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    FA Desaturation

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    ololade
    This document summarizes key aspects of fatty acid desaturation and metabolism. It discusses how desaturase enzymes introduce cis double bonds into fatty acids in the endoplasmic reticulum. Unsaturated fatty acids have lower melting points than saturated fatty acids. The document also describes how animals require certain polyunsaturated fatty acids like linoleate and alpha-linolenate in their diets because they cannot synthesize double bonds in positions beyond carbon 6 counting from the methyl end. These essential fatty acids are precursors for signaling molecules like prostaglandins. The relationship between carbohydrate and fat metabolism is also summarized, where excess carbohydrates that cannot be stored as glycogen are converted to fatty acids.

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    FA Desaturation

    Uploaded by

    ololade
    34 views4 pages
    This document summarizes key aspects of fatty acid desaturation and metabolism. It discusses how desaturase enzymes introduce cis double bonds into fatty acids in the endoplasmic reticulum. Unsaturated fatty acids have lower melting points than saturated fatty acids. The document also describes how animals require certain polyunsaturated fatty acids like linoleate and alpha-linolenate in their diets because they cannot synthesize double bonds in positions beyond carbon 6 counting from the methyl end. These essential fatty acids are precursors for signaling molecules like prostaglandins. The relationship between carbohydrate and fat metabolism is also summarized, where excess carbohydrates that cannot be stored as glycogen are converted to fatty acids.

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    FA desaturation

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    This document summarizes key aspects of fatty acid desaturation and metabolism. It discusses how desaturase enzymes introduce cis double bonds into fatty acids in the endoplasmic reticulum. Unsaturated fatty acids have lower melting points than saturated fatty acids. The document also describes how animals require certain polyunsaturated fatty acids like linoleate and alpha-linolenate in their diets because they cannot synthesize double bonds in positions beyond carbon 6 counting from the methyl end. These essential fatty acids are precursors for signaling molecules like prostaglandins. The relationship between carbohydrate and fat metabolism is also summarized, where excess carbohydrates that cannot be stored as glycogen are converted to fatty acids.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    34 views4 pages

    FA Desaturation

    Uploaded by

    ololade
    This document summarizes key aspects of fatty acid desaturation and metabolism. It discusses how desaturase enzymes introduce cis double bonds into fatty acids in the endoplasmic reticulum. Unsaturated fatty acids have lower melting points than saturated fatty acids. The document also describes how animals require certain polyunsaturated fatty acids like linoleate and alpha-linolenate in their diets because they cannot synthesize double bonds in positions beyond carbon 6 counting from the methyl end. These essential fatty acids are precursors for signaling molecules like prostaglandins. The relationship between carbohydrate and fat metabolism is also summarized, where excess carbohydrates that cannot be stored as glycogen are converted to fatty acids.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 4

    Chem*3560 Lecture 22: Fatty acid desaturation

    Relationship of carbohydrate and fatty acid metabolism


    The fatty acid synthase multienzyme complex converts
    cytoplasmic acetyl CoA and malonyl CoA into the C16
    fatty acid, palmitate. Most animal fats and
    phospholipids lipids contain more C18 fatty acid such as
    stearate, while lipids in the nervous system can contain
    chains of C24 (nervonic acid) or longer. Additional
    elongation is carried out by the fatty acid elongase
    system.

    Elongase is a set of four more loosely associated


    enzymes on the endoplasmic reticulum membrane that
    act on acyl-CoA derivatives rather than acyl-ACP
    (Lehninger p.781). The individual enzymes make the
    elongation process less efficient than the fatty acid
    synthase complex.

    Fatty acid desaturation

    The other modification of fatty acid involves


    introduction of cis-double bonds. The double bonds
    introduced by dehydratase are trans-, so can't simply
    be left in place.

    Lipids that include unsaturated fatty acids with


    cis-double bonds have lower the melting points. In
    plants, unsaturated triacylglycerols are liquid oils rather
    that solid fats like animal triacylglycerols, which are
    predominantly made from saturated fatty acids. In
    animals, unsaturated fatty acids are used mostly in the
    phospholipids that make up membranes, and give the
    phospholipids the necessary degree of fluidity.

    Fatty acid desaturases belong to an unusual group of enzymes called mixed function oxidases.

    The term oxidase indicates that molecular O2 is the electron acceptor. However, removing 2 H• atoms
    from a substrate only consumes one of the two O atoms. To prevent the second O atom from making
    dangerous peroxides, a reducing agent such as NADPH is used to reduce the second O atom safely to
    H2 O. The term mixed function refers to the fact that each O atom of O2 takes a different reaction
    pathway (Lehninger p.781).
    The fatty acyl-CoA desaturase complex

    Fatty acid desaturase is a multienzyme complex containing the following components:

    The 9-desaturase is the substrate specific component that accepts a saturated 16 or 18 carbon
    acyl-CoA, and removes 2 H atoms to create a cis-double bond between C-9 and C-10 (i.e.
    bond 9 in the chain). The H atoms form H2 O using one of the O atoms of O2 . The other O
    atom is made safe by reduction using 2 electrons, one each from 2 molecules of cytochrome b5
    Fe 2+. Cytochrome b5 is an electron carrier related to cytochromes in mitochondrial electron
    transport, but has a specific role in desaturation reactions.

