenic pathway and hence is unavailable for condensation with acetyl CoA. Under these conditions, acetyl CoA is diverted to the formation of acetoacetate and D-3- hydroxybutyrate, which are known as ketone bodies.
Why do fatty acids store more energy than glycogen?
They are reduced and anhydrous! (1) fatty acids are much more reduced than sugars (2) triacylglycerols are nonpolar and anhydrous, whereas sugars are polar and therefore hydrated. This results in a huge increase in weight of sugar through water.
How are chylomicrons transported to target cells?
They are released into the lymph system and then into the blood. Once in the blood they bind to membrane-bound lipases on adipose tissue and muscle, are broken down into fatty acids and monoacyl glycerol, transported into the tissues, and re-synthesized into triacylglycerol and stored.
What are the major tissues or cells that store the fatty acids and in what form?
They are stored as triacylglycerols, which are uncharged esters of fatty acids with glycerol. Triacylglycerols are stored in adipose tissue, specifically in the cytoplasm of adipocytes.
What are the bile salts, which organ produces them and what function do they do?
They are synthesized by the liver and secreted by the gall bladder. They are ampiphathic molecules that facilitate lipid digestion. An example of a bile salt is glycocholate
How and where are unsaturated fatty acids synthesized?
This is done with a three protein system in the endoplasmic reticulum. These proteins are NADH-cytochrom b5 reductase, cytochrome b5, and desaturate. In this process molecular oxygen gets reduced to 2 H20 molecules; two electrons come from NADH and two more from the single bond of the fatty acyl substrate.
How are fatty acids degraded?
Through fatty acid oxidation
What is the difference between phospholipids and sphingolipids?
Unlike phospholipids, sphingosine serves as the backbone instead of glycerol.
How do you name the carbons and rings in cholesterol?
When the hydroxyl group is above the plane (on a wedge) its beta, and when its below the plane (on a dash) its alpha.
What are the other organelles that oxidize fatty acids?
While most fatty acid oxidation takes place in mitochondria, some can occur in peroxisomes. This is thought to promote the shortening of long fatty acid chains into octanoyl CoA which makes them better substrates of β-oxidation in the mitochondria.
In humans that cannot produce insulin, high blood levels of ketone bodies, referred to as ketosis, can occur and is life-threatening! Why?
Without insulin, the liver cannot take up glucose and subsequently produce oxaloacetate. Ketone bodies will form, and then the blood pH will drop causing acidosis, and then they will go into a coma and can die.
What are statins?
a class of Inhibitors for HMG-CoA reductase, so inhibitors of cholesterol synthesis.
In cerebroside, the substituent on the hydroxyl group of ceramide is what?
a glucose or galactose.
The 5'-deoxyadenosyl radical is very reactive: it abstracts a hydrogen atom from the substrate to form a substrate radical. The substrate radical then spontaneously rearranges. So, the role of coenzyme B12 is to serve as:
a source of free radicals for the abstraction of hydrogen atoms.
high concentrations of.......................... in the blood regulate the rate of lipolysis in adipose tissue.
acetoacetate
What are ketone bodies?
acetoacetate and D-3- hydroxybutyrate
Ketone bodies are formed from............... when fat breakdown predominates (when there is a lack of carbohydrates).
acetyl CoA
The first and committed step in fatty acid synthesis is catalyzed by the enzyme............................ This rxn is: This enzyme uses what else to do this?
acetyl CoA carboxylase Acetyl CoA -> malonyl CoA covalently attached biotin prosthetic group, and ATP
Fatty acid synthesis involves the condensation of two activated groups:
acetyl coA and malonyl coA.
What are the building blocks for fatty acid synthesis?
acetyl groups derived from acetyl CoA, which will be carboxylated into malonyl CoA.
In stage 2 of fatty acid processing, fatty acid activation is catalyzed by.....................
acyl CoA synthetase
Intermediates in fatty acid synthesis are attached to an................... protein.
acyl carrier
Gangliosides are complex sphingolipids with acidic sugar substituents (sialic acids). They are very diverse, with more than 60 currently known. Gangliosides serve as.......................... sites for external proteins.
binding
Processing of a polyunsaturated fatty acid requires the action of........................
both an isomerase and a reductase. Consider the fatty acid linoleate (C18): it contains two double bonds (cis-Δ9 and cis-Δ12). The first double bond is processed with isomerase, but then the molecule (2,4-Dienoyl CoA) still contains the second bond and is not a substrate for the next enzyme in the β-oxidation pathway. The reductase reduces this substrate to trans-Δ3-Enoyl CoA, and now the isomerase can take over and then the β -oxidation pathway can occur.
