CH 21 BCH

Fatty acids are activated for β-oxidation by the transfer of

AMP from ATP

Allcarbon atoms of cholesterol (and steroids) derived from ____

Acetyl-CoA

Know the enzyme that catalyzes fatty acid activation

Acyl-CoA synthetase

Where in the cell does β-oxidation occur?

mitochondrial matrix

where are enzymes of beta oxidation located

mitochondrial matrix

HDL

transports cholesterol back to liver for degradation to bile acids

LDL function

transports cholesterol from liver to cells

main storage form for fatty acids

triacylglycerol

T/F The use of cyclic AMP to mobilize fatty acids from adipose tissue is analogous to cyclic AMP's role in mobilization of sugars from glycogen in the liver.

true - cyclic amp is in response to low blood sugar

What is the net yield of ATP when palmitate (C16) is completely oxidized via the β-oxidation pathway? Express answer as whole number.

8 acetyl-CoA X 10 ATP each = 80 7 rounds of oxidation x 4 ATP each = 28 Cost of activating FA chain = -2 Net = 80 + 28 -2 = 106

energy yield from oxidation of stearic acid

8 rounds of b oxidation 8 x 4 = 32 9 moles of acetyl CoA 9 x 10 = 90 90 + 32 -2 (activation) = 120 per 1 glucose 32 ATP/6 carbon = 5.33

The first three reactions of the β-oxidation cycle of fatty acids produce

1 NADH and 1 FADH2 - later converted to ATP

Know the energy yield associated with b-oxidation (how many ATP/round)

1 mole FADH2 = 1.5 atp 1 mole nadh = 2.5 atp 1 mole of f.a. = 4 atp total number of rounds needed to break down f.a. = 1/2 the amount of carbon bond 8 rounds of b oxidation = 32 atp - amount of acetyl coated rounds - 1

Know the two types of ketone bodies- Which is used in most tissues what is a byproduct

1. Acetone,b-hydroxybutyrate 2. acetoacetate • Acetoacetate used as fuel in most tissues and organs - Know that acetone is a non-enzymatic by-product

Know the pathway for palmitate synthesis Why is Co2 added?????

1. Acetyl first transferred to ACP and then to Cys thiol- releases CO2 2. Malonyl transferred to ACP 3. Condensation reaction with release of CO2 reduce, dehydrate, reduce

Cholesterol biosynthesis

1. Begins with condensation of 3 molecules of acetyl-CoA to form HMG-CoA 2. Formation of mevalonate completed by reduction of thioester • Gives 1°alcohol • Main control point in cholesterol synthesis • Target of Lipitor®and other drugs 3. Isopentenyl pyrophosphate producedafter: • Phosphorylation of the 1° alcohol of mevalonate • Concerted decarboxylation and β-elimination of phosphate ion

Acetyl-CoA Carboxylase Reaction steps

1. Bicarbonate first activated by phosphorylation from ATP 2. Biotin cofactor performs nucleophilic attack- Becomes carboxylated 3. Nucleophilic attack by acetyl-CoA carbanion results in transcarboxylation: Formation of malonyl-CoA

b-Oxidation- oxidation step 4

1. Cleavage of b-ketoacyl-CoA, catalyzed by thiolase a. CoA required b. produces acetyl-CoA and acyl- CoA c. 2 carbons shorter than og molecule

Know the general steps in the synthesis of triacylglycerols

1. Glycerol 3 phosphate made from glycerol or dihydroxyacetone 2. Glycerol-3-phosphate acylated twice to from phosphatidate 3. Dephosphorylated and acylatedto form TAG

Know that there are hormone-dependent lipases and how they function (in general)

1. Hormone binds receptor 2. Stimulates PKA pathway 3. Results in lipolysis 4. Fatty acids released for oxidation for energy

Know what occurs in catabolizing odd-chain FA

1. Last b-oxidation cycle of these fatty acids gives propionyl-CoA 2. Converted to succinyl-CoA 3. Then enters citric acid cycle

b-Oxidation- oxidation step 1 - process and cofactors

1. OXIDATION: acyl-CoA oxidized to a, b unsaturated acyl-CoA a. catalyzed by an FAD dependent acyl-CoA dehydrogenase

Know the cost of activation in ATP equivalents in f.a. transport

2

How many acetyl-CoA molecules are involved in forming HMG-CoA during ketogenesis?

3

The reactions involved in β-oxidation of fatty acids include the following: 1) Cleavage of acetyl-CoA from the fatty acid 2) Hydration of a double bond 3) Formation of a C−C double bond 4) Oxidation of an alcohol The correct order of these reactions is:

3 → 2 → 4 → 1 process is a spiral. in each cycle the molecules get shorter

how many molecules of atp does 1 glucose produce

32 atp 5.33 per carbon atom

Acylglycerols

esters of glycerol and fatty acids

Other than their use in nucleic acid synthesis, which energy source is used uniquely for the synthesis of lipids?

