fatty acids and terpenoids

what are lipids and what are the two main classes of lipids (based on how they are derived)

biological molecules soluble in organic non-aqueous solvents

fatty acid derived lipids (C2 units)

terpenoid lipids (C5 units)

what is a fatty acid?

long chain carboxylic acids, often multiples of C2

describe triacylglycerols

three fatty acids ester bonded with gycerol alcohol groups

main use as storage molecule

lack of charged head group allows dense packing

describe glycerophospholipids

glycerol-3-phosphate with 2 ester bonded FAs

how are fatty acids transported?

via serum albumin

how are fatty acids activated?

• FA attacks ATP to form an anhydride, where its acyl group is attached to AMP, and pyrophosphate leaves

• CoA comes in and releases AMP by bonding with the terminal carbon of the fatty acid

• forming acylCoA, which is active since it can now be oxidised

describe the beta degradation of fatty acids

• FAD oxidises fatty acyl CoA into enoyl-CoA

• this has resonance structures, where beta carbon is electrophilic, and attacked by water to make alcohol

• NAD+ acts as hydride acceptor, making beta carbon into carbonyl

• CoASH attacks beta carbon, causing release of acetylCoA and a fatty acylCoA that is shorter by 2 carbon atoms

special reactions are used to deal with unsaturated positions or uneven chain lengths or branching

describe fatty acid biosynthesis

• occurs in cytoplasm

• C2 unit (malonyl) is added onto fatty acyl ACP to make ketoacylACP

• keto group is reduced into alcohol (hydroxyacylACP)

• alcohol group is dehydrated to make a double bond

• double bond is reduced to make fatty acyl ACP (n+2)

ACP is acyl carrier protein. all synthesis steps occur on this protein, while all degradation steps occur on CoA.

to make fatty acids, the first step required the C2 unit donor malonyl CoA. describe how this is made.

carboxylation of biotin-enzyme coupled withATP hydrolysis.

then substitute biotin-enzyme with acetyl CoA. this means youve ultimately just carboxylated acetyl CoA

driven by ATP

note that malonyl CoA has 3 carbon atoms

describe Biotin-dependent carboxylase enzymes (such as acetyl CoA carboxylase)

• two active sites, BC= biotin Carboxylase, CT= carboxyl transferase

• BCCP= biotin carboxyl carrier protein

• bound to BCCP is a lysine attached to a biotin head molecule

• the lysine acts as a flexible arm, can swing the biotin between active sites

• tasnlaocation of biotin between active site has a distance of 55-85A

describe how the enzyme acetyl CoA carboxylase uses bccp

active site 1:

• brings together carbonate (HCO3^- ) and ATP

• carbonate fuses to phosphate of ATP, which naturally falls apart into CO2 (which is trapped in enzyme due to crowding) and phosphate group

• phosphate acts as a base, activates biotin to act as a nucleophile which accepts CO2

swing into active site 2:

• CO2 released

• nucleophilic biotin deprotonates 2C unit

• 2C unit now bonds with CO2 to make malonyl CoA

once malonyl is transferred from CoA to ACP using MAT enzyme, what happens?

malonyl is decarboxylated to provide nucleophilic carbon which attacks a carbonyl group from an enzyme (KS which has a cys residue bound to acetate via S)

what is the function of desaturase enzymes?

to make unsaturated fatty acids

compare the C2 (ketoacyl) building blocks we’ve just discussed to C5 building block

C5 building blocks are isoprene, mostly branched or cyclic products while ketoacyl blocks make mostly linear products

C-C elongation of 2C units uses carbanion chemistry, while elongation of 5C units uses carbocation based chemistry

describe hyperconjugation

the overlap of a p orbital on a carbocation with a neighbouring molecular orbital, like a C-H or C-C bond

stabilises the carbocation

describe the ranges of terpenoids

very prominent in plant metabolism, over 85k compounds, used in fragrances, hormones and toxins

how is diversity introduced to terpenoids?

by using different numbers of isoprene units as well as stopping chain elongation to allow folding

why are C5 units branched?

allow tertiary carbocation formation

IPP isomerase enzyme. gives proton to C=C to form carbocation

should learn the ways in which tertiary carbocation is formed from the diagram

describe how a prenyltransferase attaches DMAPP to IPP

• pyrophosphate of DMAPP leaves via sn1, making allylic carbocation (+ charge near C=C) which has resonance stabilisation

• IPP is placed near carbocation, which is attacked by its electron rich C=C bond to make ternary carbocation

• proton eleminated by PPi which acts as base

• produces GPP, which acts similar to DMAPP, meaning the cycle can occur again with GPP used instead of DMAPP, thus chain elongates

magnesium required to allow PPi to leave at the start

what class of enzymes are responsible for the variety of terpenes?

terpene cyclases, which catalyse initial carbocation formation and substrate folding

small changes in their active site alter outcome of terpene