Lipid Metabolism Flashcards
Function of Lipids
Fuel stores (provide energy), structural components (plasma membranes), signaling molecules (signal transduction pathways), other (insulation, generating heat, fat digestion)
Fatty acid synthesis
- occurs primarily in the liver
- requires coordination between cytosolic and mitochondrial reactions
- the precursor is Acetyl CoA
- Three phases
- methyl and carboxyl ends
Phase 1 Fatty acid synthesis
cytosolic entry of acetyl CoA (from mitochondria)
- oxaloacetyate + acetyl CoA –> Citrate (via citrate synthase)
- citrate transported from mitochondria to cytosol, then citrate lyase –> OAA + Acetyl coA
- oxaloacetyate + acetyl CoA –> Citrate (via citrate synthase)
Rate limiting enzyme fatty acid synthesis
Acetyl CoA carboxylase carboxylates acetyl CoA --> Malonyl CoA - upreg by insulin, citrate - downreg by glucagon, epinephrine, high AMP, palmitate, PUFA - This is phase 2 FA synthesis
Phase 3 fatty acid synthesis
FA synthase catalyzes 7 reactions malonyl CoA + Acetyl CoA ——> palmitate
- FA synthase = 7 enzymes and carrier protein
- Condensation, reduction, deydration, reduction for each of the 7 reactions
- upreg by phos sugars, glucocorticoid hormones, high carb/low fat diet, insulin
- down reg by high fat diet (starvation), PUFAS
Synthesis of TAG in intestinal cells
- promoted by dietary TAG - broken down into MAG + Free FA in intestinal lume, separately transported into intestinal cell
2. Fatty acyl coA synthase turns FA into Fatty acyl CoA (ATP –> AMP)
3. MAG + Fatty acyl CoA –> Diacyl Glycerol (DAG)
4. DAG acyl transferase + DAG –> TAG in intestinal cell, with side products apolipoproteins and other lipids.
5. TAGs packaged into chylomicrons and put into bloodstream
Synthesis of TAGs in Liver
- Promoted by excess carbs
1. glucose + glycerol –> Glycerol-3-Phos (G-3-P)
2. G-3-P backbone for TAG synthesis
FFA (synthesized in liver from acetyl coA) added to G-3-P to form TAGS
3. TAGs packed w/ apolipoproteins and other lipids –> VLDL, released to bloodstream as VLDL
Synthesis of TAGs in Adipocytes
- promoted by excess carbohydrates and fats
1. glucose + glycerol –> Glycerol-3-Phos (G-3-P)
2. G-3-P backbone for TAG synthesis
3. FFA obtained from breakdown of chylomicrons and VLDL in blood, by action of capillary lipoprotein lipase
4. G-3-P and FFA form TAGS, then stored in adipocytes
Synthesis of longer chain fatty acids
Elongation - palmitate converted to longer chain FA in smooth ER or mitochondria
- uses NADPH as reducing power
in SER - Malonyl CoA as C donor
in mitochon. - uses Acetyl CoA as donor
Desaturation/unsaturation
Occurs in smooth ER, uses NADPH and O2, catalyzed by Acetyl coA denaturases (4 different types in humans - 4, 5, 6, 9)
Linoleic acid
omega 6 fatty acid
- used to make arachidonic acid (precursor for eicosanoids)
Linolenic acid
omega 3 fatty acid
- used to make icosapentanoic acid (EPA) and DHA (docosahexanoic acid)
TAG breakdown
4 major lipases used: ATGL, HSL, LPL, MAG lipase
- stimulated by hunger and exercise
- glucagon and epinephrine bind to GPCR (Gs), activates adenylate cyclase –> activates cAMP –> PKA
- PKA phosphorylates HSL
- PKA also phos perilipin –> phos ATGL,
TAG –> DAG –> MAG –(MAG lipiase)–> FA + glycerol
Perilipin
proteins that coat lipid droplets in adipocytes and muscle cells
- regulate lipolysis by controlling physical access to HSL (block them from doing their job to TAG)
(phosphorylation of perilipin allows for association between HSL and TAG)
- overexpression inhibits lypolysis, knockout causes easy lipolysis
Catabolization of Fatty acids (phase 1)
Occurs in cytosol (process of transfering FA to mit.matrix. Need to be activated
- Fatty acid crosses into cytosol from adipocyte
- fatty acyl coA synthetase (+ATP) makes Fatty acyl coA so it can cross through outer mitochond. membrane
- Carnitine palmitoyltransferase-1 (rate limiting step) transfers Fatty Acyl from FA-CoA to carinitine –> forms FA carnitine.
- carnitine acylcarnitine translocase - antiporter (FA-Carnitine in and carnitine out) in intermembrane space
- carnitine palmitoyl transferase II - located in inner mitochondrial membrane, transfers fatty acyl from FA-carnitine to CoA, forms FA-CoA