Ketone Bodies and Fatty Acid Biosynthesis

Low levels of glucose in the blood trigger the release of ____, which binds its receptor in the _____ membrane and stimulates the release of ____ ____ via a ____ ____ to produce _____, which activates ______

glucagon; adipose; adanyl cyclase; G protein; cAMP; PKA

Active PKA _______ the hormone-sensitive ____ and ____ molecules on the surface of the ____ ____.

phosphorylates; lipase; perilipin; lipid droplet

_______ of perilipin permits hormone sensitive _____ access to the surface of the lipid droplet, where it ______ _________ to _____ _____ _____

phosphorylation; lipase; hydrolyzes triacylglycerols; free fatty acids

____ ____ leave the adipocyte, bind serum ____, and are carried in the blood. They are released and enter a _____ via a specific ____ ____ ____

fatty acids; albumin; myocyte; fatty acid transporter

in the monocyte fatty acids are _____ to ____ and the energy of ____ is conserved in ______

oxidized; CO2; oxidation ATP

When the diet provides a ready source of carbohydrate as fuel, ____ _____ of ____ ____ in unnecessary and is therefore ____-regulated

beta oxidation; fatty acids; down

the first enzyme in the synthesis of fatty acids

acetyl-CoA carboxylase (ACC)

enzyme in fatty acid synthesis that limits the transport of fatty acids into the mitochondria

carnitine acyltransferase I

1 - phosphatase

2 - PKA

3 - Acetyl - CoA

4 - malonyl - CoA

5 - Fatty acyl-CoA

6 - Fatty acyl - carnatine

7 - Fatty acyl - carnatine

8 - CoASH

9 - Fatty acyl-CoA

10 - beta oxidation

11 - Acetyl -CoA

Fill in the diagram

insulin-dependent protein phosphatase _______ ACC, _____ it

dephosphorylates; activating

when blood glucose levels drop between meals, ____ release activates _______

glucagon; PKA

Because glucagon also triggers the _____ of fatty acids in adipose tissue, a supply of fatty acids begins arriving in the ____

mobilization; blood

In the liver during starvation, ______ is being consumed for ________. Therefore, there may not be enough for the _____ to function effectively. As a result, _____ produced by ______ builds up and cannot produce the normal amount of _____. So it is only produced from ____ and ______

oxaloacetate; gluconeogenesis; TCA; acetyl-CoA; beta oxidation; ATP: NADH; FADH2

because the last step of beta oxidation is ______, acetyl-CoA can be used to make ____ _____, a ___ soluble form of ____ energy. The liver lacks the enzyme to convert _____ into _____ ____ so the liver cant use ketone bodies, but _____ tissue can.

reversible; ketone bodies; water; lipid; acetoacetate; acetoacetyl CoA; extrahepatic

3 main ketone bodies

acetone, acetoacetate, D-B-hydroxybutyrate

high levels of ______ will lead to acidosis, which can be fatal

D-B-Hydroxybutyrate

ketone bodies are formed in the ____.

liver

since albumin cannot cross the blood brain barrier, the brain cannot use ____ ___ from the blood as an energy source. Under starvation conditions, the brain can adapt to use ____ or ______ when glucose is unavailable

fatty acids; acetoacetate; D-B-hydroxybutyrate

1 - thiolase

2 - CoA-SH

3 - HMG - CoA synthase

4 - Acetyl-CoA

5 - CoA-SH

6 - HMG - CoA lyase

7 - Acetyl -CoA

8 - acetoacetate decarboxylase

9 - CO2

10 - HADH + H+

11 - HAD+

12 - D-B-hydroxybutyrate dehydrogenase

fill in the chart

1) B-ketoacyl-CoA transferase

2) Succinyl-CoA

3) Succinate

extrahepatic tissues

Fill in the graph. In what kind of tissues does this take place?

ketone bodies are overproduced in _____ and during _____

diabetes; starvation

conditions that promote gluconeogenesis slow the _____ by drawing off _____ and enhance the conversion of ____ to _____. The released _____ allows continued ____ of fatty acids

TCA; oxaloacetate; acetyl-CoA; acetoacetate; coenzyme A; beta oxidation

the purpose of fatty acid biosynthesis is primarily the storage of excess fuel as _____. Synthesis occurs in the ____ utilizing _____ as compared to Beta oxidation, which occurs in the _____ using ______

TAG; cytoplasm; NADPH; mitochondria; NAD+

3 functional regions of Acetyl-CoA carboxylase

biotin carrier protein, biotin carboxylase, and transcarboxylase

Acetyl-CoA carboxylase rxn will produce a ____ carbon intermediate (_______) from a ___ carbon intermediate (_______). The added carbon will come off as _____ during chain elongation, causing the rxn to be pulled in the direction of ______

3; malonyl-CoA; 2; acetyl-CoA; CO2; biosynthesis

During fatty acid synthesis, the production of the first intermediate, malonyl-CoA, shuts down ______ by inhibiting _________ in the mitochondrial outer membrane. This control mechanism illustrates another advantage of segregating synthetic and degradative pathways in different cellular compartments.

