Lipids II Flashcards
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 ____.
less
later
ketone bodies
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 ____

produced
12hours
ketosis
pH
diabetics
alcoholics
acetyl CoA acetoacetate threonine tryptophan lysine
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
backward
synthesize
break
fuel
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
mitochondria
altruistic
b-oxidation
cholesterol
Regulation of Ketogenesis (REWATCH)
1. Increase in supply of ____ as high glucagon/insulin
- Malonyl CoA inhibition of CPT1 ____ (inactivation of ____)
- β-oxidation ____, ____ NADH and FADH2 enough ATP to supply energy needs of liver
- ____ converted to ____- enters cytosol for gluconeogenesis. ____ citrate synthase activity
- Acetyl CoA from ____ into ketogenesis
FA lifted acetyl CoA carboxylase high high OAA malate low TCA
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 ____
heart brain intestinal mucosa fetus liver RBC
FA Synthesis
when we will synthesize FA > high ____, ____ > anabolic, synthesize
longer, more unsaturated, the more the ____
blood glucose
insulin
energy
Catabolic-process are ____, ____, ____ of energy
Anabolic- processes are ____, ____, ____ of energy
oxidative
LEO
production
reductive
GER
utilization
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 ____
ingested
storage
lipoproteins
VLDL
chylomicrons
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.
high lipoproteins carbohydrates proteins oxidative fuel
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 ____)
cytosol acetate acetyl CoA NADPH ATP
energy precursor allosterically covalent gene expression gene expression
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?
mitochondrial matrix
cytosol
small water soluble
hydrophobic
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
glycolysis
aldolase B
fructose metabolism
glycolysis
PFK
G3P
pyruvate
unregulated
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
storage
storage
FA
unregulated
G3P
pyruvate
acetyl CoA
detrimental
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 ____
- Pyruvate carboxylase (forms OAA from pyruvate)
- Pyruvate dehydrogenase (forms acety CoA from pyruvate)
acetyl CoA
pyruvate dehydrogenase
pyruvate carboxylate
increase
decrease
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- ____
- Pyruvate carboxylase
- Pyruvate dehydrogenase- activated by ____
mitochondrial matrix
citrate
insulin
citrate cross mito membrane to exit > once outside in cytoplasm, converted to ____ and ____
OAA converted to ____ (cytosolic) > goes to ____ (via malic enzyme)
OAA
acetyl CoA
malate
pyruvate
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
committed step carboxylated acetyl CoA carboxylase ATP malonyl CoA
biotin-dependent
lysine
CO2
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 _____
• _____
essential nutrient CO2 covalently-linked 30ug almonds legumes
alopecia
rashes
lethargy
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)
2
oxidized
reduced
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.
condensation
reduction
dehydration
reduction
single
7
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 _____.
fatty acid synthase (FAS)
three
dimer
reaction efficiency
dilution of reactants
competing reactions
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 _____
anti-parallel
PantSH
Cys-SH
ACP
cysteine
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
cleave
thioester
condenses
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 _____])
CE
2
dimer
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 _____
malonyl
acetyl
CO2
4 carbons
oxygen
NADP
dehydration
CE
malonyl
2
ACP
grow palmitate; then cleaved by _____; works becasue the distance between TE is actually the _____ of the hydrocarbon
TE
length
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
14
7
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
citrate lyase
malate dehydrogenase
transport
8
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.
endoplasmic reticulum
NADPH
carbon
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)
desaturase O2 NADH position endoplasmic reticulum required CoA
Regulation of Acetyl CoA Carboxylase
• Allosteric-_____
•Dephosphorylation/Phos. by Insulin, AMP- _____
_____ energy indicator activated when AMP/ATP _____
citrate
kinase
low
high
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
inhibited
phosphatase
acetyl CoA carboxylase
palmitoyl CoA
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
futile cycle carnitine palmitoyl transferase mitochondira acetyl CoA carboxylase enter
What is fate of newly synthesized FA?
• Incorporated into _____
• Liver-Delivered to other tissues packaged in _____
• Adipocytes-_____- until needed for fuel
phospholipids
VLDL
stored
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 _____
phosphatic acid
TAG
glycerol kinase
Very Low Density Lipoproteins deliver TAG synthesized by the _____
_____ in the liver (apoB48 in the intestine)
synthesis occurs in _____
liver
apoB100
RER
Very Low Density Lipoprotein Formation and Function
- Protein synthesis _____
- Packed with TAG –_____
- Secreted in secretory _____
 _____ hydrolyzes the TAGs in the VLDL to provide fatty acids for the surrounding tissues.
_____ on VLDL also activate LPL
RER
golgi
vesicles
lipoprotein lipase (LPL) Apo-CII
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.
insulin gene expression citrate lyase acetyl CoA carboxylase decrease
