Biochem: EXAM 2 (Ch.23) Fatty Acid & Eicosanoid Synthesis

Slides from textbook cards and edited with slideshow notes

Fatty acids are synthesized by an ______________, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the CYTOSOL.

extramitochondrial system

In most mammals, __________ is the primary substrate for lipogenesis

Glucose

______________ in phospholipids of the cell membrane are important in maintaining membrane fluidity.

Unsaturated fatty acid

______________ mediate inflammation, pain, and induce sleep and also regulate blood coagulation and reproduction.

Prostaglandins

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as __________ and _________ act by inhibiting _______ synthesis.

aspirin and ibuprofen, prostaglandin

_______________ have muscle contractant and chemotactic properties (allergic and hypersensitivity reaction) and are important in allergic reactions and inflammation.

Leukotrienes

THE MAIN PATHWAY FOR THE SYNTHESIS OF FATTY ACIDS (LIPOGENESIS) OCCURS IN THE ______________.

CYTOSOL

What are the cofactor requirements for Fatty Acid synthesis/ Lipogenesis? (4)

NADPH,ATP,Mn2, Biotin

_____________ is the immediate substrate, and ____________ is the end product of fatty acid synthesis

Acetyl-CoA,free palmitate

Production of ____________ is the Initial & Controlling Step in Fatty acid Synthesis

Malonyl-Coa

What is required for the initial reaction for the carboxylation of acetyl-CoA to malonyl-CoA (2)? What enzyme does this?

CO2 (in the form of bicarbonate) and ATP, acetyl-CoA carboxylase

This enzyme has a major role in the regulation of fatty acid synthesis.

Acetyl-CoA carboxylase

The _______________ Is a homodimer of Two polypeptide Chains Containing 7 Enzymes

Fatty acid Synthase Complex

The individual enzymes required for fatty acid synthesis are linked in this multienzyme polypeptide complex that incorporates the _______________, which has a similar function to CoA in the β-oxidation pathway. It contains the vitamin ____________ in the form of 4′-phosphopantetheine.

acyl carrier protein (ACP),pantothenic acid

What are the advantages to using a multi enzyme functional unit like in the case of the fatty acid synthase complex? (2)

compartmentalization of the processes within the cell without the need for permeability barriers and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene

The 3-ketoacyl group is reduced, dehydrated, and reduced again (reactions 3-5) to form the corresponding _.

satacyl

When does the sequence of reaction in the fatty acid synthesis complex stop repeating?

When palmitic acid (16:0) is formed

The free palmitate made at the end of FA synthesis must be activated to ___ before it can proceed via any other metabolic pathway

acyl-CoA

The acetyl-CoA used as a primer forms carbon atoms ____ and ____ of palmitate.

15 and 16

The addition of all the subsequent C2 units to elongate palmitic acid is done via __

malonyl-CoA

The Main Source of NADPH for Lipogenesis Is the _.

pentose phosphate pathway

is involved as a donor of reducing equivalents in both the reduction of the 3-ketoacyl and of the 2,3-unsaturated acyl derivatives.

NADPH

The oxidative reactions of the pentose phosphate pathway are the chief source of the ___ required for the reductive synthesis of fatty acids.

hydrogen

Significantly, tissues specializing in active _ —ie, liver, adipose tissue, and the lactating mammary gland— also possess an active pentose phosphate pathway.

lipogenesis

True or False: Both the PPP and lipogenesis pathways are found in the cytosol of the cell; so, there are no membranes or permeability barriers against the transfer of NADPH.

True

"malic enzyme”

isocitrate dehydrogenase

_ Is the principal Building Block of Fatty acids

acetyl-Coa

What is formed from glucose via the oxidation of pyruvate in the matrix of the mitochondria.

Acetyl-CoA

Acetyl-CoA cannot freely pass through the mitochondrial membranes, its transport into the cytosol, the principal site of fatty acid synthesis, requires a special mechanism involving __.

citrate

After condensation of acetyl-CoA with oxaloacetate in the citric acid cycle within mitochondria, the citrate produced can be translocated into the extramitochondrial compartment via the , where in the presence of CoA and ATP, it undergoes cleavage to acetyl-CoA and oxaloacetate catalyzed by _, which increases in activity in the well-fed state.

ATP-citrate lyase

Note that the malate shuttle in the mitochondrial membrane that moves Acetyl-CoA out of the mitochondria requires ___ to exchange with citrate.

malate

Elongation of Fatty acid Chains Occurs in the _.

Endoplasmic reticulum

What converts surplus glucose and intermediates such as pyruvate, lactate, and acetyl-CoA to fat, assisting the anabolic phase of this feeding cycle.

Lipogenesis

The nutritional state of the organism is the main factor regulating the rate of ___.

lipogenesis

There is a _____ relationship between hepatic lipogenesis and the concentration of serum-free fatty acids.

inverse

Lipogenesis is increased when __ is fed instead of glucose because fructose bypasses the phosphofructokinase control point in glycolysis and floods the lipogenic pathway.

sucrose

_ Is the Most Important Enzyme in the regulation of Lipogenesis

acetyl-Coa Carboxylase

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by ____, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl CoA. What is it inhibited by? (3)

citrate, inhibited by glucagon, epinephrine, and long-chain fatty-acyl CoAs.

Acetyl-CoA carboxylase is also regulated by hormones such as , _ (3)and via changes in its phosphorylation state.

glucagon, epinephrine, and insulin

Acyl-CoA causes an inhibition of ____ , which regulates the availability of acetyl-CoA for lipogenesis.

pyruvate dehydrogenase

_ stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity.

