Lecture 15: Lipid metabolism Flashcards
What are the biological functions of lipids?
Cell membranes
Energy storage
Steroid hormones
Metabolism
What make up a triglyceride?
Glycerol + 3 FAs
What fats are for storage?
TGs
What fats are used for membranes?
Phospholipids - glycerophospholipids and sphingolipids
Glycolipids - sphingolipids
What make up a glycerophospholipid?
Glycerol + 2 FA + phosphate + alcohol
What make up a sphingolipid (phospholipid)?
Sphingosine + FA + phosphate + choline
What make up a sphingolipid (glycolipid)?
Sphingosine + FA + mono or oligosaccharide
What is beta-oxidation?
Oxidation of long chain fatty acids to 2 carbon fragments in the form of acetyl-CoA
Where does b-oxidation occur?
In the mitochondria and in peroxisome
How are fatty acids moved into the mitochondrial matrix?
Carnitine carrier protein - the acyl is transferred from the coenzyme-A to carnitine, this is transferred across the membrane into the matrix where it then detaches from the carnitine and bind to CoA present in the matrix.
Each transfer of FA requires carnitine palitoyl transferase (1 or 2)
Where is carnitine palmitoyl transferase 1 found?
Cytosol
Where is carnitine palmitoyl transferase 2 found?
Mitochondrial matrix
What is the rate limiting step of b-oxidation?
Transfer of acyl groups across the mitochondrial matrix
What are the three stages of b-oxidation?
1: FA activated by attachment of Coenzyme A
2: transfer of acyl across mitochondrial membrane
3: progressive oxidation FA by removal of 2 carbon units to form acetyl-coA (which enters citric acid cycle)
What three molecules are formed during each cycle of b-oxidation?
1 acetyl coA
1 FADH2
1 NADH
What is the first reaction for the removal of acetyl coA from fatty acyl-coA?
Fatty acyl CoA to trans-enoyl CoA
Enzyme = acyl-coA dehydrogenase
A mutation in which enzyme will cause SIDS?
Acyl-coA dehydrogenase
Where does fatty acid synthesis occur?
In the cytosol (mainly in the liver and adipocytes)
How does acetyl-coA get out of the mitochondria?
By the citrate malate cycle
Describe the citrate malate cycle.
OAA + acetyl-coA –> citrate
Citrate leaves the cell by tricarboxylate transporter
In the cytosol citrate is converted back to OAA and acetyl-coA
Acetyl-coA used for FA synthesis
OAA converted to malate then pyruvate and pyruvate is shuttled back into the mitochondria by the pyruvate transported
What is the rate limiting step of FA synthesis?
Carboxylation of acetyl-CoA to make malonyl-CoA
Catalysed by acetyl CoA carboxylase
In FA synthesis, what is acetyl CoA first converted into?
Malonyl-CoA
How is FA synthase regulated?
Malonyl-CoA and acetyl-CoA both bing to FA synthase
What type of reaction adds further C2 units in FA synthesis?
Condensation reactions
How is acetyl-CoA carboxylase regulated?
Subject to phosphorylation under the control of glucagon (inactivates) and insulin (activates)
What enzyme catalyses the formation of cholesterol esters?
Acyl-CoA Cholesterol Acyltransferase (ACAT)
How is cholesterol stored?
In the form of cholesterol esters
What are bile acids used for?
Lipid digestion
Lipid absorption
Cholesterol excretion
What is the rate limiting step of cholesterol synthesis?
Conversion of HMG-CoA to Mevalonate
Enzyme: HMG-CoA Reductase
Where is the major site of cholesterol synthesis?
Liver
some in intestine and adrenal cortex
What is the target for statins?
HMG-CoA reductase
How is HMG-CoA reductase regulated?
Both cholesterol and mevalonate are feedback inhibitors
What do chylomicrons transport?
Dietary TGs to muscle and adipose tissue and dietary cholesterol to the liver
What do VLDLs transport?
Endogenous TGs and cholesterol
What do LDLs transport?
Cholesterol from the liver to tissues
What do HDLs transport?
Cholesterol from tissues to liver
What are the two stages of dietary TG digestion?
1: emulsification by bile acids
2: hydrolysis by the enzyme pancreatic triacylglycerol lipase
What is PCSK9?
Binds to LDL receptors and cause their degradation
What is SREBP?
Increases expression of LDL receptors in response to low cholesterol
