mod 1 fatty acid metabolism

how does peroxisome oxidation differ from β oxidation?

in the initial dehydrogenation reaction. Acyl CoA dehydrogenase *transfers electrons from the substrate to FADH2 and then to O2 to yield H2O2*. Catalase to degrade H2O2 into water and O2.

ATP-citrate lyase is stimulated by

insulin

Odd-numbered double bonds are handled by the ______, and even-numbered ones by the ______

isomerase isomerase and reductase

When additional steps are required, the first 3 cycles are the same, but then ______ *(odd number of x2 bonds)*

isomerase converts the double bond into a trans-Δ2 double bond.

propionyl CoA what is it considered? how is it oxidized? What is required for this? What enzyme does it use?

*Minor species.* • Oxidized in the same way as even number fatty acids, except that *propionyl CoA is converted to succinyl CoA that enters TCA cycle. * • This requires *vitamin B12 (cobalamin). * • Enzyme: *Propionyl CoA carboxylase* (a biotin enzyme).

in order to reach tissues, fatty acids *bind to ______* in ______ which ______

*albumin in blood*, which delivers them to tissues

Fatty acid synthesis starts with the ______

*carboxylation of acetyl CoA to malonyl CoA. * This irreversible reaction is the committed step in fatty acid synthesis

______ are formed from acetyl CoA when fat breakdown predominates aka when the body is breaking down fats b/c it's STARVING

ketone bodies

Abnormally high levels of ______ are present in the blood of untreated diabetics They can serve as ______ for some tissues

ketone bodies, which server as a major fuel for some tissues

triacylglycerol droplets coalesce to form __________

lipid droplets

In fatty acid rich diet ______ and ______ are still capable of synthesizing fatty acids.

liver and adipose tissue

Inappropriate fatty acid synthesis in the liver of alcoholics contributes to

liver failure

Acetyl CoA is transferred from ______ to ______ what does this do?

mitochondria to the cytoplasm. the reducing potential of NADH is concomitantly converted into that of NADPH by this series of reactions.

oxidation of fatty acid occurs in the ______

mitochondrial matrix

Lipids solubility inw ater? exit the stomach as an ______ 1 The particles are coated with ______ 2 what binds lipase to the particle?

not soluble in water exit stomach an an emulsion with a triacylglycerol core surrounded by cholesterol and cholesterol esters. 1 particle coated with *bile acids* from cholesterol in the liver, previously secreted by the gallbladder 2 *Colipase* (from pancreas) bind lipase to the particle (basically a triacylglycerol) to permit lipid degradation into *fatty acids and monoacylglycerols*

In fasting or diabetes, ______ is consumed to form glucose by the gluconeogenic pathway and hence is ______ Under these conditions, acetyl CoA is diverted to the formation of ______

oxaloacetate unavailable for condensation with acetyl CoA. *acetoacetate and* d-3-hydroxybutyrate referred to as *ketone bodies*.

The shortened acyl CoA then undergoes another cycle of ______, starting with ______

oxidation the reaction catalyzed by acyl CoA (just a repeat of acyl CoA degradation, just keeps making more Acetyl CoA until the hydrocarbon chain is too short to work with)

degradation fo fatty acid is a ______ process that ______

oxidative process that converts a fatty acid into a set of activated acetyl units (acetyl CoA) to go to the citric acid cycle

The major product of the fatty acid synthase is ______

palmitate

LIPASES

pancreatic enzyme that degrages triacylglycerols to free fatty acids and monoacylglycerol

The Elongation and Unsaturation of Fatty Acids Are Accomplished by

accessory enzyme systems

fatty acid components of biological membranes building blocks for

phospholipids glycolipids amphipathic molecules (polar/nonpolar parts)

Acetyl CoA carboxylase is switched off by ______and activated by ______

phosphorylation dephosphorylation

*Eicosanoid hormones* are derived from

polyunsaturated fatty acids

Odd-chain fatty acids yield______ in the final thiolysis (cleavage) step

propionyl CoA

One molecule of NADPH is generated for each molecule of ______

acetyl CoA that is transferred from mitochondria to the cytoplasm.

precursor for virtually all fatty acids is ______ which is the end product of ______

acetyl CoA, which is the end product of fatty acid degradation

Citrate carries ______ from ______ to ______

acetyl groups from inner mitochondrial membrane to the cytoplasm for fatty acid synthesis

