The Big Daddy MCB 354 Exam 4 Flashcard Set

Biocchem unites 29 through 38.

What are the three sources of fatty acids for cellular use?

Fats stored in cells as lipid droplets, fats synthesized in one organ and exported to another, and dietary fat.

What are the two advantages of triacylglycerol-based stores?

High energy content and compact

What is the disadvantage of triacylglycerol-based stores?

Insoluble in water; requires special handling for transporting fats between tissues

Where are lingual and gastric lipases produced and what level of dietary fat digestion occurs by them?

They are produced in the back of the tongue or in the stomach and catalyze a low level of digestion.

What are lingual and gastric lipases?

Estrases that are responsible for digesting triacylglycerols into short and medium chain fatty acids.

Who are lingual and gastric lipases most active in?

Infants and young children who drink cows milk.

What enzymes and procesees catalyze a more extensive digestion of lipids than lingual and gastric lipases and where does it occur?

Bile salts, pancreatic lipases, and peristalsis digest lipids in the small intestine.

How does Cystic Fibrosis affect lipid digestion?

Mutations in the CFTR prevent the pancreatic lipases synthesized in the pancreas from reaching the small intestine to digest lipids and the lingual and gastric lipases are thus more heavily relied on.

How does a detergent differ from a phospholipid?

A phospholipid has one polar head with two non polar tails and is cylindrical while a detergent has one polar head with one non polar tail and is wedge shaped.

How is the self-assembly of detergents different from phospholipids?

Phospholipids assemble into a bilayer while detergents assemble into a spherical micelle due to their wedge shape.

How do detergents emulsify lipids?

They form mixed micelles which increase the surface to volume ratio of fat droplets by breaking up large fat globules into small spherical micelles, accelerating the digestion of lipids by lipases.

What is the structure of mixed micelles?

Detergents assembled in a spherical micelle with their polar heads facing outwards and their non polar tails facing into a center containing lipids.

What are bile salts?

Detergents synthesized from cholesterol in the liver that form emulsions(mixed micelles) with lipids.

Lipid emulsification is accomplished through what two complementary mechanisms?

Use of the detergent properties of bile salts and mechanical mixing due to peristalsis.

Where are bile salts stored and where are they secreted to?

They are stored in the gallbladder and secreted to the small intestine in the form of bile.

After the emulsification of lipids in the small intestine what process must occur?

The emulsified triacylglyerols and other lipids must be hydrolyzed in the small intestine by pancreatic lipases that are secreted by the exocrine pancreas; free fatty acids are released.

Pancreatic lipases preferentially remove fatty acids at what carbons of the triacylglycerol?

Carbons 1 and 3.

What is the action and purpose of colipase (zymogen) in lipid digestion?

it binds pancreatic lipase in a 1 to 1 ratio and anchors it to the lipid aqueous interphase.

What does the drug, Orlistat, do?

Fights obesity by inhibiting the function of gastric and pancreatic lipases which decreases fat absorption.

What is the cholesterol esterase reaction?

Cholesterol esters are hydrolyzed by pancreatic cholesterol esterase to produce cholesterol plus free fatty acids.

What is cholesterol esterase activity greatly increased by?

Bile salts.

How are phospholipids degraded by pancreatic enzymes?

First, phospholipase A2 removes 1 fatty acid from carbon 2 leaving a lysophospholipid; next, the fatty acid at carbon 1 is removed by lysophospholipase resulting in a glyceryl-phosphoryl base that is either further degraded, absorbed, or excreted.

What is the degradation of phospholipids enhanced by?

Bile salts.

Where is the hormone, cholecystokinin (CKK), produced and what does it control?

It is produced by the mucosal cells in the jejunum and acts on the stomach to slow gastric motility, the gallbladder to contract and release bile, and the pancreas to release the pancreatic lipase.

What is the hormone, secretin, produced in response to and what does it cause?

It is produced in response to the low pH of chyme entering the duodenum from the stomach and it causes the pancreas and liver to release bicarbonate to neutralize the pH of intestinal contents.

After lipid soluble compounds have been and emulsified by bile salts, packaged into micelles, and degraded by intestinal lipases, what process must occur next in digestion?

They must be absorbed by intestinal mucosal cells.

What are all the compounds that micelles contain?

2-monoacylglycerols, fatty acids, free cholesterol, and the fat soluble vitamins A, D, E, and K.

What is steatorrhea and what are its possible causes?

It is excess lipid in feces and is possibly caused by disturbances in lipid digestion and/or absorption due to cystic fibrosis or a shortened bowel.

What is Olestra (Olean)?

An artificial fat substitute with a structure containing a sucrose molecule with esterified fatty acids that is resistant to pancreatic lipase and passes through the intestinal tract until it is eliminated in the feces.

