Lipid Metabolism Flashcards by Emily Cross

what is the major source of carbon for fatty acid synthesis?

dietary carbons

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fatty acid synthesis overview

occurs in liver
secondarily in adipose, brain, kidneys, lactating mammary glands

requires coordination btwn cytosolic and mitochondrial rxns

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precursor and end product of FA synthesis

acetyl coA 2C

palmitic acid 16C

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list the 3 phases of fatty acid synthesis

cytosolic entry of acetyl coA
- –made in mito matrix but needed in cytoplasm
generation of malonyl coA
- –acetyl coa is carboxylated to malonyl coA
- –most important substrate in FA synthesis
- –***rate limiting rxn
fatty acid chain formation
- –FA synthase catalyzes 7 rxns to incorporate acetyl coa and malonyl coa into palmitate

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list the first 4 steps in FA synthesis

condensation of acetyl coa w/ oxaloacetate = citrate
- –citrate synthase
transport of citrate from mito to cytosol
- –via citrate lyase
citrate converted back to acetyl coa and OAA
- –citrate lyase
- –acetyl coa can now be used for FA synthesis in cytosol
OAA reduced to malate
- –malate dehydrogenase

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steps 5 and 6 of FA synthesis

malate transported into mito via malate a-ketoglutarate transporter
- –oxidized to OAA
- –malate dehydrogenase
cytosolic malate converted to pyruvate
—malic enzyme
pyruvate transported to mito via pyruvate transporter
—carboxylated to OAA by pyruvate carboxylase

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presence of citrate and insulin will ______ FA synthesis while glucagon, epinh, high [AMP], palmitate, PUFA will ______ synthesis

increase

decrease

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conversion of acetyl CoA to malonyl CoA by carboxylation

catalyzed by acetyl coa carboxylase ACC

**rate limiting enzyme of fatty acid synthesis

ACC adds CO2 to acetyl coa

-uses ATP
–uses biotin as cofactor

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malonyl CoA

regulator — inhibits carnitine acyltransferase
**rate limiting step in FA degradation

prevents FA synthesis and degradation from occurring simultaneously

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regulators of phase 3 in FA synthesis

promoters:
insulin
glucocorticoid hrs

inhibitory
PUFA

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describe FA chain formation

2 C from malonyl coa are sequentially added to growing FA chain

–occurs in 7 rxns
–forming palmitate (16:0)

these rxns occur on FA synthase complex (FAS complex)

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FAS

multi-enzyme complex

composed of 2 dimers arranged head to tail

each has 7 enzyme activities
an acyl carrier protein ACP

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palmitate synthesis

1 acetyl coa + 7 malonyl coa + 14 NADPH + 14 H+

CH3(CH2)14COO- + 14 NADP+ + 8 CoA + 6H20

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what is the purpose of reduction rxns in the FAS reactions?

using dehydration of NADPH to remove double bonds

creating a fully saturated growing FA

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what are the sources of NADPH?

malic enzyme = 1

PPP = 2-12

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list the 7 rxns in FA synthesis for creating palmitate

acetyl ACP
malonyl ACP
- –condensation
acetoacetyl ACP
- –reduction
D-3 hydroxbutyryl ACP
- –dehydration
crotonyl ACP
- –reduction
butyryl ACP
palmitate

occurs 7x total = C16

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list the main rxns of the 3 phases in FA synthesis

ATP citrate lyase
citrate —> acetyl coa + OAA
acetyl coa carboxylase
**rate limiting step
acetyl coa + CO2 —> malonyl coa
FA synthase
4C FA - repetition —> 16C palmitate

regulation of ATP citrate lyase

stimed by phosphorylation

gene expression induced by glucose/insulin

gene expression inhibited by:
PUFA
leptin

PUFA

polyunsaturated FAs

regulation of acetyl CoA carboxylase

inactive dimer – active polymer

allosteric regulation
phosphorylation/De-phos
induction

allosteric regulation of acetyl coa carboxylase

citrate +

long chain FA/palmitate -

phosphorylation control of acetyl coa carboxylase

phos = +
insulin

de-phos = -
epinh
glucagon
AMP

control of gene expression induction - acetyl coa carboxylase

gene exp up regulated by high carb/low fat diet

regulation of FAS

allosteric reg — presence of phosphorylated sugars increases activity

gene expression control:
+ = insulin, glucocorticoid hrs, high carb/low fat diet
- = high fat diet, starvation, PUFA

synthesis of longer chain FA

elongation of palmitate occurs in SER or mito occurs 2C at a time NADPH has reducing power brain cells need longer FA chains C18-24

carbon donors for longer chain FA synthesis

SER uses malonyl coa mito uses acetyl coa

desaturation of FAs

inducing double bonds occurs in SER catalyzed by acyl coa desaturases humans can add DB btwn carbons: 4-5, 5-6, 6-7, 9-10 but humans cannot make 9-10 DBs must ingest thru diet as omega 3/6 FAs

essential fatty acids

humans cannot make w-3 or w-6 FAs must ingest their precursors as: linoleic acid linolenic acid

nomenclature of FAs

based on position of carbon from methyl end = omega end 6C away from methyl = w-6

what is the importance of not being able to create DBs between the 9-10 carbons?

these fatty acids are very important for development and functioning ex. EPA and DHA

eicosanoid hormones

arachidonate FA derived from linoleate major precursor for signal molecules prostaglandin yields 9 major classes of prostaglandins called PGA to PGI

describe eicosanoid hormones

local short lived hormones ``` influencing activities of cells inflammation blood flow ion transport synaptic transmission induce sleep ```

clinical example of eicosanoid hormone

aspirin blocks enzyme that converts arachidonate into prostaglandin blocking this step interferes w/ signaling pathways such as: inflam, fever, pain, blood clotting

major storage form of FAs

triacylglycerol or TAG have almost 7x more nrg than carbs a glycerol head 3 FA chains attached

sources of TAGs

diet processed in intestines hepatocytes and adipocytes

perilipin

family of proteins that coat lipid droplets in adipose and muscle cells regulate lipolysis by controlling physical access to TAGs are regulated by PKA overexpression of perilipin1 inhibits lipolysis KO peilipin increases it **used for obesity treatment

first phase of FA activation

occurs in cytosol need to get FA into mito but the memb is not permeable to FAs acyl-coa synthetase traps FA in cells ---making it metabolically active

translocation to mito matrix

carnitine converted to acyl carnitine - --which can be moved into mito - --via carnitine acyltransferase II acyl carnitine can be converted back to carnitine in mito ---via carnitine acyltransferase II

4 steps of B-oxidation

1. oxidation acyl coa dehydrogenase 2. hydration enoyl coa hydratase 3. oxidation 3-hydroxyacyl coa dehydrogenase 4. thiolysis acetyl coa acetyltransferase **these steps are repeated until FA broken down into acetyl coa

the 4 main steps of B-oxidation generate?

FADH2 (14) ---delivers e- to ETC NADH (21) ---delivers e- to ETC ``` acetyl coa (96) ---enters TCA cycle ``` 14+21+96 = 131 2 ATP used = 129 net ATP

ketone bodies

water soluble, acidic compounds 1. acetoacetate 2. B-hydroxybutyrate 3. acetone produced in liver only provide nrg for tissues and brain during fasting/starvation

utilization of acetoacetate

acetoacetate to acetoacetyl coa ---coa transferase to 2 acetyl coa ---thiolase