{"id":1842,"date":"2020-08-18T13:26:45","date_gmt":"2020-08-18T13:26:45","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-palmitate\/"},"modified":"2022-04-17T14:33:24","modified_gmt":"2022-04-17T12:33:24","slug":"synthesis-of-palmitate","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-palmitate\/","title":{"rendered":"Synthesis of Palmitate"},"content":{"rendered":"\n

Palmitate is a 16 carbon atom containing a chain of Acetyl-Coa and Malonyl-Coa. The capacity of mitochondrial production is the palmitate with its 16C atoms. Any other fatty acid is elongated, the mitochondria can only synthesize palmitate. <\/div><\/p>\n\n\n\n

Generation of Malonyl-Coa for the fatty acid synthesis<\/h2>\n<\/span>\n\n\n

Production of the Malony-Coa happens via Acetyl-CoA Carboxylase enzyme (ACC – Synthesis of Malonyl-CoA<\/a>). The synthesis requires a high energy state, which is generated by the ATP excess by the TCA cycle in the mitochondria (Figure 1.)<\/p>\n\n\n\n

The “production” of Malonyl-CoA starts in the mitochondria with the excess amount of Citrate from the TCA cycle.<\/p>\n\n\n\n

\"\"<\/a>
Figure 1. Production of the Malonyl-CoA in the cytosol<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

Citrate is transported<\/strong> into the cytosol through the citrate shuttle<\/strong>. In the cytosol, citrate changes back to Acetyl-CoA in an ATP-dependent process.<\/p>\n\n\n\n

Acetyl-CoA is being used by the ACC enzyme in the second enzymatic step of the carboxylase reaction, followed by the production of the Malonyl-Coa molecule.

The 3C atom-containing molecule the fatty acid synthesis can be initiated now. <\/p>\n\n\n<\/span>\n

Fatty acid synthase<\/h2>\n<\/span>\n\n\n

Fatty acid synthase is a dimeric, multifunctional enzyme. Each monomer is a multi-catalytic polypeptide with seven different enzymatic activities.<\/p>\n\n\n\n

Several domains are involved in the enzymatic activity, responsible for the binding of acetyl and malonyl-CoA, structure clarifying by the second domain, and the splicing by the third domain which is a thioesterase (Figure 1<\/strong>).<\/p>\n\n\n\n

\"\"<\/a>
Figure 2. Fatty acid synthase with the three domains<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

Domain I<\/strong>
AT<\/strong> – Acetyltransferase
MT<\/strong> – Malonyl transferase
CE<\/strong> – Condensing enzyme (Ketoacyl synthase)<\/p>\n\n\n\n

Domain II<\/strong>
KR<\/strong> – Ketoacyl reductase
DH<\/strong> – Hydratase “dehydration”
ER<\/strong> – Enoyl reductase
ACP<\/strong> – Acyl-carrier protein<\/p>\n\n\n\n

Domain III<\/strong><\/p>\n\n\n\n

TE <\/strong>– Thioesterase<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

<\/p>\n\n\n\n

\"\"<\/a>
Figure 3. Synthesis of palmitate<\/strong><\/figcaption><\/figure><\/div>\n\n\n<\/span>\n

Steps of the synthesis<\/h3>\n<\/span>\n\n\n
  1. transfer of acetate from acetyl-CoA to the -SH group of Acyl-carrier-protein (ACP)<\/li>
  2. transfer of malonyl unit from malonyl CoA to ACP<\/li>
  3. acetyl group on a cysteine residue condenses with the malonyl group on ACP by condensation enzyme (CE) (Figure 3<\/strong>)<\/li><\/ol>\n\n\n\n
    \"\"<\/a>
    Figure 4. Synthesis of palmitate<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

    <\/p>\n\n\n\n

    <\/p>\n\n\n\n

    4. \u03b2-ketoacyl-ACP is reduced to \u03b2-hydroxyacyl-ACP using NADPH as the electron donor by 3-Ketoacyl<\/strong> ACP reductase<\/strong> (KR<\/strong>)<\/p>\n\n\n\n

    5. \u03b2-hydroxy acyl-ACP is dehydrated<\/strong> to an enoyl-ACP by 3-Hydroxyacyl-ACP dehydratase<\/strong> (DH<\/strong>)<\/p>\n\n\n\n

    6. enoyl<\/strong>-ACP reductase<\/strong> (ER<\/strong>) using the second NADPH as a reductant (resulting in 4C butyryl-CoA) (Figure <\/strong>4). <\/p>\n\n\n\n

    A 4C unit is moved to the cysteine residue, a new malonyl CoA attaches to ACP, and another round started six more reaction cycles to produce palmitoyl-S-ACP.<\/p>\n\n\n\n

    \"\"<\/a>
    Figure 5. Synthesis of palmitate<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

    Palmitoyl thioesterase (TE<\/strong>) cleaves the thioester bond, releasing a fully saturated molecule of Palmitate (C16) (Figure 5).<\/p>\n\n\n\n

    \u201cTake home\u201d reactions:<\/strong><\/p>\n\n\n\n

    1. Activation + condensation (CE)<\/strong><\/li>
    2. Reduction (KR)<\/strong><\/li>
    3. Dehydration (DH)<\/strong><\/li>
    4. Reduction (ER)<\/strong><\/li><\/ol>\n\n\n<\/span>\n

      References<\/h2>\n<\/span>\n\n\n

      Snider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n<\/span>

      Generation of Malonyl-Coa for the fatty acid synthesis<\/h2>

      Fatty acid synthase<\/h2>

      Steps of the synthesis<\/h3>

      References<\/h2><\/div>","protected":false},"excerpt":{"rendered":"

      Generation of Malonyl-Coa for the fatty acid synthesis Production of the Malony-Coa happens via Acetyl-CoA Carboxylase enzyme (ACC – Synthesis of Malonyl-CoA). The synthesis requires a high energy state, which is generated by the ATP excess by the TCA cycle in the mitochondria (Figure 1.) The “production” of Malonyl-CoA starts in the mitochondria with the […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1712,"menu_order":5,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1842","page","type-page","status-publish","hentry"],"yoast_head":"\nSynthesis of Palmitate – Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-palmitate\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" 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