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28 Cards in this Set

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What is the purpose of fatty acid synthesis? Where does it occur? What goes in/out? Regulation?
Energy Storage
Location: Cytoplasm of hepatocytes
Acetyl CoA-->Fatty Acids
Regulation: Rapid control via AcCoa carboxylase
In what type of environment are fatty acids stored? What does this allow for?
Non-aqueous environment; allows for large stores
How do energy sources change from the fed state to post-absorptive state? 24 fast? 72 hour fast?
Fed: Energy from diet
Post-Absorptive: Glycogen breakdown
24 hour fast: Gluconeogenesis
72 hour fast: FA oxidation (not as glucose!)
What are examples of esterified fatty acids? How are unesterified fatty acids transported in blood?
Esterified: TG's, cholesterol ethers, phospholipids

Must circulate while bound to ALBUMIN
What are the essential fatty acids?
Linoleic Acid and Linolenic Acid
Describe the first step of fatty acid synthesis.
Acetyl Group Shuttle:
Acetyl CoA from inside mitochondria to cytosol via Citrate
Describe the second step of FA synthesis.
Malonyl CoA Synthesis:
RATE LIMITING STEP!
Acetyl-CoA Carboxylase is RATE LIMITING ENZYME for FA Synthesis
Regulated by insulin and counterregulatory hormones
What's the rate limiting enzyme for FA synthesis? How is it regulated?
Acetyl CoA Carboxylase
Insulin, Norepi, Glucagon
Describe the third reaction of fatty acid synthesis. What's the energy source that drives this reaction?
Malonyl-CoA + Acetyl CoA + NADPH-->Palmitate
Via Fatty Acid Synthetase Complex (REDUCTION REACTION!!!)

Driven by NADPH (14 of them) from HEXOSE MONOPHOSPHATE PATHWAY
What is the fatty acid synthase complex? What is its overall reaction? Requirements?
Complex of 7 enzymes that facilitate successive steps in FA synthesis

General: Lengthens FA by 2C's via REDUCTION REACTION!!!

Requires acyl carrier protein (ACP) and Pantothenic acid (vitamin)--latter is what malonyl-coA binds
What steps occur after formation of Palmitate? Where do these steps occur?
Elongation: ER and mitochondria in brain and adrenal gland

Desaturation: ER and catalyzed by oxidases
If vertebrates lack the enzyme to convert oleic acid to linoleic acid, how is this acid obtained?
Through diet. It's an essential fatty acid. As is linolenic acid.
Describe the three fatty acids esterified to glycerol.
They're usually different, C1 saturated, C2 unsaturated, C3 can be either

It's complicated.
What two functions do white fat cells serve?
Energy Storage

Metabolic functions: make cytokines (for inflammation)
What is the purpose of fatty acid degradation? Where does it occur? What goes in/out? Regulation?
Purpose: Provision of energy
Location: mitochondria (it's oxidation)
Dietary and Stored FA's-->CO2 + H2O + ENERGY (once completely oxidized) OR KETONE BODIES (in liver)

Regulation: transport into mitochondria via carnitine shuttle
Describe the first step in fatty acid oxidation.
Triacylglycerol (stored in fat cells)-->
Diacylglycerol + FFA-->
Monoglyceride + FFA-->
Glycerol + FFA

All via Hormone-Sensitive Lipase: activated by cAMP-dependent kinase; inactivated by insulin
Describe the second step in fatty acid oxidation.
Mitochondrial Transport in Liver Cell:
Outer mitochondrial membrane:
RCOO- + CoA-SH+ATP-->RCO-S-CoA
via Faty Acyl-CoA Synthase

RCO-S-CoA + Carnitine-->
RCO-Carnitine + CoA-SH
Via CPT1

RCO-Carnitine + CoA-SH-->
RCO-S-CoA in inner mitochondrial membrane
via CPT II

THIS IS THE REGULATORY POINT IN FATTY ACID OXIDATION!!!!
Why are only long-chain fats subject to regulation?
Carnitine transport system is required for importing FA's of chain length longer than 12C's.
What is the third step of FA oxidation?
RCO-S-CoA + FAD-->Enoyl-S-CoA + FADH2

Via Acyl-CoA Dehydrogenase
Via what reaction is most energy derived from fat?
beta-oxidation
What do steps 4 to 7 of FA oxidation result in? Quantify this in terms of ATP.
Enoyl-S-CoA-->-->-->8 acetyl-S-CoA + 7FADH2 + 7NADH + 7H+

2ATP per FADH2
3 ATP per NADH
=35 ATP
8 acetyl=CoA-->96 ATP
Total: 131 ATP per mole
Describe the steps of ketogenesis. When and where do these reacitons occur?
How is ketogenesis triggered?
In fasted state, have net flux of OAA-->Glucose (gluconeogenesis)

Decrease in OAA --> decreased acetylCoA used for citrate formation

acetyl CoA then preferentially convereted to acetoacetate (AcAcCoA)

So ketogenesis behaves as an overflow PW for AcCoa
What's the effect of carbohydrate availability on ketogenesis?
Low cab availability-->increased hepatic ketogenesis
Explain diabetic ketoacidosis.
Lack of insulin stimulates lipolysis in periphery
Released TG's transported to liver where ketogenesis is fully activated

Results in diabetic ketoacidosis
What's the purpose of alpha-oxidation? Location? In/out? Regulation? Clinical relevance?
Purpose: metabolize Fa's that can't undergo direct beta-oxidation
Location: Peroxisomes
FA (alpha-carbon is substrate for hydroxylation)-->alpha-OH FA's

Regulation: Substrate-driven
Clinical Note: Defective in REFSUM'S DISEASE
What's the purpose of omega-oxidation? Location? In/out? Regulation? Clinical notes?
Purpose: Alternative metabolism of FA's
Location: Extra-mitochondrial (microsomal)
In/Out: FA (omega-carbon)-->Dicarboxylic FA's
REgulation: Substrate-driven
Notes: Upregulated if beta-oxidation defective
What are symptoms of MCAD?
Medium Chain Acyl-CoA DH Deficiency:
Fatty Liver
No ketonuria
Hypoglycemic
Accumulation of medium chain fatty acids (octanedioic, nonanedioic, decanedioic acids)