Lecture 20- Lipogenesis

Lipogenesis

this is the metabolic formation of fatty acids (usually Palmitate) but then can be customized to other fatty acids or lipids

Cytosol

The first part of fatty acid synthesis is to gather Acetyl CoA and NADPH into the ___________, because that is where fatty acid syntehsis takes place

Acetyl CoA

this ingredient for fatty acid synthesis can't pass through the membrane so it is converted to citrate before being transported into the cytosol from the mitochondria

Citrate lyase

When citrate is transported into the cytosol, it is cleaved by this enzyme, which requires ATP, and then it can be used for lipid synthesis because it is now Acetyl CoA and oxaloacetate

Malate

To "clean up" the extra oxaloacetate, one way it can be transported back into the mitochondria is by converting to ____________, and then it goes through a transporter, but this is a minor pathway

NADP+, NADPH

the main way oxaloacetate is cleaned up is by converting it malate, and then to pyruvate and CO2, while also reducing a molecule of ___________ to _____________

Pentose Phosphate Pathway

while some NADPH is obtained through the conversion of malate to pyruvate, the bulk of the NADPH is obtained through this

Malonyl-CoA

this is formed from acetyl CoA and bicarbonate (essentially adding a carbon to acetyl CoA), must be used for lipogenesis

Acetyl-CoA carboxylase

this is a highly regulated enzyme for Lipogenesis that converts Acetyl CoA to Malonyl CoA

Fatty Acid Synthase

this is a huge molecule (Machine) that is a single polypeptide with multiple enzyme active sites, and helps catalyze the process of lipogenesis

Acyl Carrier Protein

this is the protein that shuttles the growing chain from one active site to another on Fatty Acid Synthase during the 4 step reaction of lipogenesis

Acetyl-CoA, Malonyl CoA

The first two carbons of fatty acid synthesis comes from _______-_____, while the rest of the carbons come from __________ _____

Condensation

this first step of lipogenesis couples the decarboxylation of malonyl-CoA to the attachment of two carbons from malonyl CoA to the fatty acid complex (acetyl CoA at first, but the growing fatty acid after)

1st Reduction

this second step of lipogenesis reduces the keto group to an alcohol, coupled to the oxidation of NADPH to NADP+

Dehydration

this 3rd step of lipogenesis takes out water and creates a double bond between 2nd and 3rd carbon

2nd reduction

this 4th step of lipogenesis reduces the double bond coupled to the oxidation of NADPH to NADP+

Moved

Before adding another malonyl CoA to the growing fatty acid chain, the complex must be ______________ by ACP to the proper active site on Fatty Acid Synthase

Palmitate

The synthesis of fatty acids by fatty acid synthase ends with the generation of this specific fatty acid

7 ATP

How many ATP are used to generate palmitate? (from converting acetyl CoA to malonyl CoA)

14 NADPH

How many NADPH are used to generate palmitate?

ER, Mitochondria

elongation systems in these organelles can create longer fatty acids besides Palmitate, but they are done by those systems and not by fatty acid synthase

Fatty Acyl-CoA desaturase

this enzyme in animals can unsaturate one bond to a double bond in a fatty acid synthesized by using cytochrome B and NADPH

Polyunsaturated Fatty Acids

these are essential fatty acids because humans cannot make them, so we must get them from plants or diet because they are important for membrane fluidity and signaling lipids

Citrate

this allosterically activates Acetyl-CoA carboxylase, meaning that when it binds, it helps activate Lipogenesis (especially when ATP is high)

Glucagon, Epinephrine

these two hormones inhibit Acetyl CoA carboxylase

Palmitoyl-CoA

this causes feedback inhiibtion for Acetyl CoA carboxylase

Malonyl-CoA

this inhibits fatty acid import to the mitochondria, making it so that the fatty acids made in the cytosol are not immediately metabolized in the mitochondria

Phosphatidic Acid

this is a precursor to Triacylglycero and Glycerophospholipids, and this is what most fatty acids are added to

Glycerol-3 Phosphate

this is important for the synthesis of phosphatidic acid, and this can be made from DHAP by siphoning it off from glycolysis

DHAP

most glycerol-3 phosphate can be made from this molecule which is siphoned off from glycolysis

Glycerol Kinase

a minor pathway from glycerol 3 phosphate is by phosphorylating it directly from ATP with this enzyme

CoA

The fatty acids attached to phosphotatidic acid need to be joined with thsi first before being attached, and then this is released

Lipin

this is highly regulated and can help convert phosphatidic acid to Triacylglycerol, and dephosphorylates phosphatidic aci to 1,2 diacylglycerol, before adding the 3rd fatty acid

2

How many strategies are there for forming the phosphodiester bond of the head group from phosphatidic acid/diaclylglyerol to a phospholipid?

CTP

when starting with Phosphatidic acid, it uses ______ to phosphorylate the lipid, which eventually forms the phosphodiester bond

Alcohol

when starting with diacylglycerol, it uses CTP to phosphorylate the lipid, but also uses this (on diacylglycerol) to attach the phosphate and forms the diester bond

Palmitate, Serine, NADPH, Other Fatty Acid

TO make sphingolipids, you need these 4 things to synthesize it

Amide linkage

Sphingolipids are different from phospholipids because the type of bond between the phosphate is linked through this

UTP

when adding head groups to Sphingolipids, they use this to phosphorylate the head group