Lipids Flashcards
SREBP-2 (2)
Derived from a separate gene
It is 45% identical to SREBP-1a
How may dietary fatty acids alter gene expression of the LDL receptor (2)
May alter balance between free and esterified cholesterol
In the liver
Which lipogenic genes may PUFA down regulate (4)
SREBP-1c
ACC
FAS
SCD
Which FA oxidation genes may PUFA up regulate (3)
CPT-1
Acyl CoA oxidase
L-FABP
How do n3 PUFA influence SREBP-1c mRNA concentrations (2)
Reduction in the transcription of the SREBP-1c gene
Decreased stability of SREBP-1c mRNA
What protein regulates expression of LDL receptor and HMGCoA reductase genes (3)
Promoter of cholesterol regulated genes contains a sequence known as SRE
The cells of SRE contains SREBP
Which exits in an immature form in the endoplasmic reticulum
How SREBP regulates LDL receptor gene expression (5)
SREBP is escorted to Golgi Apparatus by SCAP
SREBP is then attacked by S1P and S2P
This leads to the release of a mature SREBP into cytosol
Mature SREBP then translocates into nucleus
And binds to SRE on the promoter of target genes
What happens to SREBP in the presence of cholesterol (high SFA diet) (7)
SREBP-SCAP complex does not move to the Golgi Mature SREBP is not released Therefore concentration in the nucleus decrease There is less binding to SRE Therefore gene expression is reduced This reduces cholesterol synthesis And down regulates the LDL receptor Plasma cholesterol levels increase
How n3 PUFA may increase FA oxidation (6)
In rodents n3 PUFA may act as Ligands for PPAR alpha
Which then induces peroxisome proliferation
Leading to increased FA oxidation
This leads to a reduction in plasma lipids
However in humans expression of PPARa is weaker
And humans do not undergo peroxisome proliferation
Diet heart hypothesis (3)
Dietary saturated fatty acids increase increases plasma LDL cholesterol
Increased cholesterol is a major risk factor for CVD
Reducing SFAs in the dirt will reduce the risk of developing CVD
Effects of cholesterol esterification on LDL receptor (3)
Prevents build up of free cholesterol
Which allows maturation of SREBP at endoplasmic reticulum
Which increases LDL receptor gene expression
Effects of changing diet and cholesterol levels in mice on SREBPs (6)
Mature form of SREBP-1c and 2 are decrease
Cholesterol lowering drugs results in SREBP2 going up
But SREBP-1c goes down
Fasting results in both going down
High carb low fat diet increased 1c four fold
But 2 only increases to pre fasted levels
Mensink 2003 carb replacement (4)
Replacing 1% carb in diet with:
SFA and trans fat increases cholesterol
Mono or poly decreases LDL cholesterol
How do dietary fats determine plasma lipoprotein concentrations (7)
LDL receptor regulates cholesterol uptake
Cholesterol ester is broken down to free cholesterol in lysosome
Accumulation of LDL in cell inhibits transcription of LDL receptor gene
This inhibits LDL uptake
Cholesterol accumulation also inhibit
HMGCoA reductase gene expression
Reduced de novo cholesterol synthesis
This further reducing intercellular cholesterol
SREBP isoforms and their transcriptional activity (4)
Changes SREBP-1c parallel those mRNA for lipogenic enzymes
This SREBP-1c may play an change important role in regulating FA synthesis
Changes in mature SREBP-2 parallel changes in mRNAs for cholesterol-synthesising enzymes and LDLr
Thus SREBP-2 may play an important row in regulating cholesterol metabolism
