Biosynthesis of Lipids Flashcards
Explain the process of acetyl-CoA formation and its transport to and from the mitochondria
Acetyl-CoA is formed in the mitochondria through pyruvate oxidation or catabolism of amino acid carbon skeletons.
a-CoA cannot diffuse through the inner mitochondrial membrane. It is transformed into citrate by reacting with oxaloacetate (citrate synthase). Citrate can be transported through the inner membrane by citrate transporter. a-CoA and oxaloacetate are regenerated in the cytosol by cleavage by citrate lyase.
Oxaloacetate, which facilitates transport of a-CoA, cannot pass through the mitochindrial membranes either. Malate dehydrogenase reduces oxaloacetate to malate. Malate can either be transported to the matrix through malate-a-ketoglutarate-transporter, or be oxidized to pyruvate by malic enzyme and enter mitochondria through pyruvate transporter.
Pyruvate is converted back to oxaloacetate by pyruvate carboxylase, and malate is converted to oxaloacetate by malate dehydrogenase.
List the enzymes involved in a-CoA transport in and out of the mitochondria and their function
Citrate synthase: converts a-CoA and oxaloacetate to citrate to be transported through the citrate transporter.
Citrate lyase: cleaves citrate to a-CoA and oxaloacetate in the cytosol.
Malate dehydrogenase: converts oxaloacetate to malate for transport into the mitochondria through the malate-a-Ketoglutarate transporter.
Also converts malate back into oxaloacetate when in the mitochondrial matrix.
Malic enzyme: converts malate into pyruvate for transport into the mitochindria through the pyruvate transporter.
Pyruvate decarboxylase: converts pyruvate into oxaloacetate.
Name the compunds in synthesis of triacylglyceror (TAG) and (glycerol)phospholipid from glucose and glycerol
Glucose is converted to dihydroxyacetonephosphate (DHAP) in glycolysis. Both DHAP and glycerol are converted to glycerol 3-phosphate.
Gly3P is converted to phosphatidic acid which can either make glycerophospholipid, or 1,2-diacylglycerol and ultimately TAG.
Explain the enzymatic steps from glycerol 3-phosphate to TAG
Two fatty acids are added to Gly3P by acyl transferases from activated fatty acids in two steps, forming phosphatidic acid. The fatty acids are activated with CoA by acyl-CoA synthetase.
Phosphatidic acid is converted to 1,2-diacylglycerol by phosphatidic acid phosphatase (lipin).
The last fatty acid is connected to 1,2-diacylglycerol by acyl transferase (same as first step), resulting in triacylglycerol.
Briefly explain the hormonal regulation of TAG synthesis
Insulin is secreted as a result of a surplus of energetic compunds (glucose, acetyl-CoA). This in turn increases the production of acetyl-CoA, fatty acids and TAG.
Glucagon and epinephrine, in addition to reducing glycolysis and increasing gluconeogenesis, stimulate lipolysis (production of glycerol and release of fatty acids from TAG) to provide energy in extrahepatic tissues from oxidation of fatty acids.
Name the different groups of glycerophospholipids
Phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, cardiolipin
What is the precursor for synthesis of the glycerophospholipids?
CDP-diacylglycerol
What are the two main pathways of (bacterial) phospholipid synthesis from CDP-diacylglycerol and their intermediates?
CDP-diacylglycerol can take pathways either to cardiolipin, or phosphatidylethanolamine.
The pathway to caridolipin goes as follows:
CDP-diacylglycerol -> phosphatidylglycerol 3-phosphate -> phosphatidylglycerol -> cardiolipin (from PG and CDP-DAG).
The pathway to phosphatidylethanolamine goes as follows:
CDP-diacylglycerol -> phosphatidylserine -> phosphatidylethanolamine -> phosphatidylcholine.
What are the two strategies for attaching the phospholipid head groups?
The attachment of head groups require activation by CDP.
The CDP can activate 1,2-diacylglycerol to CDP-diacylglycerol before attachment of the headgroup,
or the headgroup can be activated with CDP before attachment to 1,2-diacylglycerol.
The unactivated alcohol group of either 1,2-diacylglycerol or the headgroup beforms a nucleophilic attack on the CDP-activated phosphate group (carrying the head group).
Explain the Lands cycle
Remodeling of membrane phospholipids in mammals is performed through the Lands cycle.
The fatty acids of C2 is replaced in the Lands cycle. First they are removed through hydrolyzis by phospolipase A2 to create (1-acyl) lysophospholipids (lysophosphatidylcholine). The fatty acid is then replaced by lysophosphatidylcholine acyltransferases (LPCATs)
(Synthesis of sphingolipids and plasmalogens)
What are the four main steps of cholesterol synthesis?
1: Condensation of three acetate-units to mevalonate.
2: Convertion of mevalonate to activated isoprene.
3: Polymerization of 6 (5-carbon) isoprene units to linear squalene.
4: Cyclization of squalene to four rings, and a series of changes to form cholesterol
Explain the steps of mevalonate synthesis from acetyl-CoA
2 a-CoA units are condensed to acetoacetyl-CoA by thiolase. Another a-CoA is added by HMG-CoA synthase to form HMG-CoA (b-Hydroxy-b-methylglutaryl-CoA).
2 NADPH are used to convert HMG-CoA to mevalonate by HMG-CoA reductase.
Explain the steps from mevalonate to activated isoprene
Short:
Mevalonate accepts three phosphate groups from three ATPs.
Decarboxylation and hydrolysis produces the first activated isoprene unit.
Isomerization of this unit produced the second activated isoprene unit.
Long:
Mevalonate and phosphate produces 3-phospho-5pyrophosphomevlonate through a series of steps. Both the phosphate and carboxyl group of this intermediate leave, resulting in (delta3-)isopentenyl pyrophosphate, the first activated isoprene Isomerization of this unit produces dimethylallyl pyrophosphate, the second activated isoprene unit.
Explain the steps from activated isporene to squalene
Six activated isoprene units are condensed into squalene.
Firstly two units (isopentenyl pyrophosphate and dimethylallyl pyrophosphate) condense (head to tail) to form geranyl pyrophospate. Another isoprene unit (isopentenyl pyrophosphate) condense (head to tail) with geranyl pyrophosphate to form farnesyl pyrophosphate. Two molecules of farnesyl pyrophosphate condense (head to head) to form squalene.