Malonyl CoA (the product of acetyl CoA carboxylase) inhibits................................, preventing....................................
carnitine acyltransferase I the entry of fatty acids into the mitochondrial matrix to be degraded
Malonyl CoA (the product of acetyl CoA carboxylase) inhibits.................................., preventing...............................
carnitine acyltransferase I the entry of fatty acids into the mitochondrial matrix to be degraded.
.................is used as both a membrane component, and as a precursor of many signal molecules such as the steroid hormones progesterone, testosterone, estrogen, and cortisol.
cholesterol
Triacylglycerols are resynthesized from fatty acids and monoacylglycerols and then packaged into stable lipoprotein transport particles called............................ that transport them and also fat soluble vitamins and cholesterol.
chylomicrons.
How acetyl CoA Carboxylase activity responds to both the presence of...................... and ........................
citrate and phosphorylation.
Basic steps of fatty acid synthesis:
condensation reduction dehydration reduction
what are the steps in fatty acid synthesis?
condensation -> reduction -> dehydration -> reduction - The individual units are assembled (in the example we learned its an an acetyl unit and a malonyl unit combining) - Carbonyl group is reduced to a methylene group through a reduction, a dehydration, and another reduction . (butyryl CoA is the product, and it condenses with another activated malonyl group to repeat the process until a C16 or shorter fatty acid is synthesized)
the hydroxylation of steroids is catalyzed by................... (which catalyzes a monooxygenase reaction)
cytochrome P450
Acetoacetyl CoA and acetyl CoA reacts to form HMG-CoA (ketone bodies). HMG-CoA becomes ketone bodies in the mitochondria & mevalonate in the...................
cytoplasm
Phosphorylation.................... activity of HMG-coA reductase.
decreases
What disease(s) is associated with high blood ketone bodies and what problems may develop?
diabetes. Without insulin, the liver cannot take up glucose and subsequently produce oxaloacetate.
What are unique properties of fatty acids as the primary fuel?
during rest or moderate exercise, fatty acids are humans primary source of energy.
A three protein..................... system introduces double bonds in the fatty acids.
endoplasmic reticulum
The synthesis of Phosphatidylcholine has two different pathways. Most commonly, Choline comes in through diet, and is activated in a series of reactions analogous to those in the activation of................. The other pathway can only occur in the............... because it contains the enzyme....................., which synthesizes phosphatidylcholine from........................... when dietary choline is insufficient. *
ethanolamine liver phosphatidylethanolamine methyltransferase phosphatidylethanolamine
So, the β-oxidation pathway accomplishes the complete degradation of saturated fatty acids with an........... number of carbon atoms.
even (fatty acids that contain double bonds or odd numbers of carbon atoms will be processed differently, as explained in the next slides)
In higher organisms, ................................ is a mega-enzyme that contains multiple enzymatic functions in one long polypeptide chain. The growing fatty acid chain is elongated by the sequential addition of................. derived from...............
fatty acid synthase acetyl groups acetyl CoA
How are steroid hormones synthesized?
from cholesterol
What is the enzyme catalyzing this first step and where does it happen?
glycerol phosphate acyltransferase. Occurs in the ER and the outer mitochondrial membrane. (Can also be synthesized from diacylglycerol by the salvation pathway catalyzed by diacylglycerol kinase)
The addition of 2 fatty acids to.................... yields phosphatidate.
glycerol-3-phosphate
In the active site of methylmalonyl CoA, a............... binds to cobalt in place of benzimidazole to facilitate the cleavage of the cobalt-carbon bond and abstration of hydrogen from the substrate.
histidine
Acetyl CoA is also controlled by.................................
hormones glucagon, epinephrine, and insulin. (Insulin stimulates fatty acid synthesis by stimulating the carboxylase, whereas glucagon and epinephrine have the opposite effects)
Where is HMG-CoA reductase located?
in the ER membrane.