Intermediates in fatty acid synthesis are attached to an

acyl carrier protein (ACP)

major site of triacylglycerol

adipose cells

Fatty acids separate from the ______ in the blood stream and diffuse across the cell membrane with the assistance of ______ in the cell, they are shuttled by ______

albumin transport proteins fatty-acid-binding-proteins

Acetyl CoA cannot be converted into ______ or ______ in animals.

pyruvate or oxaloacetate

AMP-activated protein kinase (AMPK) converts the ______ It's essentially a ______ Activated/inhibited by

carboxylase into an inactive form by modifying *three serine residues*. AMPK is essentially a fuel gauge; it is activated by AMP and inhibited by ATP.

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

cellular organelles called peroxisomes.

The carboxylase is also allosterically stimulated by ______, which there are high levels of when ______ (from above) also facilitates ______

citrate. The level of citrate is high when both acetyl CoA and ATP are abundant, signifying that raw materials and energy are available for fatty acid synthesis. Citrate facilitates the polymerization of the inactive dimers into active filaments

Fatty acid synthesis consists of a series of ______,______,______,______ reactions

condensation, reduction, dehydration, and reduction reactions

Fatty acids are synthesized in the ______ , whereas acetyl CoA is formed from ______ Hence, acetyle CoA must be transferred from______

cytoplasm pyruvate in mitochondria Hence, acetyl CoA must be transferred from mitochondria to the cytoplasm.

Fatty acid oxidation in peroxisomes where does it end serves to ______

halts at octanoyl CoA serves to shorten very long chains (C26) to make them better substrates of β oxidation in mitochondria.

The degradation of palmitoyl CoA (C16-acyl CoA) requires how many cycles?

seven reaction cycles

triacylglycerol can provide energy for ______ (time span)

several weeks

Polyunsaturated fatty acids are important precursors for

signal molecules

In eukaryotes, longer fatty acids are formed by elongation reactions catalyzed by enzymes on the ______ These reactions add ______ what is the donor/what drives it?

*cytoplasmic face* of the endoplasmic reticulum membrane. These reactions *add two-carbon units* sequentially to the carboxyl ends of *both saturated and unsaturated fatty acyl CoA substrates.* *Malonyl CoA* is the two-carbon *donor* in the elongation of fatty acyl CoAs. Again, condensation is *driven by the decarboxylation of malonyl CoA.*

When there is an absence of insulin, The liver degrades the fatty acids by ______ but cannot what is then formed?

*β oxidation* but *cannot process the acetyl CoA*, because of a *lack of glucose-derived oxaloacetate (OAA).* • Excess ketone bodies are formed and released into the blood.

process to get from fatty acids to oxidized acyl carnitine (4)

1- FAs are activated on the outer mito membrane 2- They are conjugated to *carnitine (an alcohol zwitterion)* 3- *Acyl carnitine is shuttled* across the inner mitochondrial membrane by *translocase* (membrane bound protein) 4- Acyl carnitine is then oxidized in the mito matrix, *Acyl CoA* stays in matrix while *Carnitine* travels back to the cytoplasmic side

Mobilization of triacylglycerols processes to turn it into base components

1- hormones activate PKA via cAMP cascade 2- PKA phosphorylates perilipin which releases ATGL 3- ATGL converts TAG into DAG 4- lipase is used to form FA and MAG from DAG 5- MAG lipase complete the mobilization *First: cAMP>PKA>Perilipin>ATGL (TAG to DAG+FA)* *Next: Lipase (DAG to MAG+FA)* *Last: MAG Lipase (MAG to FA+glycerol)* Makes 3 FAs + glycerol using 3 H2Os

Three stages of fatty acids processing to use as fuel (from TAGs to how it becomes energy for a cell) *What happens to TAGs and the FAs that come from it?*

1- lipids are mobilized and triacylglycerols are degraded to fatty acids and glycerol and released from the adipose tissue, then transported to the energy requiring tissues 2- FA are transported to mitochondria 3- FA are broken down to Acetyl CoA for TCA cycle

Glycerol formed by lipolysis is absorbed by the liver, where it is ______(3) thus in the liver, glycerol can end up as ______ or ______

1- phosphorylated 2- oxidized to DHAP 3- then isomerized to GAP (used in gly and GNG) thus in the liver, glycerol can end up as *pyruvate or glucose*

fatty acid major roles

1-fuel molecules 2- building blocks 3- targeting proteins to membrane locations 4- hormones and intracellular messengers

4 steps of fatty acid degradation what if the fatty acid ends with an even number of carbons?

