III. Metabolism Fatty Acid Catabolism

[Pages:51]Department of Chemistry and Biochemistry University of Lethbridge

Biochemistry 3300

III. Metabolism Fatty Acid Catabolism

Biochemistry 3300

Slide 1

Processing of Dietary Lipids in Vertebrates

Biochemistry 3300

Slide 2

Structure and Mechanism of Pancreatic Lipase

PDBBidio1cLhPeAmistry 3300

The enzymatic activity of pancreatic lipase is greatly increased by pancreatic colipase (1:1 complex)

The catlytic center is covered by a 25 residue helical 'lid'.

Binding to micelles causes structural changes: (1) 'lid' uncovers active site (2) 5 loop forms oxyanion hole

The active site contains a catalytic triad that closely resembles that in serine proteases.

Slide 3

Serine Proteases - Catalytic Mechanism

Catalytic triad Ser, His, Asp

Substrate Binding (peptide)

Transition State (1)

Transition State (2)

Biochemistry 3300

H2O

Substrate binding (water)

Covalently-bound intermediate

Slide 4

Serine Proteases - Catalytic Mechanism

Transition state has negative charge that is stabilized by a pair of mainchain amines

(the oxyanion hole)

Transition state stabilization within the oxyanion hole

Biochemistry 3300

Slide 5

Structure and Mechanism of Phospholipase A

Biochemistry 3300

Slide 6

Intestinal Fatty Acid-binding Protein

Inside the intestinal cells, fatty acids form complexes with intestinal fatty acid-binding protein (I-FABP).

Why?

To increase the effective solubility and to protect the cell from their detergent-like effects.

Biochemistry 3300

Slide 7

Mobilization of Stored Triacylglycerols

Neutral lipids are stored in adipocytes as lipid droplets

- core of sterol esters and triacylglycerols - exterior is phospholipid monolayer

Lipid droplet surface is coated with perilipins

- restricts access to droplet

Step 1

Hormones (epinephrine, glucagon) secreted due to low blood glucose levels activate adenylyl cyclase.

Biochemistry 3300

Slide 8

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