While fatty acid synthesis is the reversal of the degradative pathway in terms of chemical reactions, the synthesis and degradation pathways are different mechanistically. Synthesis takes place where?
in the cytoplasm (recall that degradation took place in the mitochondrial matrix).
The major site of the production of ketone bodies is where?
in the liver.
diphosphatidylglycerol (cardiolipid) is exclusively localized in the........................ membranes. It is critical for the organization of oxidative phosphorylation (cytochrome oxidase).
inner mito
So, cobalamin (Vitamin B12) containing enzymes catalyze what?
intra-molecular rearrangements.
Processing of a fatty acid with an odd-numbered double bond require the action of an................
isomerase. Consider the fatty acid palmitoleate, a C16 unsaturated fatty acid with a double bond between C-9 and C-10. Fatty acid degradation occurs normally until the formation of cis-Δ3-Enoyl CoA, which is not a substrate for acyl CoA dehydrogenase. This is resolved by the action of a new reaction that shifts the position and configuration of the cis-Δ3 double bond. The enzyme, cis-Δ3-Enoyl CoA isomerase, coverts this double bond into a trans-Δ2 double bond. Now the substrate is ready for the reactions typical of saturated fatty acid oxidation.
What is the key building block for cholesterol synthesis?
isopentenyl pyrophosphate (the activated form of isoprene)
So, in stage one, Acetoacetyl CoA and acetyl CoA reacts to form HMG-CoA, and then HMG-CoA reductase makes it into mevalonate in the cytoplasm. Mevalonate is converted into 3-isopentyl pyrophosphate in 3 consecutive reactions involving ATP. Then, the release of CO2 yields........................
isopentyl pyrophosphate
Why are they called ketone bodies?
ketone bodies are simply another water-soluble, transportable fuel source of acetyl units.
What is the consequence of high blood levels of ketone bodies?
ketosis can occur which is life-threatening.
How are fatty acids absorbed?
lipids are ingested in the form of triacylglycerols and must be degraded to fatty acids for absorption across the intestinal epithelium. To do this, they are solubilized in micelles composed of bile salts. The ester bond of the lipids are oriented towards the surface of the micelle, allowing access to the lipases. Lipases degrade triacylglycerols into fatty acids and monoacylglycerol. These products are carried in micelles to the epithelium and are transported.
Cholesterol, a vital component of membranes and precursor to signaling molecules (steroid hormones), must also be transported. Cells cannot degrade cholesterol. Thus, excess cholesterols and steroids must be taken to the........... and excreted.
liver
The......... is the primary site of triacylglycerol synthesis. From there, triacylglycerols are transported to the muscles for energy conversion or to the adipose cells for storage.
liver
Gangliosides are normally degraded one sugar at a time inside................... Tay-Sachs is caused by failure of ganglioside degradation. Lipids accumulate and neurons become swollen with abnormally large.................. The kids die by age 3 :(
lysosomes lysosomes
In the mechanism of beta-ketoacyl synthase, ........................ is the donor.
malonyl ACP
The activated donor of two carbon unit in elongation is........................ and the reaction is driven by release of.......... The reductant in fatty acid synthesis is.....................
malonyl ACP CO2 NADPH (recall that the oxidants in fatty acid degradation are NAD+ and FAD+).
In yeast, phosphatidylcholine is derived from phosphatidylethanolamine via a series of............... *
methylations
the L isomer of Methylmalonyl CoA is converted to Succinyl CoA by......................., which catalyzes an intramolecular rearrangment using a....................... coenzyme.
methylmalonyl CoA mutase cobalamin
Remember, once HMG-CoA is formed, it can either become ketone bodies in the............... or mevalonate in the.....................
mitochondria cytoplasm
Where are fatty acids oxidized?
mitochondrial matrix
Continued: - The β-ketoacyl product remains attached to ACP and next visits the.................... compartment of the enzyme - First, the β-keto group is reduced to............., ...................., and then reduced to yield the saturated acyl product (which is still attached to the ACP). - The reduced product then gets transferred to.............. and ACP accepts another malonyl unit - The process is repeated until the.................. releases the final C16 palmitic acid product.
modification -OH dehydrated KS (ketosynthase) TE (thioesterase)
The loss of PAP function prevents normal adipose tissue development. Excess PAP activity results in.................
obesity.
