Chapter 22: Fatty acid and Tricylglycerol Metabolism

Fatty acids have what major physiological roles?

1. Fatty acids are fuel molecules (primary source of energy for moderate exercise and also rest)

2. Fatty acids are building blocks of phospholipids and glycoplipids

3. Many proteins are modified by the covalent attachement of fatty acids, which functions to target proteins to memebrane locations

4. Fatty acid derivatives serve as hormones and intracellular messengers

Triacylglyceorls are highly

Concentrated energy stores

What are triacylgylserols (triglycerides)

Uncharged esters of fatty acids with glycerol

Triacylglycerols are stored mainly in?

Adipose tissue

Triacylglycerols stored also by?

Muscle for energy needs

Triacylglycerols are highly concentrated stores of … Why?

Metabolic energy because they are reduced and contain no water

What is adipose tissue?

Fuel-rich, white tissue that is located throughout the body, under skin (subcutaneous fat) and surrounding internal organs (visceral fat)

What are adipocytes?

Fat cells that make up adipose tissue

What is the major site of triacylglycerol accumulation?

Adipocytes

Adipocytes are specialized for?

Triacylglycerol synthesis, storage, and mobilization into fuel

What are lipid droplets?

Large globules formed by the coalescence of triacylglycerols

Dietary lipids are digested by?

Pancreatic lipases

What is lipases?

Intestinal enzymes that degrade triacylglycerols to free fatty acids and monoacylglycerol

Lipases are secreted by?

The pancrease

Lipids exit the stomach as an emulsion

Particles with a triacylglycerol core surrounded by cholestrol and cholesterol esters

What are bile acids?

Ampithatic molecules that facilitate lipid digestion by lipases

Bile acids are synthesized from?

Cholesterol in the liver and secreted from the gallbladder

Bile acids orients?

Ester bonds to make them more accessible to digestion by lipases in aqueous solution

What is colipase?

Protein that binds lipase to the particle to permit lipid degradation

Colipase is secreted by?

The pancreas

In the intestine, triacylglycerols are reformed from?

Free fatty acids and monoacylglycerols and packaged into lipoprotein particles called chylomicrons

The chylomicrons eventually..

Enter the blood so that the triacylglycerols can be absorbed by tissues

Free fatty acids and monoacylglucerols are transported in?

Micelles to the plasma membrane of intestinal epithelial cells

What are fatty acid transport proteins?

Membrane protein transports that transport free fatty acids and monoacylglycerols inside the membrane

What are fatty acid binding proteins?

Proteins that ferry free fatty acids and monoacylglycerols to the cytosolic face of the smooth ER for resynthesis of triacylglyceorls

What are chylomicrons?

Lipoprotein transport particles composed of newly synthesized triacylglycerols, with proteins, phospholipids, and cholesterol on the surface

Chylomicrons are released into?

The blooc

Chylomicrons are degraded by?

Membrane bound lipases at adipose tissue and muscles

The use of fatty acids as fuel requires how many stages of processing?

3

What is stage 1 ?

(Mobilization of lipids through triacylglycerol degradation to fatty acids and glycerol, release from adipose tissue, and transport to the energy requiring tissues

What is stage 2?

Activation of the fatty acids and transport into the mitochondria

What is stage 3?

Degradation fo fatty acids to acetyl CoA for processing in the CAC

What is mobilization?

Triacylglycerols are hydrolyzed by hormone-stimulated lipase

Hormonally controlled lipases catalyze the

Hydrolysis of triacylgloycerol to fatty acids

Glucogen and epinephrine act through 7TM receptors, leading to..

Phosphorylation of 2 proteisn by PKA

What are the 2 proteins?

1 PERILIPIN

2 HORMONE-SENSITIVE LIPASE

What is perilipin?

A fat droplet associated protein

Phosphorylated perilipin restructues the fat droplet so?

The triacylglycerols are more accessible to mobilization

Phosphorylation of perilipin triggers?

The release of a coactivator for adipose triglyceride lipase

What is ATGL?

Initiates mobilization by releasing a fatty acid from triacylglycerol, forming diacylglycerol, when bound to its coactivatore

Hormone sensitive lipase converts

Diacylglycerol into a free fatty acid and monoacylglycerol

What is monoacylglycerol lipase?

Converts monoacylglycerols into a free fatty acid and glycerol

Monoacylglycerol lipase completes?

Fatty acid mobilization

In monoacylglycerol lipase, ethanol can inhibit?

The signaling pathway, leading to fatty liver disease

Triacyglycerols in adipose tissue are converted into

Free fatty acids in response to hormonal signals

Free fatty acids and glycerol are released into

The blood

What is albumin?

Proteins that transports fatty acids in teh blood

Glycerol is absorbed by the liver where it is?