beta-oxidation; carnitine acyltransferase I

the long carbon chains of fatty acids are assembled in a _____ ____ _____ _____

repeating four step sequence

label the type of reaction taking place

1 - condensation

2 - reduction

3 - dehydration

4 - reduction

The mammalian fatty acid synthase is a single large polypeptide that contains _________. It synthesizes ____ fatty acids simultaneously

all 7 enzymatic functions; 2

during palmitate, each new _____ ____becomes the _____ group while the ___ group is at the far end of the chain

malonyl CoA; carboxyl; acetyl

____ _____ _____ (___) is the attachment site for each malonyl-CoA and the growing fatty acid chain. It has the prosthetic group _________ with a terminal _____ group for acyl attachment

Acyl carrier protein (ACP); 4'-phosphopanthetheine; -SH

________-____-____ transferase transfers ____ group from ____ to ____ of a cysteine on beta-ketoacyl-ACP synthase (the first acyl group)

malonyl/acetyl-CoA-ACP; acetyl; CoA; -SH

______-____-____ transferase transfers the malonyl group from CoA to ACP

malonyl/acetyl-CoA-ACP

1 - condensation, B-ketoacyl-ACP synthase

2 - reduction of B-keto group, B-ketoacyl-ACP reductase

3 - dehydration, B-hydroxyacyl-ACP dehydratase

4 - reduction of double bond, enoyl-ACP reductase

5 - translocation of butyryl group to Cys on B-ketoacyl-ACP synthase, B-ketoacyl-ACP synthase

6 - recharging of ACP with another malonyl group , malonyl/acetyl-CoA-ACP transferase

determine the type of reaction happening and the domain of fatty acid synthase that does it.

condenses acyl and malonyl groups to form the b-ketoacyl intermediate bound to ACP. CO2 is a product and loss of CO2 pulls the reaction toward b-ketoacyl formation.

b-ketoacyl-ACP synthase

reduces b-keto group to the D-b-hydroxyacyl-ACP.

b-ketoacyl-ACP reductase

removes water and converts D-b-hydroxyacyl-ACP to trans-D2-acyl-ACP.

b-hydroxyacyl-ACP dehydratase

reduces the double bond to form a saturated acyl-ACP 2 carbons longer than the starting material.

Enoyl-ACP reductase

the two sites where a fatty acyl derivative can be found during fatty acid synthesis

4'-phosphopantetheine group on acyl carrier protein (ACP) and Cys on b-ketoacyl ACP synthase

in fatty acid synthesis, the reductive steps are the reverse of _______

beta oxidation

the overall process for the synthesis of palmitate from acetyl-CoA:

___ Acetyl-CoA + ___ATP + ___NADPH + ___ H+ ---->

Palmitate + ___ CoA + ___ ADP + ___Pi + ___NADP+ + ___ H2O

8; 7; 14; 14; 8; 7; 7; 14; 6

In making palmitate, we need ____ malonyl CoA and ____ acetyl CoA

7; 1

palmitate synthesis occurs in the ____. It takes more energy to make fatty acid than you get back out of it because some of the energy is lost as _____

cytoplasm; heat

In general, NADPH-->NADP+ is used for _____ _____, whereas NAD+-->NADH is used for ____ ______

NADPH is produced mainly by ____ _____ in adipocytes and by____ _____ _____ in hepatocytes.

synthetic reactions; energy generation; malic enzyme; pentose phosphate pathway

malate dehydrogenase reduces ______ to ____.

oxaloacetate; malate

malate is converted to _____ by ___ ____, producing _____

pyruvate; malic enzyme; NADPH

For each citrate coming out of the citrate shuttle, one ____ ___ and one ____ are produced

acetyl CoA; NADPH

the citrate shuttle moves citrate out of the ____ and into the ____. The net effect is to provide _____ in the _____ where fatty acid synthesis occurs

mitochondria; cytoplasm; acetyl CoA; cytoplasm

1 - malate dehydrogenase

2 - acetyl - CoA

3 - malate dehydrogenase

4 - NADP+

5 - NADPH + H+

6 - pyruvate malic enzyme

fill in the missing substrates and enzymes. What enzyme is responsible for 4--> 5?

The reaction catalyzed by _______ _______ is the rate-limiting step in the biosynthesis of fatty acids

acetyl-CoA carboxylase

When mitochondrial acetyl-CoA and ATP increase, citrate is transported ______ ____ ____. it then becomes both the precursor of _____ and an activation signal for _____ ______

out of mitochondria; acetyl-CoA; acetyl-CoA carboxylase

1 - citrate

2 - acetyl-CoA carboxylase

3 - Palmitoyl-CoA

fill in the diagram

in its _____ (dephosphorylated) form, acetyl-CoA carboxylase polymerizes into long filaments

active

In the well fed state the body wants to store energy so fatty acid synthesis should be turned _____ while lipase should be _____. So in the well fed state insulin is ____, glucagon is ____, cAMP is ____, so protein kinase A activity is _____, the hormone-sensitive lipase is in the _____ dephosphorylated state while the carboxylase is active because it is dephosphorylated.

on; off; up; down; down; down; inactive

Long-chain saturated fatty acids are synthesized from _______

palmitate

______ is the principal product of fatty acid synthesis

palmitate

palmitate can be lengthened to form ____ ____ (__:__) or longer saturated fatty acids. Palmitate moves to the _____ where elongation occurs by addition of ____ ____ units

stearic acid; 18:0; sER; 2 carbon

Desaturation of fatty acids requires what enzyme?

fatty acyl-CoA desaturase

two essential fatty acids

linoleic acid; linolenic acid

arachidonic acid can be synthesized from ___ ___

linoleic acid