Fatty acids are activated where? Then, they are transported into the matrix by conjugation to.................
on the outer mitochondrial membrane Carnitine (This is catalyzed by the enzyme carnitine acyltransferase I, also called carnitine palmitoyl transferase I & CPTI, which is bound to the mitochondrial outer membrane.)
Recall that the citric acid cycle depends on the presence of.................... which, at least in animals, can only be derived from pyruvate (which is derived from glucose from glycolysis).
oxaloacetate
what are the steps in fatty acid degradation?
oxidation -> hydration -> oxidation -> cleavage - An activated fatty acid is oxidized to introduce a double bond. - The double bond is hydrated to introduce a hydroxyl group - The alcohol is oxidized to a keytone - The fatty acid is cleaved by coenzyme A to yield acetyl coA and a fatty acid chain two carbons shorter. (If the fatty acid has an even # of carbon atoms and is saturated, the process is repeated until the fatty acid is completely converted into acetyl CoA units)
Like glycolysis and gluconeogenesis, fatty acid degradation and synthesis are similar but not identical processes. Degradation is an................. process that converts a fatty acid into......................
oxidative a set of acetyl CoA units
The major product of fatty acid synthase is................. which is also the starting molecule to make longer fatty acids.
palmitate
Longer fatty acids are formed with............. as the starting molecule. They are formed by an elongation reaction by enzymes on the cytoplasmic face of the endoplasmic reticulum (ER). 2 carbon units are sequentially added to the carboxyl ends of saturated and unsaturated fatty acyl CoA substrates. ............................is the donor. The condensation reaction is driven by.........................
palmitate malonyl CoA decarboxylation of malonyl CoA
Elongation by fatty acid synthase stops on the formation of......................... Further modification steps such as elongation and the insertion of double bonds are carried out by other enzymes.
palmitate (C16)
How sphingolipids are synthesized?
palmitoyl CoA and serine condense to form 3-ketosphinganine. This is done by the enzyme serine-palitoyl transferase and the cofactor pyridoxal phosphate. This step releases CO2. Ketosphinganine is then reduced to dihydrosphingosine, before conversion into ceramide. In all sphingolipids, the amino group of ceramide is acylated and the terminal hydroxyl group is also substituted.
What are the different lipases and what common role do they play?
pancreatic lipases are intestinal enzymes. They break down triacylglycerols into fatty acids and monoacylglycerols so that they may be transported across the intestinal epithelium.
While most fatty acid degradation takes place in mitochondria, some can occur in................... What is this thought to do?
peroxisomes To promote the shortening of long fatty acid chains into octanoyl CoA which may be better substrates of β-oxidation in the mitochondria. Patients without these enzymes in peroxisomes die at a young age.
What is the key step for the synthesis of triacylglycerol?
phosphatidic acid phosphatase, a key enzyme in lipid synthesis, hydrolyzes phosphatidate to give diacylglycerol (DAG). Diglyceride acyltransferase adds an acyl group (a third fatty acid chain) to DAG to form triacylglycerol.
Sphingolipids are abundant in the cells of the central nervous system because there is lots of sphingomyelin in the myelin sheath. In sphingomyelin,.............................. is the substituent on the hydroxyl group of ceramide.
phosphorylcholine
What are the different synthetic schemes for synthesizing different steroids?
pregnenolone-> progesterone -> Either cortisol or corticosterone -> aldosterone
Fatty acid synthesis in bacteria: - Bacteria are capable of making odd number fatty acids as well as even number fatty acids. The synthesis of odd-number chain fatty acids will instead start with........................ - ............................ is the "condensing" enzyme. - The equilibrium for the synthesis of acetoacyl ACP is highly unfavorable. It is only favorable when malonyl ACP is a substrate because it can undergo decarboxylation. Thus, ATP drives the condensation reaction, though not directly. - Acetoacetyl ACP is reduced to become D-3-hydroxbutyryl ACP by............................. Note: the D- form and the use of NADPH.
propionyl ACP β-Ketoacyl synthase beta-ketoacyl reductase
The synthesis of fatty acids with an odd number of carbon atoms starts with........................
propionyl ACP.
