Lipids II Flashcards

1
Q

Generation of Energy through Ketogenesis

Ketone bodies provide ____ energy than glucose because they enter the TCA ____. In liver, much of energy generated as Acetyl CoA is used to synthesize ____.

A

less
later
ketone bodies

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2
Q

Useful Definitions

 Ketogenesis-process by which ketone bodies are ____. ____ after meal

 ____-metabolic state where most of the body’s energy comes from ketone bodies in blood.

 Ketoacidosis-decrease in blood ____ due to ketone body dissociation-most often in ____ or ____ because ketone not adequately used as fuel

Amino acids that produce ____ or ____ are
Ketogenic:
they are Isoleucine ____, Phenylalanine, Tyrosine , ____, Leucine and ____

A

produced
12hours

ketosis

pH
diabetics
alcoholics

acetyl CoA
acetoacetate
threonine
tryptophan
lysine
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3
Q

Ketone Body Formation in Liver Mitochondria

Thiolase. The final step of the β- oxidation pathway runs ____

The liver is able to ____ ketone bodies but does not contain the enzymes to ____ them down for fuel- formation of ketone bodies is a mechanism by which the liver gets rid of ____ it does not need

A

backward

synthesize
break
fuel

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4
Q

ketone bodies formed in liver ____

liver = ____; provides energy to the body at its own expense; doesn’t have any of the enzymes in order to break it down

ketone body formation; similar to ____

formation of acetyl coA; intermediate in ____ metabolism

A

mitochondria
altruistic
b-oxidation
cholesterol

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5
Q

Regulation of Ketogenesis (REWATCH)

1. Increase in supply of ____ as high glucagon/insulin

  1. Malonyl CoA inhibition of CPT1 ____ (inactivation of ____)
  2. β-oxidation ____, ____ NADH and FADH2 enough ATP to supply energy needs of liver
  3. ____ converted to ____- enters cytosol for gluconeogenesis. ____ citrate synthase activity
  4. Acetyl CoA from ____ into ketogenesis
A
FA
lifted
acetyl CoA carboxylase
high
high
OAA
malate
low
TCA
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6
Q

Utilization of ketone bodies as fuel

 Ketone bodies are utilized by the ____ and to a much larger extent ____ and ____.
 Can be used by ____.
 Can cross placenta and be used by ____.
 CANNOT be used by ____ and ____

A
heart
brain
intestinal mucosa
fetus
liver
RBC
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7
Q

FA Synthesis

when we will synthesize FA > high ____, ____ > anabolic, synthesize

longer, more unsaturated, the more the ____

A

blood glucose
insulin
energy

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8
Q

Catabolic-process are ____, ____, ____ of energy

Anabolic- processes are ____, ____, ____ of energy

A

oxidative
LEO
production

reductive
GER
utilization

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9
Q

Fatty acid synthesis
Fatty acids used for fuel originate from
 ____ lipids
 Fatty acids released from ____ in adipocytes
 Synthesized in liver and delivered by ____

____ lipoprotein deliver FA for storage in adipocytes; dietary FA in ____

A

ingested
storage
lipoproteins

VLDL
chylomicrons

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10
Q

Role of Liver in Metabolism
• When blood glucose levels are ____ the liver synthesizes fatty acids which are delivered by ____ to other tissues. In times of excess caloric intake lipids can be synthesized from carbons obtained from ____ (mostly glucose and fructose) or ____.
• Fatty acids are the major ____ in the liver.

A
high
lipoproteins
carbohydrates
proteins
oxidative fuel
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11
Q

Fatty Acid Synthesis
Features
• Location: ____.
• Building blocks: ____ units (____)
derived mostly from carbohydrates, sometimes proteins.
• Reducing equivalent: ____ (electron donor)
• Energy Source: ____

• Fatty acids are highly reduced compounds therefore their synthesis requires enormous ____ input.
• The product, 16 C, palmitic acid, is the ____ for the synthesis of longer chain and monounsaturated fatty acids.
• Fatty acid synthesis is regulated ____ and through ____ modification and long term by ____
(FA beta oxidation is hardly regulated by ____)

A
cytosol
acetate
acetyl CoA
NADPH
ATP
energy
precursor
allosterically
covalent
gene expression
gene expression
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12
Q

Challenges of Synthesis
• The building blocks for synthesis are made in the ____, synthesis occurs in ____.
• Building blocks are ____ units and product is large ____ compound.
• Energy requiring process- where do we obtain reducing equivalents (NADPH)?
• Since it requires so much energy how do we regulate the process?
• How do we add double bonds? What does this cost the system?

A

mitochondrial matrix
cytosol
small water soluble
hydrophobic

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13
Q

High Fructose-corn syrup

• Conversion of Fructose to DHAP + G3P in red.
– These two compounds are intermediates of ____ and are converted in the liver principally to glucose, glycogen, or fatty acids.
• In the liver, ____ cleaves both Fructose 1-phosphate in the pathway for ____ and Fructose 1,6- bisphosphate in the pathway for ____.

