Lipid-2b

Classification Metabolism

Classification
Fatty acids Triacylglycerols Phosphoglycerides Sphingolipids Steroids

1. Fatty acid As major components of lipid molecules (triglycerides, phospholipids, sphinomyelin) Precursors to other molecules (prostaglandins) Provide energy (through oxidation processes) Industrial uses (soaps, etc)

1. Fatty acid

1. Fatty acid

Mostly have 14-20 carbons Even number of carbons Two numbers m:n m = number of carbons n = number of C=C bonds Double bonds are mostly cis

2. Triglycerides

1CH 2

OH

| 2CH OH | 3CH 2 OH Glycerol

Fat storage in adipocytes causes type-2 diabetes and resistin aggravates it.

3. Phosphoglycerides (Glycerophospholipid or Phospholipid)

Phospholipases
1CH 2

OH

| 2CH OH | 3CH 2 OH Glycerol

Degrade phospholipids Present in snake venoms Cause inflammation, fever, headache

4. Sphingolipids

-Derivatives of Sphingosine and Dihydrosphingosine -major components of membrane -Functions: -Cell-cell recognition -Tissue immunity -Impulse transmission

5. Steroids

Steroids stem from a single template

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Lipid-Linked protein
Lipids and proteins covalently interact to form lipid-linked proteins Prenylated; Fatty acetylated; Glycoinositol phospholipids

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Lipoproteins
Proteins and lipids non-covalently interact to form lipoproteins

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What is this?

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Lipid metabolism
* 1. Fatty acid degradation -oxidation Ketone body 2. Fatty acid biosynthesis 3. Triacylglycerol biosynthesis * 4. Phospholipid degradation 5. Cholesterol biosynthesis

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1. Fatty acid degradation: -oxidation Most fatty acids are degraded to form acetyl-CoA within mitochondria in a process called -oxidation Production of ATP to provide energy (resulted from oxidation of acetyl-CoA via citric acid cycle) Process found in all living organisms

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Acyl-CoA Acetyl-CoA
A Key molecule in lipid metabolism Acyl-CoA: fatty acid + Co-A Acetyl-CoA: acetyl form of Co-A
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Acyl-CoA reacts with carnitine to form acylcarnitine which can then be transported across the inner membrane of mitochondria and is subsequently recovered as acyl-CoA
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The -oxidation of acyl-CoA molecules include four reactions that occur in the mitochondria. Each cycle of reactions forms acetyl-CoA and acyl-CoA thats shorter by two carbons

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 Most acetyl-CoA produced from fatty acid degradation is used in citric acid cycle to generated energy Excess acetyl-CoA is converted to ketone bodies (acetoacetate, b-hydroxybutyrate and acetone) in a process called ketogenesis. Occurs in liver mitochondria

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Several tissues and organs (cardiac and skeletal muscles, brain) use ketone bodies to 23 generate energy by converting them back to acetyl-CoA

2. Fatty acid biosynthesis

A mean by which energy is stored Occurs within cytoplasm of most animal cells. However, liver is the major site for this process Overall reaction (palmitic acid):

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Desaturation of fatty acids

Saturated fatty acids can be desaturated

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Glucose

Glycerol

3. Triacylglycerol biosynthesis Even if you do not take a lot of fatty food, triglycerides can be synthesized from glucose

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4. Phospholipid degradation

Phospholipase A2

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Phospholipid digestion by Phospholipase A2 (PLA2)

Phospholipase A2 cuts a phospholipid and releases a fatty acid

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Phospholipase A2 (PLA2) properties

1 MiPLA1 MiPLA2 MiPLA3 MiPLA4 NLLQFRKMIK NLYQFRKMIK NLLQFRKMIK NLLQFRNMIK 71 NTYAYDCTKG NTYSYDCTDG NTYAYDCTDG NTYSYDCTDG 11 CTVPGREPLV CTIPGREPLL CTIPGIEPLL CTIPGREPLL 81 KITCNDQKDK KLTCNDQKDK KLTCNDQKDK KLTCNDQNDK 21 AFTDYGCYCG AFTDYGCYCG AFSNYGCYCG AFSNYGCYCG 91 CKLFICNCDR CKLFICNCDR CKLFICNCDR CKLFICNCDR 31 KGGSGTPVDE KGGSGTPVDE KGGSGTPVDE KGGSGTPVDE 101 TAAMCFAKAR TAAMCFAKAP TAAMCFAKAP TAAMCFAKAP 41 LDRCCQTHDN LDRCCQTHDN LDRCCQTHDY LDRCCQTHDN 111 YIEANNHIDP YIEANNHIDP YKEENNRIDA YNEAYNHFNR 51 CYDKAEKLPE CYDKAEKLPE CYDKAKIHPE CYDKAEKLPE 121 KRCK NRCK SNCK QLCK 61 CKGILSRPYV CKGILSGPYV CKGILSGPSF CKGILSGPYV

MiPLA1 MiPLA2 MiPLA3 MiPLA4

Hydrolytic activity
900 800 700 600 500 400 300 200 100 0
MiPLA1 2 3 4

Dark urine induction

0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 0
MiPLA1 2 3 4

Prothrombin time assay Muscle necrosis assay

160 140 120 100 80 60 40 20 0
Control MiPLA1 2 3 4

2000

1800 1600 1400 1200 1000 800 600 400 200 0

Control MiPLA1 2 3 4

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5. Cholesterol biosynthesis

From acetyl-CoA, steroids are synthesized

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From acetyl-CoA, steroids are synthesized

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