CTP

Oxidation of Monounsaturated Fatty Acids

Cis-transisomerization needed to convert monounsaturated fatty acids to acetyl-CoA - beta-oxidation produces a trans fatty acid in the first step

Pathway of Palmitate Synthesis- cost per round

Costs 2 NADPH (5 ATP)

where does fatty acid activation take place and why

Esterification takes place in cytosol, fatty acid oxidation occurs in mitochondrial matrix because Fatty acid not water-soluble

main control of cholesterol synthesis

HMG CoA reductate

Know general way in which phosphatidylserine formed

active head group attack to back bone activate backbone and attack head group o Exchange of ethanolamine head group for serine

Know the two types of enzymes that function in the catabolism of lipids and be able to differentiate them

Lipases and phospholipases

Reduction reactions during fatty acid synthesis utilize

NADPH - overall reductive - so we need a reductive cofactor NADPH vs NADH they carry the same thing NADPH involved = anabolic NADH = catabolic

Know how and why activated fatty acids are transported into the mitochondrial matrix

R is long hydrocarbon and has negative charge water insoluble is why it needs to be soluble- attaches co enzyme A now it can go into mito membrane and transport with CPT1 to carnitine molecule to matrix

Know the general result of fatty acid oxidation

Release of 2-carbon units from fatty acid chains

Products of ketogenesis

acetoacetate to acetone or beta hydroxybutarate brain can only use acetone or beta hydroxybutarate

The oxidation of an unsaturated fatty acid leads to the production of fewer ATPs than a saturated fatty acid with the same number of carbons because ____

The double bond results in the bypassing of the first oxidation step of the pathway, thereby eliminating one FADH2 product - LESS ENERGY PRODUCED - double bond generated in first step so we can skip that normal first step so less ATP/ 1 fewer FADH2

Fatty Acid Biosynthesis · Know the enzyme name and where this occurs

The enzyme system that catalyzes the synthesis of saturated long-chain fatty acids from acetyl CoA, malonyl CoA, and NADPH is called the fatty acid synthase. - takes place in the cytosol

Know the energy yield associated with catabolism of acetyl-CoA in TCA cycle (ATP/acetyl-CoA)

acetyl - coat released with each cycle in b oxidation 3 mole nadh= 7.5 atp 1 mole fadh2 = 1.5 atp 1 mole gtp = 1 atp total 10 number of rounds needed to break down f.a. = 1/2 the amount of carbon bond 9 moles of acetyl co-a = 90 Atp

purpose of lipoproteins

binds to surface on receptor on cell and transport it makes it more hydrophilic

The carrier molecule which transports fatty acids through the inner mitochondrial membrane is Group of answer choices

carnitine

A deficiency of carnitine results in muscle cramps, which are exacerbated by fasting or exercise. Give a biochemical explanation for the muscle cramping, and explain why cramping increases during fasting and exercise.

carnitine is carrier molecule of fatty acid- used for energy via beta oxidation muscles experience a lack of energy/ ATP for this carrier molecule

LDL particle

contains many cholesteryl esters - protein makes it soluble - binding to cell receptor

Fatty acid biosynthesis/ Acetyl-CoA Carboxylase Reaction occurs in the

cytosol

Where in the cell does fatty acid synthesis occur?

cytosol but beta oxidation is mitochondria- they are competing pathways

The addition of two-carbon units to a growing fatty acid chain is directly driven by

decarboxylation of malonyl-CoA - first step

energy yield from oxidation of f.a.

each cycle of b- oxidation 1 mole of FADH2 1 mole NADH total: 4 ATP acetyl coA enters citric acid 3 mole NADH 1 mole FADH2 1 mole GTP Total: 10 ATP 8 rounds of b oxidation 8 x 4 = 32 9 moles of acetyl CoA 9 x 10 = 90 90 + 32 -2 (activation) = 120

Know the process of fatty acid activation and its purpose

fatty acid oxidation begins with activation - the formation of a thioester bond between a fatty acid and acetyl-CoA The activated form of the fatty acid is an acyl-CoA, the exact nature of which depends on the nature of the fatty acid itself. The activated fatty acid must be transported into the mitochondrion so that the rest of the oxidation process can proceed.