Phosphorylated, oxidized to dihydroxyacetone phosphate, and isomerized to glyceraldehyde 3-phosphate

Lipolysis generates?

Fatty acids and glycerol

Depending on metabolic needs, the liver processes glycerol by?

The glycolytic or gluconeogenic pathway

What is activation?

Fatty acids are linked to coenzyme A before they are oxidized

Fatty acids enter?

Intestinal cells are are transported within the cell to the mitochondria

What is acyl CoA synthetase?

Catalyzes the activation of fatty acids through the formation of thioester linkage to coenzyme A

Acyl CoA synthetase requires?

ATP

Acyl CoA synthetase takes place on?

The outer mitochondrial membrane

What is transport?

Carnitine carries long chain activated fatty acids into the mitochondiral matrix

What is carnitine?

An alcohol with both a positive and a negative charge

In transport, fatty acids must be what to be transported across the inner mitochondiral membranesri

Fatty acids must be conjugated to carnitine

Acyl carnitine translocase mediates?

The entry of acyl carnitien into the mitochondiral matrix

What is breakdown?

Acetyl CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation

The b oxidation pathway consists of how many steps that are repeated?

4

What are the steps?

1. Oxidation by FAD

2. Hydration

3. Oxidation by NAD+

4. Thiolysis by coenzyme A

In breakdown, each repetition shortens..

The fatty acid chains by 2 carbons

Why is it called the B oxidation pathway because?

Oxidation occurs at the B carbon atom

Unsaturated and odd chain fatty acids require additional steps for?

Degredation

B oxidation alone can or cannot degrade unsaturated fatty acids

Cannot

When monounsaturated fatty acids are degraded by B-oxidation, what is formed?

cis-Δ3-enoyl CoA, which is not a substrate for acyl CoA dehydrogenase

cis-Δ3-enoyl CoA isomerase converts?

The double bond into a trans-Δ2 double bond, yielding trans-Δ2-enoyl CoA,
a normal substrate for β-oxidatin

Unsaturated fatty acids with odd numbers of double bonds require only

The isomerase

Odd chain fatty acids yield?

Propionyl CoA int he final thiolysis step

B ocidation of fatty acids with odd numbers of carbons generates?

Propionyl CoA in the final round of degradation

The activated 3 carbon unit in propionyl CoA is converted into

Succinyl CoA

Succinyl CoA can?

• enter the citric acid cycle

• be converted into oxaloacetate to provide carbon for glucose biosynthesis

Fatty acids are also oxidized in

Peroxisomes

What are peroxisomes?

Small membrane bounded organelles present in most eukaryotic cells

Oxidation of long chain and branched fatty acids takes place in?

Peroxisomes

Oxidation of long chain and branched fatty acids takes
place in peroxisomes functions to..?

Shorten very long chains to make them better substrates of B-oxidation in mitochondria

Oxidation of long chain and branched fatty acids takes
place in peroxisomes, oxidation halts with?

The formation of octoanyl CoA

Ketone bodies are a fuel source derived from?

Fats

acetyl CoA formed in fatty acid oxidation enters the CAC only if?

Fat and carbohydrate degradation are balanced

In fasting or diabetes, oxaloacetate is consumed to from?

Glucose in the glucoeneogenic pathway

In fasting or diabetes, acetyl CoA is diverted to form

acetoacetate and D-3hydroxybutyrate

What are ketone bodies?

Acetoacetate, D-3-hydroxybutyrate, and acetone

• water soluble, transportable forms of acetyl units

Abnormally high levels of ketone bodies are present in?

The blood of untreated diabetics

The liver supplies ketone bodies to the

Peripheral tissues

Fatty acids are synthesized by?

Fatty acid synthase

What are fatty acid synthase?

A complex of enzymes that synthesize fatty acids

Many tissues, such as liver and adipose tissue are capable of

Synthesizing fatty acids

Most humans get enough fatty acids from

The diet

Fatty acid synthesis is required under certain physiological condnitions?

Example:

• during embryonic development

• During lactation in mammary glands

Are the steps in fatty acids degradation and synthesis chemically similar?

Yes

Are fatty acids synthesized and degraded by different pathways?

Yes

Synthesis occurs in?

The cytoplasm

Synthesis occurs in the cytoplasm, whereas degradation occurs in?

The mitochondrial matrix

Intermediates in synthesis are covalently linked to

The sulfhydryl gropus of an acyl carrier protein

Wheras, intermeidates in degradation are covalently attached to the

Sulfhydryl group of coenzyme A

The activated donor of 2 carbon units in synthesis is

Malonyl ACP, whereas degradation releases acetyl CoA

The reductant is synthesis is NADPH, whereas the oxidants in degradation are

NAD+ and FAD

For Fatty acid synthesis, citrate carries acetyl groups from

mitochondria to the cytoplasm

Are mitochondria readily permeable to acetyl CoA

No