Insulin

______ increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol-3-phosphate for triacylglycerol synthesis via esterification of the newly formed fatty acids and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue, but not in liver.

Insulin

____ inhibits lipolysis in adipose tissue and reducing the concentration of plasma-free fatty acids and, therefore, long-chain acyl-CoA, which are inhibitors of lipogenesis.

Insulin

Other C20, C22, and C24 polyenoic fatty acids may be derived from ____ (3) by chain elongation.

oleic, linoleic, and α-linolenic acids

_ and _ are not essential in the diet because the tissues can introduce a double bond at the Δ9 position of a saturated fatty acid.

Palmitoleic and oleic acids

_ and _ are the only fatty acids known to be essential for the complete nutrition of many species of animals, including humans, and are termed the nutritionally essential fatty acids.

Linoleic and α linolenic acids

In most mammals, what fatty acids can be formed from linoleic acid.

arachidonic acid

True or False: Double bonds can be introduced at the Δ4, Δ5, Δ6, and Δ9 positions in most animals, but never beyond the Δ9 position.

True

In contrast, plants are able to synthesize the nutritionally essential fatty acids by introducing double bonds at the Δ_ and Δ_ positions.

12 and 15

MONOUNSATURATED FATTY ACIDS ARE SYNTHESIZED BY A _.

Δ9 DESATURASE SYSTEM

Several tissues including the ____ are considered to be responsible for the formation of nonessential monounsaturated fatty acids from saturated fatty acids.

liver

The first double bond introduced into a saturated fatty acid is nearly always in the ____position and are always ____ double bonds

delta 9, cis

An enzyme system__________ in the smooth endoplasmic reticulum catalyzes the conversion of palmitoyl-CoA or stearoyl-CoA to palmitoleoyl-CoA or oleoyl-CoA and is the primary way we synthesize MUFA

Δ9 desaturase

What is the pathway to convert linoleic acid (18:2 delta 8,12) to arachidonic acid (20:4 delta 5,8,11,14)

First, use delta 6 FA desaturase to get gamma linolenic acid (18:3 delta 6,9,12) and then used FA elongase to get 20:3 delta 8,11,14 then use delta 5 FA desaturase to get arachidonic acid

____ are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation and they also have various other functions that are less well defined.

Essential fatty acids

Arachidonic acid is present in what percentage of membranes and accounts for what percentage of the fatty acids in phospholipids respectively.

5% to 15%

_ is particularly needed for development of the brain and retina and is supplied via the placenta and milk.

DHA

What is needed for ethanol metabolism?

NAD and alcohol dehydrogenase

What activates the fatty acid synthase complex?

insulin

What is requires for fatty acid synthase complex? (3)

acetylCoA, NADPH, and ATP

What is ATP citrate lyase a part of?

The malate shuttle to get Acetyl-CoA out of the mitochondria to do fatty acid synthesis

What does Acetyl CoA carboxylase and Biotin do? What does it use?

convert acetylene CoA plus CO2 into Malonyl CoA using ATP

What forms when acetyl CoA and malonyl CoA join in the FA Synthase complex?

ketoacyl group

What is the desaturation process for fatty acids?

the removal of 2Hs to insert a double bond

Where are fatty acid elongases found?

Smooth endoplasmic reticulum

What are the FA desaturates? (3) What are they always?

delta 9, delta 6, and delta 5, they are always cis

Humans are incapable of desaturating a fatty acid beyond carbon __

10

Desaturation can be done with any FA usually at least ____ carbons or longer?

14

What does desaturation enzymes require? (2)

NADH+ and O2

Say true

true

What forms DHA?

EPA

What are omega-3 and omega-6 fatty acids essential for?

eicosanoid synthesis, brain development, retina development, sperm development

What are eicosanoids synthesized from? What are they?

20 carbon omega-3 and omega-6 PUFAs; they are hormones that act locally to elicit [owerful biochemical effects on tissues

What enzyme removes FA from position 2 to synthesize eicodanoids?

Phospholipase A2

What are the 4 major eicosanoid classes?

prostaglandins, thromboxane, leukotrienes, lipoxins

Leukotrienes from arachindoic are _______ while Lipoxins from arachidonic are ________

pro inflammatory, anti-proinflammatory

Is PGI2 pro- or anti-inflammatory, What about PGI3?

anti-inflammatory, pro-infammatory

Is TXA2 pro-or anti-inflammatory? What about TXA3

pro-inflammatory, anti-inflammatory

What produces the majority of leukotrines?

5-lipoxygenase

What does Acyl CoA synthase always require? (2)

CoA and ATP

What does the enzyme Acyl CoA do to palmitic acid in terms of the synthesis of MUFAs and sphingolipid synthesis?

It activates palmitic acid into Palmitoyl-CoA which can be used in metabolic pathways

What does 𝚫𝟓-desaturase (FADS1) do?

It acts in the omega-3 and omega-6 pathways, such as converting dihomo-γ-linolenic acid (DGLA) to arachidonic acid.

What does 𝚫𝟗-desaturase (SCD1) do? Why is it important?

It converts stearic acid to oleic acid and is the primary enzyme for producing monounsaturated fatty acids.

What does 𝚫𝟔-desaturase (FADS2) do? (2)

It converts linoleic acid (LA) to gamma-linolenic acid (GLA) and α-linolenic acid (ALA) to stearidonic acid

What can linolenic acid synthesize using the delta 6 system? What can alpha-linolenic acid synthesize as a delta 3?

Arachidonic acid, EPA which can become DHA

Where is EPA and other long chain fatty acids beta oxidized?

peroxisomes