Fatty Acid biosynthesis Flashcards
fatty acids
Consists of a hydrophobic hydrocarbon chain with a terminal carboxyl group
longer chain length = more insoluble in water
Fatty acids are usually esterified such as in the form of triacylglycerols. Plasma fatty acids are transported by serum albumin
Fatty acids are also structural components of membrane lipids, precursors of the hormone-like prostaglandins. They can also be conjugated on proteins.
hydrophobic carbon chain
hydrophilic carboxyl group (ionized @ pH7)
Saturated vs unsaturated fatty acids
- unsaturated: double bonds (usually in cis, causing kink)
- double bonds decrease melting temp of fatty acid
- membrane lipids: contain long chain fatty acids (16C or more), presence of double bonds in some FAs helps maintain membrane fluidity.
naming fatty acids
A.
- start numbering C at carboxyl carbon
- number before colon: C
- number ater: numbers and position of double bonds (20:4 (5,8,11,14)
B. The carbon atoms are numbered beginning with the second carbon as alpha , beta, gamma… The carbon of the terminal methyl group is called the omega-carbon regardless of chain length. The double bonds in a fatty acid can also be counted beginning at the omega-end.
linoleic acid and linolenic acid
(w-6) linoleic acid
(w-3) linolenic acid
-two dietary essential fatty acids because human cells do not have enzymes to introduce double bonds between carbon 9 and the w (omega) end of fatty acids.
Linoleic acid is the precursor of arachidonic acid, the substrate for prostaglandin synthesis.
Linolenic acid is the precursor of other w-3 fatty acids important for growth and development.
w=omega
important functions of fatty acids
Major hydrophobic components of all cell membranes
Major storage form of metabolic energy, 70-80% of caloric reserve is triacylglycerols
Essential precursors for the eicosanoids (paracrine hormones: prostaglandins, leukotrienes, thromboxanes)
Major sources of fatty acids
Biosynthesis from small molecule intermediates derived from metabolic breakdown of sugars, amino acids and fats
Diet essential fatty acids (Linoleic and linolenic acid)
Linoleic acid (the precursor of arachidonic acid, the substrate for
prostaglandin synthesis)
Linolenic acid (the precursor of other w-3 fatty acids important for
growth and development)
Bonds and melting temp
Addition of double bonds decreases melting temp.
Increasing chain length increases melting temp.
rate limiting step in FA biosynthesis
-formation of malonyl CoA (using acetyl CoA carboxylase)
long chain fatty acyl coA inhibits inactive dimer of Acetyl coa carboxylase
Citrate encourages Acetyl CoA carboxylase (inactive to active polymer)
conversion of malonyl CoA to FA
Malonyl CoA is the substrate for Fatty Acid Synthase (FAS)
FAS (multifunctional enzyme):
- seven enzyme activities
- Acyl Carrier Protein (ACP)
- performs all the steps to convert malonyl CoA to a fatty acid
The fatty acid molecule is synthesized 2 carbons at a time (four step repeating cycle with the extension of 2 carbons/cycle)
The product of FAS is palmitic acid (16:0). Palmitate is released from FAS by the palmitoyl thioesterase activity and can then undergo separate elongation and/or desaturation to yield other fatty acid molecules.
First 2 C come from
acetyl CoA (then malonyl CoA additions), becomes methyl end
malonyl coA as substrate to add 2C at a time
Final: palmitate 7 rounds (2C added each time, plus the 2 from acetyl coA at beginning)
fatty acid elongation and desaturation
Elongation of palmitate occurs in mitochondria and endoplasmic reticulum (ER), a family of enzymes designated Fatty Acid Elongases catalyze the initial condensation step for elongation of saturated or polyunsaturated fatty acids.
Formation of a double bond in a fatty acid involves ER membrane proteins in mammalian cells, termed mixed-function oxidases. Mammalian cells are unable to produce double bonds between carbon 9 and the w-end of the chain. Thus some polyunsaturated fatty acids are dietary essentials, e.g., linoleic acid.
Metabolic regulation FA synthesis: diet and metabolic conditions
High carbohydrate leads to high pyruvate and acetyl CoA levels in the mitochondrion, which favors production and translocation of citrate from the mitochondrion to the cytosol, thus stimulating fatty acid synthesis.
High fat/low carbohydrate leads to low pyruvate flux in the mitochondrion. Fat metabolism is associated with elevated acyl CoA in the cytoplasm. Both conditions reduce fatty acid biosynthesis.
Hormonal environment: high insulin favors lipogenesis (fatty acid biosynthesis); high glucagon favors lipolysis (beta-oxidation) and decreased fatty acid biosynthesis.
regulation of FA synthesis:
long term reg by gene transcription
Prolonged consumption of a diet containing excess calories causes an increase in acetyl CoA carboxylase and fatty acid synthase synthesis; in contrast, fasting causes a reduction of acetyl CoA carboxylase and fatty acid synthase.
Citrate (short term regulation of FA biosynth)
Availability of cytosolic citrate determines the amount of acetyl CoA available for fatty acid synthesis. It also helps produce NADPH for the reducing equivalents used in the reactions.
Citrate can also activate acetyl CoA carboxylase by causing polymerization of the enzyme (conformational change) and increasing the Vmax.
Palmitoyl CoA
Acts as an inhibitor of acetyl CoA carboxylase.
Cytosolic levels are elevated during starvation or on high fat diets.