Non-hepatic tissues get cholesterol from LDL thru............................ endocytosis. Expression of LDL receptor is regulated by.............
receptor mediated SREBP
Mitochondria are the source of acetyl CoA. They are also not permeable to the stuff. So,....................... in mitochondria produces much needed NADPH for fatty acid synthesis.
regeneration of Oxaloacetate
The β-oxidation pathway accomplishes the complete degradation of................... fatty acids with an................... number of carbon atoms.
saturated even
How ceremide is made, by what enzyme and what co-factor?
serine-palmitoyl transferase ( which is the rate limiting step) containing a pyridoxal cofactor.
What is the backbone of sphingolipids?
sphingosine
What are the roles of glucagon and epinephrine?
stimulate the release of fatty acids in fat cells which get released into the blood. They will inhibit acetyl CoA carboxylase through AMP-dependent kinase.
What are the roles of insulin?
stimulates the accumulation of fatty acids as triacylglycerols by muscle and adipose tissue. Insulin activates acetyl CoA carboxylase by stimulating Protein Phosphatase 2A.
Where and how are fatty acids stored?
stored in ester forms as triacylglycerols in adipose tissue.
During fatty acids synthesis, what are intermediates covalently linked to?
sulfhydryl groups of an acyl carrier protein (ACP)
Intermediates in fatty acid synthesis are covalently linked to........................ In degradation intermediates are linked to.........................
sulfhydryl groups of an acyl carrier protein (ACP) coenzyme A
What is the difference between fatty acid synthesis and degradation pathways?
synthesis and degradation are the same processes, but in reverse!
The acetyl CoA generated from fatty acid degradation is further processed in.......................
the citric acid cycle
Where does fatty acid synthesis happen?
the cytoplasm
The first step in the rearrangement Reaction Catalyzed by Cobalamin Enzymes is:
the homolytic cleavage of the carbon-cobalt bond of 5-deoxyadenosylcobalamin. This generates the Co2+ form of the enzyme and a 5' -deoxyadenosyl radical, -CH2*
In stage 2, while the transfer potentials of reactants (ATP) and products (thioester acyl CoA) are nearly equal, the reaction is driven forward by...................
the hydrolysis of pyrophosphate (PPi) into 2 Pi.
Which step is the committed step in cholesterol synthesis, and by which enzyme?
the synthesis of mevalonate by the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase).
How are the activated fatty acids transported into the mitochondrial matrix?
they are transported into the matrix by conjugation to Carnitine which is done by the enzyme, bound to the outer membrane, called carnitine acyltransferase I (also called carnitine palmitoyl transferase I, CPTI)
How do lipoproteins regulate the lipid trafficking in the body?
• Dietary fats are solubilized by forming complexes with cholesterol-like bile salts. • Dietary fats are packed in chylomicrons and delivered to adipose tissues from intestine. • Liver synthesized lipids and cholesterol which are packaged as VLDL. • As VLDL loses fatty acids it becomes more dense (IDL) and eventually LDL. • Remnants of phospholipids and cholesterol are packaged as HDL and sent to the liver for recycling.
Mevalonate is converted to 3-isopentenyl pyrophosphate in three ATP-driven steps:
• The first step is phosphorylation of the primary alcohol group at position 5. • Second step is the formation of pyrophosphate. • Third step is phosphorylation of tertiary alcohol at position 3.
Calculate the number of acetyl-SCoA molecules generated by complete beta oxidation of a 18-carbon activated fatty acid.
# of acetyl SCoA = (# of carbons in chain/2) so, answer is 9.
How do u calculate the number of repetitions of the B-oxidation pathway required to fully convert an 18-carbon activated fatty acid to acetyl-SCoA molecules?
# of repittions = (# of carbons in chain/2)-1 so, answer is 8.
Fats are sometimes used when carbs aren't. oxidation of a fatty acid produces about 38 kJ g-1. The complete oxidation of glucose or protein results in only 17 kJ g-1. Why is this?
(1) fatty acids are much more reduced than sugars. (2) triacylglycerols are nonpolar and anhydrous, whereas sugars are polar and therefore hydrated (this results in a huge increase in weight of sugar through water).
Perilipin is a fat-droplet associated protein that:
(1) restructures the fat droplet making the TAGs more accessible (2) triggers the release of a co-activator (CA) of adipose triglyceride lipase (ATGL).
