DM DLA 11: Fatty Acid Synthesis and Regulation

What are the 5 precursors for Fatty acid synthesis?

1- Acetyl CoA 2- CoA (panthothenic acid) 3- ATP 4- NADPH 5- Co2

What are the steps involved in the de novo synthesis of Fatty acids (Palmitate) from Acetyl CoA?

1- Acetyl CoA --> Malonyl CoA - via Acetyl CoA carboxylase 2- Synthesis of Palmitate - via Fatty acid synthase 3- Elongation of Palmitate - via Elongases 4- Desaturation - via Desaturases

What are the 3 main sources of Fatty acids? - what form of FA do they release into circulation respectively?

1- Diet - TAGs (packaged in chylmicrons) --> circulation) 2- Adipose tissue - Free fatty acids into circulation 3- Fatty acid biosynthesis - VLDLs into circulation

The overall synthesis of Palmitate from Acetyl CoA requires .... and .....?

ATPs NADPH

In the first Step of Fatty acid synthesis the Acyl carrier protein domain (ACP-SH) binds the .... group of Acetyl CoA? From then on ..... is used for chain elongation (but it can only react with the free ACP-SH)?

Acetyl Malonyl CoA •Hence the acetyl group is transferred to the SH group of the holding domain and now malonyl ACP can be formed from malonyl CoA

..... formed in mitochondria cannot cross the mitochondrial membrane into the cytosol ?- it thus has to be converted to ....?- at high levels it can then leave the cytosol

Acetyl CoA Citrate •At very high citrate levels, citrate leaves into the cytosol

Once inside the mitochondria The enzyme ..... uses Citrate in cytosol to form .... and .....?

Acetyl CoA OAA

...... and ...... when acted by the enzyme ..... form Citrate which can then enter the mitochondria?

Acetyl CoA OAA Citrate Synthase

The first committed step (ie rate limiting enzyme) of Fatty acid synthesis is catalyzed by the enzyme ....?

Acetyl CoA carboxylase (ACC)

Practice Q1

Ans: E

Acetyl CoA carboxylase contains .... and adds a .... to the methyl end of acetyl CoA, resulting in a carboxyl group of malonyl CoA? The reaction requires ..... per malonyl CoA formed?

Biotin Co2 1 ATP

Natural Unsaturated fatty acids are in .... configuration which introduce ...... into the structure? Natural Unsaturated fatty acids have double bonds that are usually .... carbons apart?

Cis Kinks 3 •Trans-fatty acids are mostly artificially formed

What is an example of an Activator of Fatty acid synthesis ? Inhibitor?

Citrate Long chain Fatty Acyl CoA (inhibits acetyl CoA carboxylase)

Fatty acid synthesis occurs in the .... of the cell? It occurs in the ..... state in the ....?

Cytosol Well-fed Liver

The multifunctional FAS enzyme exists as a .... in humans? It catalyzes the reactions whereby two carbon units from .... are linked together, ultimately to form ......? .... upregulates the amount of FAS enzyme expressed?

Dimer Malonyl CoA Palmitoyl CoA Insulin

Free fatty acids have detergent character and they are ..... in TAGs, cholesteryl ester or polar membrane lipids?

Esterified •> 90% of FAs in plasma as fatty acid esters (TAGs, cholesteryl esters, phospholipids) in circulating lipoproteins.

Acetyl-CoA is a key intermediate between ... and ... metabolism ?

Fat Carbohydrate

Fatty acids are Amphipathic - meaning that they have a ..... and ..... regions?

Hydrophilic Hydrophobic

The Major site of biosynthesis of fatty acids is the ..... and ...... gland? The minor site is the ....?

Liver Lactating mammary gland Adipose tissue •Liver: reduce high blood glucose levels, form palmitate and TAGs which are then released into the blood for eventual storage in fat cells. •Mammary gland: to provide FA for milk

..... are the fuel for Fatty acid synthase? The ... of the carboxyl-group of malonyl-ACP allows ..... with the group bound to the holding protein?

Malonyl CoA Decarboxylation Condensation •In general, a 3-ketoacyl-ACP is formed •NADPH is used to reduce to 3-hydroxy-acyl ACP.

The NADPH is required for Fatty acid synthesis to provide ...... ? What are the 2 sources of NADPH for fatty acid synthesis?

Reducing equivalents 1- Pentose Phosphate Pathway (PPP) - Major pathway 2- Malic enzyme (NADP+ dependent malate dehydrogenase

Fatty acids without double bonds are known as .... fatty acids? Fatty acids with one or more double bonds are known as .... fatty acids?

Saturated Unsaturated

Free Fatty acids are ...... and are transported in association with ..... in circulation?

Unesterified Albumin