• FRUCTOSE METABOLISM BYPASSES ____- major regulatory point of glycolysis- therefore the generation of ____ and ____ not regulated if carbon source is fructose. The fructose serves as an ____ source of intermediates for hepatic lipogenesis

A

glycolysis
aldolase B
fructose metabolism
glycolysis

PFK
G3P
pyruvate
unregulated

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14
Q

High Fructose-corn syrup

glucose has a ____ form; fructose has no ____ (everything ingested will form intermediates for ____)

bc fructose bypasses phosphofructose step > fructose metabolism is completely ____ > generates ____ and ____ (which is then precursor for ____ in the mitochondria)

fructose is more ____ than glucose

A

storage
storage
FA

unregulated
G3P
pyruvate
acetyl CoA

detrimental

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15
Q

Reciprocal regulation of PC and PDH

Pathway followed by mitochondrial pyruvate is dictated by mitochondrial ____ concentrations

Increased mitochondrial Acetyl CoA will
• Feedback inhibit-____
• Activate-____

As OAA condenses with Acetyl CoA to form citrate
• PDH activity ____
• PC activity ____

  1. Pyruvate carboxylase (forms OAA from pyruvate)
  2. Pyruvate dehydrogenase (forms acety CoA from pyruvate)
A

acetyl CoA

pyruvate dehydrogenase
pyruvate carboxylate

increase
decrease

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16
Q

Since Acetyl Co A cannot cross the ____ how do we obtain sufficient amounts of acetate units (2 Carbon building blocks)?

Convert the Acetyl Co A into an intermediate that can cross the membrane- ____

  1. Pyruvate carboxylase
  2. Pyruvate dehydrogenase- activated by ____
A

mitochondrial matrix
citrate
insulin

17
Q

citrate cross mito membrane to exit > once outside in cytoplasm, converted to ____ and ____

OAA converted to ____ (cytosolic) > goes to ____ (via malic enzyme)

A

OAA
acetyl CoA

malate
pyruvate

18
Q

Formation of Malonyl CoA

____ in fatty acid synthesis
Acetyl Co A is ____.
The reaction is catalyzed by ____ and requires energy in the form of ____.
____ ready to be used in the synthesis of fatty acids.

reaction is a ____ carboxylation; biotin attached via a ____ residue

biotin residue is used to transfer the _____ to the acetyl CoA

A
committed step
carboxylated
acetyl CoA carboxylase
ATP
malonyl CoA

biotin-dependent
lysine
CO2

19
Q

Biotin Dependent Carboxylases

Biotin is an _____. Biotin-dependent carboxylases are enzymes that add _____ to substrates, making use of a _____ biotin prosthetic group.
Adequate intake (AI) set by Institute of Medicine. _____/day
Sources: eggs, _____, _____, milk

Biotin deficiencies
• _____ ( hair loss)
• Dry scaly red _____
• _____

A
essential nutrient
CO2
covalently-linked
30ug
almonds
legumes

alopecia
rashes
lethargy

20
Q

Strategy of FA synthesis

add _____ carbon units at a time; through a series of reactions, go from a more _____ to a more _____ structure

each reaction you lose a carbon (each condensation)

requires _____ NADPH for palmitate (16C)

A

2
oxidized
reduced

21
Q
Steps of fatty acid synthesis
• \_\_\_\_\_- loss of CO2
• \_\_\_\_\_- catalyzed by reductase
• \_\_\_\_\_-catalyzed by dehydratase
• \_\_\_\_\_- catalyzed by reductase

Catalyzed by a _____ polypeptide with _____ different catalytic sites.

A

condensation
reduction
dehydration
reduction

single
7

22
Q

Fatty Acid Synthase Complex (REWATCH)

The reactions of the synthesis are catalyzed by a unique multi-enzyme complex called _____. FAS is made up of numerous enzymes in _____ different domains arranged as a _____.

This design of the synthase aids in:
Enhancing _____
Preventing the _____
Protecting substrates from _____.

A

fatty acid synthase (FAS)
three
dimer

reaction efficiency
dilution of reactants
competing reactions

23
Q

Organization of the FAS complex

• The two dimers of the FAS complex are aligned _____. This allows for the transfer of the growing fatty acyl chain from the _____ on ACP to the _____ of another subunit.