What enzymes are involved in mobilizing fatty acids?
- ATGL (which initiates the mobilization by releasing a fatty acid from triacylglycerol, forming diacylglycerol. - Hormone-Sensitive lipase (which converts diacylglycerol into a free fatty acid and monoacylglycerol) - monoacylglycerol lipase (which completes the mobilization of fatty acids by producing a free fatty acid and glycerol from monoacylglycerol)
How does mammalian synthase complex work?
- An elongation cycle begins when MAT moves an acetyl unit from CoA to the ACP. - Beta ketosynthase (KS) accepts the acetyl unit which forms a thioester bond between the enzyme active site and the acetyl unit. - The vacant ACP is reloaded by MAT, this time with a malonyl moiety. -malonyl ACP accesses the beta KS active site where the condensation of the two 2-carbon fragments takes place and CO2 is released. (the selecting and condensing process ends up with the beta-ketoacyl product attached to ACP) - The β-ketoacyl product remains attached to ACP and next visits the modification compartment of the enzyme. - The β-keto group is reduced to -OH, dehydrated, and then reduced to yield the saturated acyl product (which is still attached to the ACP). - The reduced product then gets transferred to ketosynthase and ACP accepts another malonyl unit. - The process is repeated until the thioesterase releases the final C16 palmitic acid product.
A couple differences between fatty acid synthesis and degradation in bacteria:
- During synthesis, β-ketoreductase catalyzes the reduction of acetoacetyl ACP to D-3-hydroxybutyryl ACP (This is different from degradation in that the D isomer is formed instead of the L one). - NADPH is consumed in the biosynthetic reaction, whereas NADH is generated in energy-yielding reactions.
How is propionyl CoA converted into succinyl CoA so it can enter the citric acid cycle?
- In the first step, Propionyl CoA is carboxylated using the energy from ATP hydrolysis. This is catalyzed by Propionyl CoA carboxylase, a biotin enzyme. - Next, the D isomer of methylmalonyl CoA is racemized to the L isomer. - In the last step, the L isomer is converted to Succinyl CoA by methylmalonyl CoA mutase, catalyzing an intramolecular rearrangment using a cobalamin coenzyme.
How do things like cupcakes become part of you?
- Once separated, fatty acids and monoacylglycerols can be transported across the intestinal epithelium. - Once across the plasma membrane, triacylglycerides are reformed and are incorporated into lipoprotein particles called chylomicrons, with apoliproteins such as B-48. Protein constituents in lipoprotein particles are apolipoproteins. - Chylomicrons can enter the blood where they bind to membrane-bound ligases on adipose tissue and muscle, broken down into fatty acids and monoacyl glycerol, transported into the tissues, and re-synthesized into triacylglycerol and stored.
What are the 5 different types of steroid hormones?
- Progesterone - Androgens (testosterone) - Estrogens (estradiol) - Glucocorticoids - Mineralocorticoids (aldosterone)
What are the steps of converting propionyl CoA to succinyl CoA?
- Propionyl CoA is carboxylated which makes methylmalonyl CoA. - The D isomer of methylmalonyl CoA is racemized to the L isomer. - The L isomer of Methylmalonyl CoA is converted to Succinyl CoA.
Where does NADPH come from for the synthesis?
- Regeneration of Oxaloacetate in mitochondria creates NADPH, so there are 8 NADPH formed when 8 acetyl CoA are transferred from mitochondria to the cytoplasm for the synthesis of palmitate. -The additional 6 NADPH molecules are from the Pentose Phosphate pathway.
What are the reaction steps in fatty acid synthesis?
- Some acetyl CoA will become malonyl CoA (enzyme: acetyl CoA carboxylase) - Then, acetyl CoA and malonyl CoA will become acetyl ACP and malonyl ACP. (enzymes: acetyl transacylase & malonyl transacylase) - Both of these will combine, forming acetoacetyl ACP, releasing an ACP and CO2. (beta-ketoacyl synthase) - Acetoacetyl ACP and NADPH will form d-3-hydroxybutyryl ACP. (beta-ketoacyl reductase) - This will undergo dehydration to form crotonyl ACP and H20. (3-hydroxyacyl dehydratase) - crotonyl ACP and NADPH will form butyryl ACP. (enoyl reductase)
during the reduction step where Acetoacetyl ACP and NADPH form d-3-hydroxybutyryl ACP, this reaction differs from the corresponding one in fatty acid degradation in what ways?