1. An activated fatty acid is *oxidized* to introduce a double bond. 2. The double bond is *hydrated* to introduce a hydroxyl group. 3. The alcohol is *oxidized* to a ketone. 4. 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 number of carbon atoms and is saturated, the process repeats until it's all converted into acetyl CoA units *synthesis is essentially just the reverse

Fatty acids synthesis and degradation take place by different pathways Step 1: where do they take place?

1. Synthesis in the cytoplasm, but degradation, in the mitochondrial matrix.

The complete oxidation of palmitate yields

106 ATP

Long Fatty acid chains containing from ______ are oxidized by the ______.

12 to 18 carbon atoms long chain acyl CoA dehydrogenase

Fatty acids synthesis and degradation take place by different pathways Step 2: What do the intermediates do?

2. Intermediates in fatty acid synthesis covalently *linked to the sulfhydryl groups of an acyl carrier protein (ACP)*, but intermediates in fatty acid breakdown are *covalently attached to the sulfhydryl group of CoA*

Fatty acids synthesis and degradation take place by different pathways Step 3: Enzymes

3. The enzymes of fatty acid synthesis in higher organisms are joined in a single polypeptide chain called *fatty acid synthase, * but the degradative enzymes are not linked covalently.

3 The final digestion products are carried in ______ to ______

3. micelles to the intestinal epithelium where they are transported across the plasma membrane

The short-chain acyl CoA dehydrogenase acts only on ______ In contrast, ______, ______, and ______ act on fatty acid molecules of almost any length.

4- and 6-carbon fatty acid chains. β-ketothiolase, hydroxyacyl dehydrogenase enoyl CoA hydratase

4 Triacylglycerols are resynthesized and packaged with ______ and ______ to form ______ 5 ______ is then released into ______ and then to the ______

4. *Triacylglycerols are resynthesized* and packaged with other lipids and apolipoprotein B-48 to form *CHYLOMICRONS*, which are then released into the lymph system 5. Chylomicrons are *released* into the *lymph* system and then into the *blood*.

Fatty acids synthesis and degradation take place by different pathways Step 4: how is the chain elongated? (what is donor/drive by what)

4. fatty acid chain is elongated by *addition of 2-C units from acetyl CoA*. The *activated donor is malonyl ACP*. Elongation is *driven by release of CO2*

Fatty acids synthesis and degradation take place by different pathways Step 5: reductants and oxidants in each

5, The *reductant* in fatty acid synthesis is *NADPH*, whereas the *oxidants* in fatty acid degradation are *NAD+ and FAD*

Fatty acids synthesis and degradation take place by different pathways Step 6: What isomeric form do they use?

6. *d form* is used in synthesis. isomeric form of the hydroxyacyl intermediate in degradation is *form L*

6 At adipose tissue and muscle, chylomicrons bind to membrane bound lipases, and ______ 7 8

6. triacylglycerols are once again degraded into free fatty acids and monoacylglycerol for transport into the tissue. 7. Triacylglycerols are then resynthesized inside the cell and stored. 8. In muscles provide energy

The synthesis of palmitate requires End products?

8 molecules of acetyl CoA, 14 molecules of NADPH, and 7 molecules of ATP Products: palmitate 14 NADP+ 8CoA 6H2O 7ADP 7Pi

what is generated in each round of fatty acid oxidation

Acetyl CoA NADH FADH2

______ carries long-chain activated fatty acids into the mitochondrial matrix

Carnitine

Acetyl CoA Carboxylase Plays a Key Role in Controlling

Fatty Acid Metabolism

Fatty Acids Are Synthesized by ______ (enzyme)

Fatty Acid Synthase

Ketone bodies major production site: Transported by ______ to ______ Is the normal fuel of ______ In prolonged starvation, it meets ______% of the brains fuel needs. High levels can be ______ b/c? pathway from TAGs in a fat cell to CO2 and water in another cell (during starvation/fasting)