FADH2 vs NADH in complex 2

fewer ATP produced with FADH2- lower P/O ratio

Ketogenesis occurs when _____.

glucose availability is low

fatty acid synthesis produces ____

palmitate

A key intermediate in the catabolism of fatty acids with uneven numbers of carbon atoms is

propinyl- CoA - active it and add CO2 group - becomes succinyl coa in order to enter the citric acid cycle

Role of cholesterol in heart disease

regular strenuous exercise increases HDL levels and decrease probability of heart disease - smoking reduced level of HDL and highly correlated with heart disease

The processing of one molecule of stearic acid (18 carbons) by β-oxidation

requires 8 cycles of β-oxidation and produces 9 molecules of acetyl-CoA. Carbons /2 = number of acetyl coA # of rounds: # of acetyl CoA-1, so 8 cycles 10 ATP per acetyl coa 4 ATP per round -2 ATP cost

Which of the following is not an advantage of fatty acids as a form of energy storage?

storage of fats in muscle tissue make it readily available for use during activity true facts - more highly reduced carbons than carbohydrates - hydrophobic- tightly packed into tissues - contain more energy than sugar

When glucose is unavailable, the liver begins to break down fatty acids to supply the rest of the body with metabolic fuel. Explain why fatty acid-derived acetyl-CoA is not catabolized by the citric acid cycle but is instead diverted to ketogenesis when no glucose is available.

when glucose are unavailable, your body uses ketone bodies instead. in the absence of glucose, acetyl-CoA cannot enter the citric acid cycle due to insufficient oxaloacetate, a substrate for the first step. When carbohydrate concentrations drop, any available oxaloacetate is diverted to gluconeogenesis to produce the glucose necessary for red blood cell and brain function. If acetyl-CoA cannot enter the citric acid cycle (and acetyl-CoA cannot be converted to pyruvate in mammals), it is converted to ketone bodies.

Oxidation Pathway for Polyunsaturated Fatty Acids

§ Double bonds may need to be reduced due to position in chain § Energy cost in NADPH oxidation - low energy yield

What is processed in ketogenesis?

• 3 molecules of actetyl-CoA condensed to HMG-CoA

Know the general synthesis of sphingolipids

• Biosynthesis requires palmitoyl-CoA and serine • Acylation of amino group backbone of sphingosine results in ceramide and amide bond

Fatty Acid Biosynthesis o Where does the substrate come from and why? o How is carried from the matrix to the cytosol?

• Biotin - carrier of carboxyl group and important cofactor in reaction

Know the enzymes that participate in the process of f.a. transport and what they do

• Carnitine acyl transferase- Transfers fatty acyl group to carnitine bc they can not diffuse on their own Carnitine palmitoyl transferase(CPT-I) · transfer long-chain fatty acyl groups from Coenzyme A to carnitine Carnitine palmitoyl transferase(CPT-II) · it functions to transfer long-chain fatty acyl groups from carnitine to Coenzyme A where beta oxidation will occur

Know the general name for enzymes that lengthen fatty acid chain and where this occurs

• Chains lengthened by elongases • Occurs in mitochondria and ER

Where in the cell does β-oxidation occur?Know the general name for enzymes that unsaturate chain in f.a. metabolism and where this occurs

• Double bonds introduced by desaturases • In ER

B-oxidation (hydration) step 2

• Hydration of unsaturated acyl-CoA to b-hydroxyacyl-CoA • Catalyzed by enoyl-CoA hydratase

Phosphoacylglycerol

• Key component of biological membranes • Phospholipases may have multiple sites of action • May participate in signaling pathways

Know that there are essential fatty acids and why (don't need to know specific f.a.)

• Linoleate, linolenate • Must be in diet • Precursors of other lipids

Triacylglycerol

• Main storage form of chemical energy for most organisms • Carbon chains in highly reduced form • Energy yield per gram of fatty acid greater than per gram of carbohydrate

b-Oxidation- oxidation step 3

• Oxidation reaction, catalyzed by b-hydroxyacyl-CoA dehydrogenase • NAD+-dependent enzyme • Generate NADH

what does Acetyl-CoA Carboxylase Reaction produce- why is this significant to fatty acid biosynthesis

• Produces key intermediate, malonyl-CoA- !!starting compound for fatty acid synthesis!!

required cofactors for Acetyl-CoA Carboxylase Reaction

• Requires Mn2+, biotin, and ATP

Understand when ketogenesis is active and why

•Active when amount of acetyl-CoA excessive compared to amount of oxaloacetate available • Leads to production of large amount of acetyl-CoA by b-oxidation - brain can't use f.a. for energy so it needs to be converted to ketone bodies

fatty acid biosynthesis main cofactor how is it similar to CoA

•Main cofactor is acyl carrier protein (ACP) •Similar to coenzyme A - both carry thiol