- The D isomer is formed in synthesis (L is in degradation) - NADPH is the reducing agent (NAD+ is oxidizing agent in degradation)
What are other mechanisms that regulate cholesterol synthesis?
- The rate of translation of reductase mRNA is INHIBITED by non sterol metabolites derived from mevalonate - The degradation of the reductase is tightly controlled by binding to Insig when sterol concentrations are high, and then the ubiquitin-proteasome system ubiquinates it, removes it from the membrane, and then it is degraded by a proteasome. - Phosphorylation decreases activity of HMG-coA reductase. Regulation is similar to acetyl CoA carboxylase (enzyme that synthesizes malonyl CoA used in fatty acid synthesis). It gets phosphorylated by AMPK to reduce its activity when there are low ATP levels.
Palmitoyl CoA is a negative allosteric effector of:
- acetyl CoA carboxylase (causing the active oligomers to disassemble) - glucose-6 dehydrogenase (preventing it from generating NADPH from the pentose phosphate pathway) - the translocase that transports citrate into the cytoplasm from the mitochondria.
What is Palmitoyl CoA a negative allosteric effector for?
- acetyl CoA carboxylase, causing the active oligomers to disassemble. - glucose-6 dehydrogenase from generating NADPH from the pentose phosphate pathway - the translocase that transports citrate into the cytoplasm from the mitochondria.
Why are the ketone bodies produced in the liver so important?
- heart muscle cells actually prefer this stuff to glucose. - the brain can adapt to using acetoacetate during starvation and diabetes (75 % of the fuel needs of the brain are met by ketone bodies when in prolonged starvation)
Stage 3 involves the generation of Acetyl CoA, NADH, and FADH2 during the β-oxidation pathway. What are the 4 rxns that do this?
- oxidation by FAD. - hydration. - oxidation by NAD+. - thiolysis by coenzyme A.
What reaction steps are required for each round of fatty acid oxidation, and by what enzymes?
- oxidation of acyl CoA by acyl CoA dehydrogenase, with FAD as the electron acceptor. - hydration by enoyl CoA hydratase - oxidation by L-3-hydroxyacyl CoA dehydrogenase with NAD+ as the acceptor. - thiolysis with coenzyme A and B-ketothiolase
Note that there are a few different acyl-CoA dehydrogenases. They are:
- the long chain acyl-CoA dehydrogenase, C12-C18; - medium chain acyl-CoA dehydrogenase, C14-C4; - short-chain acyl-CoA dehydrogenase, which acts only on 4- and 6-carbon fatty acid chains.
Glucose is an important fuel, but fatty acids are important also! Fatty acids have 4 major physiological roles:
- they are fuel (during rest or moderate exercise, fatty acids are humans primary source of energy). - building blocks of phospholipids and glycolipids. - target proteins to the membrane through covalent modification. - converted into derivatives that serve as hormones and/or intracellular messengers.
What are physiological roles of fatty acids?
- they are fuel/primary source of energy during rest or moderate exercise. - building blocks of phospholipids and glycolipids. - can target proteins to the membrane through covalent modification. - can be converted into derivatives that serve as hormones and intracellular messengers.
What happens to the electrons once they are transferred to FAD creating FADH2?
-Electrons from the FADH2 are transferred to a second flavoprotein: the electron-transferring flavoprotein (ETF). -ETF donates electrons to ETF:ubiquitinone reductase, which is an iron-sulfur protein. -electrons are used to reduce ubiquinone to ubiquinol to be further oxidized in the oxidative phosphorylation chain on the mitochondrial membrane. -Each FADH2 produces 1.5 ATP.
What happens to the electrons during stage 3?
-Electrons from the FADH2 are transferred to second flavoprotein: the electron-transferring flavoprotein (ETF). -ETF donates electrons to ETF:ubiquitinone reductase, an iron-sulfur protein. -electrons is used to reduce ubiquinone to ubiquinol to be further oxidized in the oxidative phosphorylation chain on mitochrondrial membrane
What are different types of membrane lipids to be synthesized?
