lipid metabolism and pathways Flashcards
what are the biological functions of lipids
Essential components of cell membranes eg phospholipids, glycolipids and cholesterol
Inter and intra-cellular signalling events eg precursor of steroid hormones
Energy generation and fuel storage eg triglycerides
Metabolism eg bile acids
Consider dietary and endogenously produced lipids
what is the structure and biological functions of lipids
storage lipids (neutral) - triglycerides (glycerols and 3 FAs) Membrane lipids (polar) - phospholipids and glycolipids Steroids - cholesterol
what are triacyglycerides
Constitute 90% dietary lipids
Major form of metabolic energy storage in humans
Hydrophobic in nature
glycerol and fatty acids
how are triglycerides metabolised
Depending on metabolic requirement there are 2 major metabolic pathways
TGs broken into free fatty acids and glycerol. Oxidation of fatty acids in mitochondria to release energy as ATP
Synthesis of fatty acids from acetyl-CoA (joined to glycerol molecule for storage)
how are TGs oxidised
3 stages of achieve complete oxidation of fatty acids to CO2 and H2O
1 removal of glycerol and oxidation of long chain fatty acids to 2 carbon fragments in the form of acetyl-CoA, this is B oxidation
2 oxidation of acetyl-CoA to CO2 in the citric acid cycle
3 transfer of electrons from reduced electron carriers to mitochondrial respiratory chains
what is B-oxidation of fatty acids
attachment to Co-A
Occurs in mitochondria and peroxisomes
1 Fatty acids activated by attachment to coenzyme A in cytosol
2 transfer of acyl-groups across mitochondrial membrane (rate-limiting step)
how is CoA transported into the mitochondria
transported in via carnitine carrier protein into mitochondria and back out
how is acetyl-CoA generated
3 progressive oxidation of fatty acids by removal of 2 carbon units to form acetyl-CoA which enters the citric acid cycle
Each cycle shortens chain by 2C
1 acetyl-CoA formed, 1 FADH2 formed and 1 NADH formed
Used to generate energy for the cell
Whole process repeated until completely broken down into Acetyl-CoA
what is the step FAD to FADH2 responsible for
this step catalysed by a group of dehydrogenase isozymes, mutations in these can cause SIDS
what is fatty acid synthesis
Occurs mainly in liver and adipocytes
Long carbon chain molecules built up from 2 carbon units derived from acetyl-CoA
Occurs in the cytosol
But acetyl CoA is in the mitochondria
what is the citrate malate cycle
How acetyl-CoA gets out of the mitochondria
OAA + AcCoA = citrate
tricarboxylate transporter out d mitochondria
citrate (ATP-ADP and CoA-AcCoA) to OAA to malate to pyruvate and back to mitochondria via pyruvate transporter
what is fatty acid biosynthesis
Citrate>Acetyl-CoA>Malonyl CoA
Malonyl CoA and acetyl CoA both bind to fatty acid synthase
A series of condensation reactions involving malonyl CoA adds further C2 units
how is fatty acid oxidation and synthesis controlled
Rate limiting steps
B oxidation transfer of acyl-CoA into mitochondria
Fatty acid synthesis: formation of malonyl CoA from acetyl-CoA, catalysed by acetyl CoA carboxylase> subject to control by glucagon and insulin
what is cholesterol used for
Essential to life
Deposition in arteries associated with heart disease and stroke
In healthy organism, balance maintained between biosynthesis, utilisation and transport – keeping harmful deposition to minimum
what is the role of cholesterol and bile acids (salts)
The physiological roles of cholesterol include
Important component of biological membranes, precursor of steroid hormones and sources of bile acids
Bile acids are polar derivatives of cholesterol and aid in
Lipid deposition, lipid absorption and cholesterol excretion
what is the structure of cholesterol
Amphipathic lipid (-OH)(hydrophobic and hydrophilic portions)
Synthesised from acetyl-CoA and eliminated as bile acids
Storage is cholesterol ester
found in most tissues
Cholesterol acyltransferases eg Acyl-CoA cholesterol Acyltransferase (ACAT) catalyses formation of cholesterol esters
What is cholesterol biosynthesis
4 stages but only need to know major site of synthesis is the liver with lesser amounts made in intestine and adrenal cortex
AcCoA(C2)- HMG-CoA(C8)-(HMG-CoA reductase)- Melanovate (C6)- Squalene(C30) - Cholesterol (C27)
What does HMG-CoA reductase do
rate determining step cholesterol is feedback inhibitor mevalonate is feedback inhibitor target site for statin drugs also regulated by insulin/glucagon
how are lipids transported around the body
Bring dietary lipids to cells for energy production or storage
Move lipids from storage in adipose tissue for use in energy production
Provide lipids from the diet to cells for synthesising cell membranes
Carry cholesterol from peripheral tissues to the liver for excretion
how are lipids transported in the blood
Short chain fatty acids are transported bound to blood proteins like albumin
Bulk transport of neutral lipids, insoluble in water, require special carrier proteins known as lipoproteins
Neutral lipids carried in central core, outer layer of amphipathic phospholipids and cholesterol
Characteristics of major classes of lipoproteins
VLDL, IDL, LDL, HDL
Greatest amount of cholesterol carried by LDL
VLDL unload triacylglycerols at the tissues to become IDL to unload further lipids to become LDL
Classes of lipoproteins
Seen in the EM after negative staining Diameters (nm) Chylo 50-200 VLDL 28-70 LDL 20-25 HDL 8-11
Summary of lipid transport
Chylomicrons deliver dietary TGs to muscle and adipose tissue + dietary cholesterol to the liver
VLDL- transport endogenous TGs and cholesterol
LDL- transport cholesterol from liver to tissues
HDL- transport cholesterol to tissues to liver eg removing cholesterol from tissues (revere cholesterol transport)
how are lipids taken up by cells
Chylomicrons and VLDL particles give up lipid (TG) to tissues by action of tissue bound lipases
The liver recognises remnants of these particles by their ApoE content and takes them up for recycling
LDL particles contain ApoB-100 which is recognised by cell surface LDL receptors (LDLRs)
what does LDL uptake do
A source of cholesterol and ensures there is not too much in the blood
uptake of cholesterol results in decrease in cholesterol and LDLR synthesis
how are LDLR receptors regulated
expression of LDL receptors increased by SREBPs in response to low cholesterol
PCSK9 Bind to LDL receptor and once LDL and receptor in cell it targets it for degradation
Cellular cholesterol homeostasis
Proteins in cell membrane to allow cholesterol excretion, loaded on HDL for return to liver
SREBP exported to Golgi when cholesterol low, activation of SREBP increases HMGCR activity and expression of LDLR