What is the problem with Olestra (Olean)?

It also carries essential fat-soluble vitamins with it.

What is the action of intestinal epithelial (mucosal) cells in lipid digestion?

Absorb fatty acids and other breakdown products and use them to re-synthesizes triacylglycerols and cholesterol esters and package them into chylomicrons.

What are the steps in the conversion of fatty acids and other breakdown products to triacylglycerols in the intestinal epithelial cells?

Lipids absorbed by the enterocytes migrate to the endoplasmic reticulum, fatty acids are activated by fatty acyl-CoA synthetase (thiokinase), 2-monoacylglycerols are converted to triacylglycerols by mono and diacylglycerol acyltransferases, lysophospholipids are re-acylated to form phospholipids by acyltransferases, and cholesterol is re-esterified by acyl CoA:cholesterol acyltransferase but short and medium chain fatty acids are not re-esterified.

What are lipoprotein particles?

Particles with an exterior of apolipoproteins and a phospholipid monolayer and an interior of the lipid payload that functions as a structural component, to activate enzymes, and to help recognition of a receptor.

What are chylomicrons?

Particles with an exterior of apolipoproteins and a phospholipid monolayer and an interior of the re-synthesized triacylglycerols, cholesterol esters, and fat-soluble vitamins and functions to deliver dietary fats from the intestinal epithelial cells to the tissues

What is the function of lipoprotein lipase?

Once activated by AppC-II (apolipoprotein) in the capillary, it converts triacylglycerols to fatty acids and glycerol.

How does the activity of lipoprotein lipase differ in adipose tissue and muscle cells.

The lipoprotein lipase of adipose tissue has a higher Km than that of muscle cells so adipose lipoprotein lipase is more active than muscle cell lipoprotein lipase following a meal but muscle lipoprotein lipase is more active than adipose lipoprotein lipase at lower triacylglycerol/chylomicron levels and can more reliably use fatty acids for energy.

In the liver, what is the fate of the glycerol synthesized from the action of lipoprotein lipase?

Unlike other tissues, the liver has glycerol kinase, which can be used to convert glycerol to glycerol 3-phosphate which can then be used for glycolysis or gluconeogenesis.

During fasting, how are the fatty acids released from triacylglycerols stored in the adipose?

Glucagon and epinephrine cause the activation of a hormone-sensitive lipase, free fatty acids and glycerol are released into the blood, and free fatty acids circulate bound to serum albumin which are used for energy by various tissues.

What is the central role of lipoprotein particles by the liver?

They help with lipid transport.

What are the four types of lipoprotein particles and what are they secreted by?

Chylomicrons are secreted by the intestine, VLDLs are converted to LDLs and are secreted by the liver, and HDLs are secreted by the liver and intestine.

What are the triacylglycerol and cholesterol compositions of each of the four lipoprotein particles?

HDLs have the lowest triacylglycerols and high cholesterol, VLDLs have low triacylglycerols and the highest cholesterol, LDLs have high triacylglycerols and low cholesterol, and chylomicrons have the highest triacylglycerols and lowest cholesterol.

What are the functions of each of the four lipoprotein particles?

HDLs deliver cholesterol from the peripheral tissues to the liver for elimination, LDLs deliver cholesterol to the peripheral tissues and to the liver, VLDLs deliver endogenous triacylglycerols to peripheral tissues, and chylomicrons deliver dietary (exogenous) triacylglycerols to peripheral tissues.

What are the steps of the exogenous pathway of chylomicron metabolism?

They are synthesized in the liver, pick up apoE and apoCs from HDL, have their triacylglycerol degraded to fatty acids and glycerol by lipoprotein lipase in the adipose tissue, their remnants bind apoE receptors on the surface of liver cells where their complex is endocytosed, the remnants then deliver dietary cholesterol and some cellular cholesterol to the liver, and are cleared from circulation in over 9 hours.

What are chylomicron remnants?

Chylomicrons depleted of triacylglycerols.

What are the steps of the endogenous pathway of VLDL and LDL metabolism?

The liver packages triacylglycerols and cholesterol into VLDL particles for export, their triacylclycerol is degraded to free fatty acids and glycerol in the capillaries, the fatty acids are delivered to the tissues by LDL, LDL binds its receptor on the surface of the tissues, and enter the peripheral tissues via diffusion delivering their cholesterol content to the cells.

What are IDLs?

VLDL remnants

What enzyme converts IDLs to LDLs and what do they then contain?

Lipoprotein lipase converts IDLs to LDLs which mostly contain cholesterol esters at this point.

Why is LDL cholesterol referred to as "bad cholesterol"?

High levels of LDL cholesterol are correlated with an increased risk of cardiovascular disease (atherosclerosis).

What are the steps of the reverse pathway of HDL particles?