Liver blood to heart and kidney respiration 75% life threateneing b/c it would drop your *blood pH very low* pathway: TAGs are degraded into glycerol and FA which enter blood stream and end in a liver cell in a liver cell, 1- glycerol is used to make glucose which goes to the blood and enters another cell and 2-FA is used to my acetyl CoA > Ketone bodies in a mito matrix, which then goes into the bloodstream and enters another cell in the other cell (probably brain), ketone bodies > acetyl CoA [TCA} > CO2 and H2O

Fatty acid synthesis requires other pathways (3) to produce:

PPP: NADPH Glycolysis/TCA: Citrate (to form Acetyl CoA and Oxaloacetate *via GNG*) GNG: NADPH

fatty acids are stored as ______ which are made of (2) ______ in ______ tissue what happens to them to meet energy needs?

Stored as *triacylglycerols* which are *uncharged esters of fatty acids with glycerol* in *adipose tissue* they are *oxidized* to meet energy needs

what requires additional steps for degradation what enzymes are required for the additional steps?

Unsaturated (aka has x2 bonds) and odd-chain fatty acids Fatty acids that *contain double bond* and an *odd number of Carbon atoms* require additional steps. Enzymes: *Isomerase* *Reductase*

fatty acid is made of ______

a long hydrocarbon chain and a terminal carboxylate group.

Arachidonate derived from 4 signal molecules

a *20:4 fatty acid derived from linoleate*, is the major precursor of several classes of *signal molecules: prostaglandins, prostacyclins, thromboxanes, and leukotrienes*

*The synthesis of malonyl CoA* is catalyzed by the ______ A group of the enzyme bonds to something else, how? What is then formed? Then ______ happens to form malonyl CoA

cytoplasmic enzyme acetyl CoA carboxylase 1, which contains a biotin prosthetic group The carboxyl group of biotin is covalently attached to the ϵ amino group of a *lysine residue.* A carboxybiotin intermediate is formed at the expense of the hydrolysis of a molecule of ATP. *The activated CO2 group in this intermediate is then transferred to acetyl CoA to form malonyl CoA*

Endoplasmic reticulum systems also introduce ______

double bonds into longchain acyl CoAs

what is fatty acid synthesis necessary during (2)?

embryonic development and during lactation in mammary glands.

triacylglycerols (define) made of/why do they have high energy?

esters derived from glycerol and three fatty acids - are highly concentrated stores of metabolic energy as they are *reduced* and *anhydrous* (lack water).

energy yield fat vs carb

fat = 9 card = 4

why are fats higher in energy vs carbs?

fats are more reduced than carbs/proteins they are also nonpolar and stored in a anhydrous form

In the absence of insulin, what is released and what does it affect?

fats are released from adipose tissue, and glucose cannot be absorbed by the liver or adipose tissue.

The medium-chain acyl CoA dehydrogenase oxidizes______

fatty acid chains having 14 to 4 carbons

What is the committed step of FA synthesis?

formation of malonyl CoA

Acetyl CoA carboxylase is controlled by the hormones effects of the hormones on FA synthesis?

glucagon, epinephrine, and insulin, which denote the overall energy status of the organism. *Insulin stimulates fatty acid synthesis* by *activating the carboxylase*, whereas *glucagon and epinephrine* have the *reverse effect.*

Animals cannot convert fatty acids into

glucose

Membrane-bound enzymes generate ______

unsaturated fatty acids

A saturated acyl CoA is degraded by a recurring sequence of *four *reactions: where does the oxidation take place? What is the pathway called?

• (1) Oxidation by (FAD), *Acyl CoA dehydrogenase* • (2) Hydration, *enoyl CoA hydratase* • (3) Oxidation by NAD+,* l-3-hydroxyacyl CoA dehydrogenase* • (4) Thiolysis by CoA (coenzyme A). *β-ketothiolase* Because oxidation takes place at the *β carbon atom*, this series of reactions is called the* β-oxidation pathway.*

where does the 106 ATP come from?

• 10.5 from the seven FADH2, • 17.5 from the seven NADH, and • 80 from the eight acetyl CoA molecules, this equals 108, but 2 ATP are consumed.