lecture 27: synthesis of Triacyl glycerols and major membrane lipids

what is phosphatidic acid?

A phosphorylated glycerol with 2 FA tails, intermediate to triglyceride production

what are the two sources of phosphatidic acid?

-glycerol from the liver
-glucose from adipose tissue and liiver

synthesis of phosphatidic acid from glycerol

-liver uses glycerol kinase

adipose tissue can only produce TGs IF

glycolysis is a ctiive

dephosphorylation of phosphatidic acid produces

DAG
-addition of another acetyl CoA produces triacylglycerol to be released to blood VLDL or adipose stores

Liver exports TAG as ________

VLDL

components of VLDL

-lots of TG
-mores phospholipids and cholesterol esters present

VLDL synthesis in the liver

-glycerol-3-phosphate + FACoA make TG
-PPP and TCA cycle must be active to generate precursors
-TGs are packaged into VLDL with the help of MTP and apoB-100 into the blood

describe the process of VLDL assembly

-proteins are made in the rough ER
-lipids are added in smooth ER and golgi
-secretory vesicles take particles to plasma membrane for release

role of lipoprotein lipase

-cleaves TG into FA and glycerol
-contributes to transformation of VLDL to IDL to LDL

what activates lipoprotein lipase?

ApoCII on VLDL or chylomicron

Muscle lipoprotein lipase

-low Km (high affinity)
-helps put TGs into work!

Adipose lipoprotein lipase

-high Km (low affinity)
-helps prevent overstorage

how are triglycerides degraded?

-glucagon activates protein kinase A
-PKA phosphorylates and activates HSL and ATGL
-ATGL cleaves first fatty acid, HSL the second
-other lipases complete the process and fatty acids and glycerol are released into circulation

ATGL (adipose triglyceride lipase)

what breaks a triglyceride into a diglyceride?
-rate limiting enzyme for triglyceride degradation

HSL (hormone sensitive lipase)

what breaks a Diglyceride into a Monoglyceride?
-activated by PKA

what regulates HSL?

-glucagon activates PKA
-PKA phosphhorylates and ACTIVATES HSL

relationship of insulin and LPL

-insulin stimulates synthesis and release of LPL
-leads to TG synthesis and storage

relationship of glucagon and HSL

-glucagon activates enzymes that break down TGs and cause release of fatty acids for metabolic use

if LPL and HSL were both active...

there would be a futile cycle of TG synthesis and degradation

structure of glycerophospholipids

1. Contains glycerol as a backbone
- Esterified to two fatty acids
- Third posistion of a phosphate which in turn in linked to a nitrogen containing base (polar/hydrophilic head group)

Ex: PIP2, phosphatidyl glycerol, cardiolipin

glycerophospholipid synthesis

-phosphorylated head group is degraded by CTP to form a diacyl glyceride, ultimately forming a glycerophospholipid

-different orders can be used, YOU ALWAYS USE CTP

can head groups of glycerophospholipids be interconverted?

yes!
ex: phasphatidylethanolamine
-externalizing the phosphatidylserine is associated with programmed cell death

benefit of lung surfactant

-lung surfactant reduces the surface tension of water lining the alveolar sac, preventing collapse
-low surfactant causes distress in premature infannts

which glycerophospholipid is surfactant?

dipalmitoylphosphatidylcholine is a major component
-phosphatidylcholine which develops at 35 weeks utero
-cholesterol
-apolipoproteinis: Sp-A, Sp-B, Sp-C

Types of Sphingolipids

sphingophospholipids and glycolipids

structure of sphingomyelin

-sphingosine back bone
-fatty acid
-phosphate with a head group

-ex of sphingophospholipid

structure of glycolipids

-sphingosine backbone
-fatty acid
-carbohydrate
-ex: cerebrosides, sulfadidies

relevance of sphingolipids

-important in nervous system
-used in intercellular signaling, ABO blood groups
-binding sites for viruses and toxins
-based on ceramide backbone

how is the ceramide formed for sphingolipids?

-serine and palmitoyl coA condense

what is attached to the ceramide inn sphingomyelin

choline

Phospholipase A1 and A2

-remove fatty acids at 1 and 2 for glycerophospholipid degradation

phospholipase A2 activity leads to release of

arachidonic acid

phospholipase C

removes phosphorylated head group for glycerophospholipid degradation

phospholipase C activity can triigger

release of DAG and IP3 from PIP2

phospholipase D

removes head group in for glycerophospholipid degradation

phospholipase D activity produces

phosphatidic acid

sphingolipids are degraded by

lysosomal enzymes