ACP = acyl carrier protein
CE = condesning enzyme

panthatonic acid rings in _____; attached to ACP through a _____

A

anti-parallel
PantSH
Cys-SH

ACP
cysteine

24
Q

Organization of the FAS complex

thioesterase is used at the end of synthesis in order to _____ the 16C FA from the polypeptide

role of ACP = carries acyl groups in _____ linkage
role of condensing enzyme = _____ acyl and malonyl groups

A

cleave
thioester
condenses

25
Q

ACP interacts with _____ on the opposite monomer; one FA is synthesized in each side of the red line (so _____ FA are formed per one FAS [which is a _____])

A

CE
2
dimer

26
Q

ACP holds _____; CE holds the _____

first step condensation: lose _____; ACP is now holding an acyl chain with _____ (2 of the 4 are attached to an _____)

first step reduction > putting _____ intot the system; then a _____

ACP switches out the growing acyl chain to the _____ so the new _____ can come in

Growing hydrocarbon chain is elongated _____C’s at a time

Malonyl always linked to _____

A

malonyl
acetyl

CO2
4 carbons
oxygen

NADP
dehydration

CE
malonyl

2

ACP

27
Q

grow palmitate; then cleaved by _____; works becasue the distance between TE is actually the _____ of the hydrocarbon

A

TE

length

28
Q

Overall Reaction
• 8 Acetyl Co A + 14NADPH + 7ATP
16C Palmitic acid + 14NADP+ + 7 CoASH+ 7CO2+ 7ADP+7Pi

Thus synthesis- prior the addition of any double bonds requires:
_____ NADPH _____ ATP

A

14

7

29
Q

Energy Sources
Note:
In order to form Acetyl CoA and regenerate malate we use 1 ATP during _____ step and 1 NADH during _____ step. Thus in addition to the energy required for fatty acid synthesis directly, additional energy is required to _____ building blocks.

_____ NADPH as convert malate to pyruvate (regenerate); you get the remainder from the pentosphosphate pathway

A

citrate lyase
malate dehydrogenase
transport

8

30
Q

Fatty Acid Elongation

Elongation: beyond the 16-C length of the palmitate product of FAS occurs two carbons at a time in _____.

The series of reactions is reduction, dehydration, reduction. Utilizing 2 _____ per 2 _____ atoms added.

A

endoplasmic reticulum
NADPH
carbon

31
Q

Fatty Acid Desaturation
• Introduction of double bonds, requires a _____ enzyme that utilizes _____ and _____ for each double bond added.
• Desaturase specific for _____ of double bond
• Occurs in _____.
• More complex the FA more energy is _____ to synthesize it

cannot introduce double bond past 10; so you’re adding to the side that is attached to the _____ (<10)

A
desaturase
O2
NADH
position
endoplasmic reticulum
required
CoA
32
Q

Regulation of Acetyl CoA Carboxylase
• Allosteric-_____
•Dephosphorylation/Phos. by Insulin, AMP- _____

_____ energy indicator activated when AMP/ATP _____

A

citrate
kinase
low
high

33
Q

acetyl CoA carboxylase is _____ when phosphorylated; high glucose meal, increase insulin > activates a _____

SYSTEMIC REGULATION

cytosolic citrate (alloesterically feed forward) activates _____, in the presence they form long monomers

_____ feedback inhibit the enzyme

A

inhibited
phosphatase

acetyl CoA carboxylase
palmitoyl CoA

34
Q

Reciprocal Regulation
• To avoid a _____
• The product of Acetyl CoA carboxylase – Malonyl CoA inhibits _____ thus fatty acids do not enter _____ for oxidation.
• Acyl CoA inhibits the _____ – allowing fatty acids to _____ mitochondria for oxidation

A
futile cycle
carnitine palmitoyl transferase
mitochondira
acetyl CoA carboxylase
enter
35
Q

What is fate of newly synthesized FA?
• Incorporated into _____
• Liver-Delivered to other tissues packaged in _____
• Adipocytes-_____- until needed for fuel

A

phospholipids
VLDL
stored

36
Q

TAG and Phospholipid (PL) synthesis

_____ is diverted for phospholipid synthesis (precursor for PL synthesis)

if it is not diverted it is the precursore for formation of _____

NOTE: adipocytes do not contain _____

A

phosphatic acid
TAG
glycerol kinase

37
Q

Very Low Density Lipoproteins deliver TAG synthesized by the _____

_____ in the liver (apoB48 in the intestine)

synthesis occurs in _____

A

liver
apoB100
RER

38
Q

Very Low Density Lipoprotein Formation and Function

  1. Protein synthesis _____
  2. Packed with TAG –_____
  3. Secreted in secretory _____

 _____ hydrolyzes the TAGs in the VLDL to provide fatty acids for the surrounding tissues.
 _____ on VLDL also activate LPL

A

RER
golgi
vesicles

lipoprotein lipase (LPL)
Apo-CII
39
Q

Regulation of gene expression by diet
• Long-term fat free-high carbohydrate diet
– _____ mediated regulation of _____. Insulin induces _____, malic enzyme, _____ and FAS expression.

– High fat diets (Atkins) result in a _____ in the levels of Acetyl CoA Carboxylase and FAS.

A
insulin
gene expression
citrate lyase
acetyl CoA
carboxylase
decrease