The particles are secreted by the liver and intestine as empty (nascent) particles, they diffuse close to the peripheral cell membranes where they pick up cholesterol, mature HDL that is full of cholesterol binds receptors on adrenal cells, gonads, and liver thus delivering cholesterol to these tissues.

Why is HDL cholesterol referred to as "good cholesterol"?

Their cholesterol levels are inversely related to risk of cardiovascular disease.

What is Tangier disease?

A rare autosomal reccesive condition characterized by low levels of HDL cholesterol in the blood, accumulation of cholesterol in many organs of the body, and an increased risk of arteriosclerosis; symptoms include large yellow-orange colored tonsils engorged with cholesterol, an enlarged spleen and liver, eye abnormalities, and neurological abnormalities.

What is familial lipoprotein lipase deficiency (Type I hyperlipidemia)?

A rare autosomal recessive disorder caused by a deficiency in lipoprotein lipase or its coenzyme, apoldprotein C-II.

What is familial hypercholesterolemia (Type II hyperlipidemia)?

A very common condition characterized by high LDL cholesterol levels that is mainly caused by mutations in the LDLR gene which normally removes LDL or apoldprotein B (the part that binds to the receptor) from circulation.

What is familial dysbetalipoproteinemia "remnant hyperlipidemia" (Type III hyperlipidemia)?

A condition where the removal of chylomicron remnants by the liver is decreased due to impaired binding to their receptor, resulting in them accumulating in the plasma.

What confirmation are the unsaturated C=C double bonds in fatty acids almost always in?

The cis confirmation.

What number of carbon atoms do most fatty acids in our cells have?

An even number.

Where does the synthesis of fatty acids occur?

In the cytosol, primarily in the liver and lactating mammary gland, less so in adipose tissue.

What are fatty acids synthesized from?

They are synthesized from acetyl CoA derived from excess protein and carbohydrate.

What is used as an energy source for fatty acid synthesis?

ATP and NADH.

The conversion of excess carbohydrates to fatty acids is unregulated by what horemone?

Insulin induces the enzymes needed.

What mediates the reciprocal regulation of pyruvate carboxylase and pyruvate dehydrogenase?

Acetyl CoA

How is the acetyl CoA transferred from the mitochondria to the cytosol for fatty acid synthesis?

By the citrate shuttle.

What triggers the citrate shuttle?

Occurs when the citrate concentration in the mitochondria is high due to inhibition of isocitrate dehydrogenase by high levels of ATP.

In fatty acid synthesis, what is the series of reactions that occur in order to produce an activated acyl group lengthened by 2 carbons from an activated acyl group and an activated malonyl group?

A condensation reaction, then a reduction reaction, then a dehydration reaction, and finally another reduction reaction.

What is the first step of fatty acid biosynthesis?

The synthesis of malonyl CoA from acetyl CoA

What are the purposes of first synthesizing malonyl CoA in fatty acid biosynthesis?

To indirectly supply the energy needed to form two more C-C bonds in later steps, to act as the 2-carbon donor for later steps, to inhibit fatty acid oxidization through the inhibition of CPT-I, and to prevent futile cycling.

What enzyme catalyzes the conversion of acetyl CoA to malonyl CoA and what else does it require for the reaction?

Acetyl CoA carboxylase catalyzes the reaction and uses ATP and CO2 with a cofactor of biotin.

Why is the conversion of acetyl CoA to malonyl CoA important in terms of the regulation of fatty acid biosynthesis?

It is the first committed step of the pathway and is also highly regulated.

For the acetyl CoA to malonyl CoA reaction of fatty acid biosynthesis, how is the biotin cofactor attached to the biotin carrier protein?

It is attached to a lysine of the carrier protein.

What are the components of the multi-functional enzyme complex that catalyzes the first reaction of fatty acid biosynthesis?

Transcarboxylase (Acetyl-CoA carboxylase), biotin, biotin carrier protein, and biotin carboxylase.

how many active sites are there in the multi-functional enzyme complex that catalyzes the first reaction of fatty acid biosynthesis and how is it regulated?

There are three active sites and it is highly regulated by protein phosphorylation.

What is the rate limiting step of fatty acid biosynthesis?

The production of malonyl-CoA from acetyl-CoA.

What are the allosteric activators and deactivators of Acetyl-CoA carboxylase?

Citrate activates it and fatty acyl CoA (palmitate) deactivates it.

What are the activators and deactivators of Acetyl CoA carboxylase through phosphorylation?

Phosphorylation of the enzyme in response to epinephrine, c-AMP, and protein kinase cascade deactivates it while dephosphorylation in response to insulin activates it.

After the malonyl CoA synthesis reaction, what enzyme complex are the rest of the reactions in fatty acid biosynthesis carried out by?

The fatty acid synthase complex.