    Cytochrome b5 reductase recycles cytochrome b5 Fe 3+ back to the Fe2+ state. NADPH


    serves as the final reducing agent, and passes two electrons to an internally bound FAD, making
    FADH2 , and FADH2 reduces the cytochromes. Cytochrome b5 reductase is present in
    several desaturase complexes.

    A notation to describe unsaturated fatty acids

    The 9-desaturation product from the C18 fatty acid stearoyl-CoA is oleyl-CoA. Many of the possible
    unsaturated fatty acid have unique names, but a shorthand descriptive notation that describes fatty
    structures in an unambiguous way is often used (Lehninger p.781):

    oleate = ∆ 9)
    18:1 (∆
    „
    ~ „ location of the double bonds (cis unless otherwise specified)
    number of C number
    atoms in chain of double bonds
    Essential fatty acids in the diet

    Animals also possess a fatty acid 5/6-desaturase, but lack desaturase for higher numbered positions.
    The fatty acid arachidonate, 20:4 (∆ ∆ 5, 8, 11, 14) is specifically required as precursor for an important
    class of cellular signalling molecules called
    prostaglandins.

    Prostaglandins and other eicosanoids (from Greek


    icosa, 20) regulate contraction of smooth or
    involuntary muscles in bronchial passages, gut, and
    blood vessel walls, and a subgroup are involved in
    platelet activation (see Lehninger p.784-788 for
    interest, but they fall outside the scope of this course).

    In order to make arachidonate, animals must consume linoleate, 18:2 (∆ ∆ 9, 12) or α -linolenate ,
    18:3(∆ ∆ 9, 12, 15), which are present in plant materials and vegetable oils (so called polyunsaturated
    fatty acids ). Only plants possess the 12-desaturase and 15-desaturase enzymes, which act on
    esterified fatty acids in phospholipids (Lehninger p.782-784).

    When animals consume linoleate, their own enzymes can convert it to arachidonate in stepwise manner
    (Lehninger fig. 21-13)

    5/6-desaturase elongase system 5/6-desaturase


    linoleate → γ -linolenate → eicosatrienoate → arachidonate
    ∆ 6, 9, 12)
    18:3(∆ ∆ 6, 9, 12)
    18:3(∆ ∆ 8, 11, 14)
    20:3(∆ ∆ 5, 8, 11, 14)
    20:4(∆

    α -linolenate

    Double bonds produced by the desaturases are allylic, not conjugated. This means there is a single
    -CH2 - between sets of double bonded C atoms, and double bonds are spaced 3 apart. Any -CH2 -
    adjacent to a double bond is called an allylic carbon, and is unusually reactive towards O2 .

    Paints used to be made from linseed oil, which is rich in linoleate and linolenate. O2 reacts with and
    cross-links allylic C atoms in adjacent chains, so that the oil dries to a tough polymeric solid.
    Relationship between carbohydrate and fat metabolism

    In animals, there is no way to convert fats to sugars, since acetyl-CoA cannot be converted back into
    pyruvate. Fats can only be consumed for energy metabolism, and if energy metabolism consumes less
    fat that is produced, fat accumulates.

    On the other hand, sugars and other carbohydrates are easily converted to fat. A sugar or starch rich
    meal results in a large increase in blood glucose as the sugars are taken up by the digestive system.High
    blood glucose triggers insulin release, which stimulates cells to take up glucose from the blood. In
    peripheral tissues, glucose must be converted to glucose-6-phosphate by hexokinase. If
    glucose-6-phosphate exceeds requirments, because ATP demand is low and glycogen levels are
    already high, glucose-6-phosphate blocks further hexokinase activity by the product inhibition
    effect.

    Liver cells contain glucokinase or hexokinase D, which is the high KM isozyme and is unaffected by
    product inhibition. As a result, liver continues to incorporate glucose from the blood. Insulin also
    stimulates glycolysis in the liver, so that once glycogen levels are high, surplus glucose undergoes
    glycolysis. Pyuvate is converted to acetyl CoA and citrate. If the [ATP] / [ADP] ratio is high, isocitrate
    dehydrogenase activity will be low, so citrate spills over into the cytoplasm, and sets off the fatty acid
    biosynthesis process.

    Unused palmitoyl-CoA exerts end-product regulation of acetyl-CoA carboxylase, slowing down fatty
    acid biosynthesis. Unforunately this results in accumulation of excess cytoplasmic acetyl CoA, and that
    in turn becomes directed to the cholesterol biosynthesis pathway (for your interest, see Lehninger
    p.799-805, but the topic lies outside the scope of this course).

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