-Phospholipids (including triacylglycerols) -Sphingolipids -Cholesterol
Human cannot convert fatty acid to glucose. Why?
-acetyl CoA cannot be converted to pyruvate. -acetyl CoA cannot be used to de novo synthesize oxaloacetate.
Why can't fatty acids be converted into glucose?
-acetyl CoA cannot be converted to pyruvate. -acetyl CoA cannot be used to de novo synthesize oxaloacetate.
phosphatidylcholine is the most common phospholipid. What are the 2 ways to make it?
-from dietary choline. -from phosphatidylethanolamine.
What is the advantage to using fatty acids as the primary storage fuel as compared with glycogen?
1 gram of fat stores about 6.75 times as much energy as 1 gram of hydrated glycogen.
So, why is mammalian fatty acid synthase a multi-functional enzyme?
1) Coordinates the synthetic activities of multiple enzymes. 2) Intermediates can be efficiently handed from one active site to the other without leaving the enzyme assembly. 3) It is more stable than a protein complex.
So, why the multi-functional enzyme?
1) Coordinates the synthetic activities of multiple enzymes. 2) Intermediates can be efficiently handed from one active site to the other without leaving the enzyme assembly. 3) More stable than a protein complex.
Enyzmes for ketone body formation:
1) ketothiolase 2) hydroxymethylglutary CoA synthase 3) 3-hydroxy-3-methyl glutaryl CoA cleavage enzyme 4) D-3-hydroxybutyrate dehydrogenase. Acetoacetate spontaneously but slowly decarboxylates to acetone.
What are the three stages of fatty acid processing as a fuel?
1- Triacylglycerols are degraded to fatty acids and glycerol, which are then released from adipose tissue and transported to energy-needy tissues. 2- Fatty acids are activated and transported into mitochondria for degradation. 3- Fatty acids are then broken down into acetyl CoA which is a substrate of the citric acid cycle.
How is cholesterol synthesized?
1. Stage one is the synthesis of isopentenyl pyrophosphate from acetyl CoA in the cytoplasm. 2. Stage 2 is the condensation of six isopentenyl pyrophosphate molecules to form squalene in ER. 3. In stage 3 squalene cyclization occurs and forms lanosterol and the product is converted to cholesterol in ER.
Biosynthesis of cholesterol occurs in what three stages?
1. Synthesis of isopentenyl pyrophosphate in cytoplasm. 2. Condensation of six isopentenyl pyrophosphate molecules to form squalene in ER. 3. Squalene cyclization forms lanosterol and the product is converted to cholesterol in ER.
While fatty acid synthesis is the reversal of the degradative pathway in terms of chemical reactions, the synthesis and degradation pathways are different mechanistically. What are the differences in fatty acid synthesis as compared with degradation?
1. Synthesis takes place in the cytoplasm, while degradation takes place in the mitochondrial matrix. 2. Intermediates in fatty acid synthesis are covalently linked to sulfhydryl groups of an acyl carrier protein (ACP); in degradation intermediates are linked to that of coenzyme A. 3. In higher organisms, fatty acid synthase is a mega-enzyme that contains multiple enzymatic functions in one long polypeptide chain. degradative enzymes are not associated. 4.The growing fatty acid chain is elongated by the sequential addition of acetyl groups derived from acetyl CoA. The activated donor of two carbon unit in elongation is malonyl ACP and the reaction is driven by release of CO2. 5. The reductant in fatty acid synthesis is NADPH, while the oxidants in fatty acid degradation are NAD+ and FAD+. 5. Elongation by fatty acid synthase stops on the formation of palmitate (C16). Further modification steps such as elongation and the insertion of double bonds are carried out by other enzymes.
Cobalamin (Vitamin B12) containing enzymes (such as methylmalonyl CoA mutate) do what?
1. catalyze intra-molecular rearrangements *** 2. methylations 3. The reduction of ribonucleotides to deoxyribonucleotides.
Each FADH2 produces........... ATP.
1.5
Degradation of palmitate (C16) through the β-oxidation pathway produces how many ATP?
106 ATP
What many ATPs are produced by the complete oxidation of palmitate?
106 ATP molecules
In a healthy person, the HDL/LDL ratio is.......
3.5