How is the fatty acid synthase complex different in humans compared to bacteria, plant, and yeast?

In humans, there are multiple enzymatic activities on one single polypeptide chain whereas in bacteria, plant and yeast there is the same enzymatic activity on more than one polypeptide chains.

What are all the enzymes in the fatty acid synthase complex?

Beta-ketoacyl-ACP synthase, beta-hydroxyacyl-ACP dehydratase, enoyl-ACP reductase, beta-ketoacyl-ACP reductase, malonyl/acetyl-CoA-ACP transferase, and ACP (acyl carrier protein).

What is the purpose of acyl carrier protein in the fatty acid synthase complex?

It moves intermediates between active sites.

How many -SH tethering sites are there on the fatty acid synthase complex?

Two.

How are the intermediates in fatty acid synthesis attached to ACP?

Through a long chain -SH group of the fatty acid synthesis complex.

How are the phosphopantetheine prosthetic groups of ACP and coenzyme A (CoA) similar and different?

They are identical except that it is covalently attached to a serine in ACP instead of being attached to an adenosine diphosphate as in CoA.

What must first happen before the fatty acid synthase complex can act?

The enzyme must first be charged with an acetyl group from acetyl CoA.

What occurs in the first charging reaction?

Malonyl/acetyl-CoA-ACP transferase (MAT) transfers the acetyl group from acetyl CoA to ACP which is then transferred to the -SH tether on the beta-ketoacyl-ACP synthase (KS) across the fatty acid synthase complex.

What occurs in the second charging reaction?

MAT transfers the malonyl group from malonyl CoA to ACP.

How many times is the cycle of condensation, reduction, dehydration, and then another reduction reaction repeated and what product is desired?

Seven times until palmitate is produced.

What occurs in the condensation reaction of fatty acid biosynthesis?

KS catalyzes the carboxylation of the C-2 carbon of the malonyl to make it a good nucleophile so that it can attack the acetyl through decarboxylation.

What occurs in the first reduction reaction of fatty acid biosynthesis?

Beta-ketoacyl-ACP reductase (KR) catalyzes the reduction of the Beta-keto group with a D-stereochemistry intermediate.

What occurs in the dehydration reaction of fatty acid biosynthesis?

Beta-hydroxyacyl-ACP dehydratase (DH) catalyzes the removal of the -OH group as H2O.

What occurs in the second reduction reaction of fatty acid biosynthesis?

Enoyl-ACP reductase (ER) catalyzes the reduction of the double bond using power from NADPH to produce a 4-carbon saturated fatty acid (butyrate) attached to ACP.

In order for the cycle of a condensation, reduction, dehydration, and a reduction reaction to repeat, what first needs to happen?

The butyryl group on the ACP needs to be moved to the -SH tether on the KS of the fatty acid synthase complex and the complex must be recharged with a malonyl group.

In hepatocytes (the site of most fatty acid biosynthesis in humans), what are the approximate ratios of reduced to oxidized NADPH/NADP+ and NADH/NAD+ in the cytosol?

10/1 and 1/1000, respectively.

What are the sources of NADPH for fatty acid synthesis?

The pentose phosphate pathway and the magic enzyme reaction that converts malate to pyruvate + NADPH in the cytosol.

How is acetyl CoA moved from the mitochondrial matrix into the cytosol for fatty acid synthesis?

It is moved into the cytosol as citrate and once in the cytosol is converted back to OAA + acetyl CoA and the OAA produced is further converted to malate; the malate produced is then converted into pyruvate + NADPH which are then shuttled back out to the mitochondria

Where does the elongation and desaturation of palmitate take place?

Elongation takes place in the mitochondria and the endoplasmic reticulum and desaturation takes place in the endoplasmic reticulum.

What occurs in the fatty acyl elongation reactions in the smooth endoplasmic reticulum?

Fatty acid chains are elongated by 2 carbons at a time from acetyl CoA.

What occurs in the fatty acyl desaturation reactions?

New carbon-carbon double bonds are introduced.

What are the limits to how many double bonds can be introduced to fatty acids in desaturation?

Mammals cannot introduce C=C double bonds beyond carbon 9 but plants can so we can synthesize palmitoleate (7) and oleate (9) but not linoleate (3) or (6).

What is the action of fatty acyl-CoA in vertebrates?

Converts saturated fatty acyl-CoA to monounsaturated fatty acyl-CoA creating a double bond.

How is respiratory distress syndrome caused?

The failure to synthesize enough DPPC, an important component of lung surfactant, that works to prevent the collapse of lung at the end of the expiration phase of breathing.

In the fed state, what are the up-regulators of the synthesis of triacylglycerols from fatty acids and glycerol for storage in adipose?

Insulin, a surplus of glucose in the blood, and high amounts of apolipoprotein C-II.