Oxidation of Lipids I

Suaib Luqman

Objectives

v To understand the digestion, absorption and secretion of lipids or fats
v How dilapidation of lipids or fats takes place

Concept Map

Description

The main lipids of the body are basically triglycerides (neutral fats), the phospholipids and the sterols which are the principal and most efficient source of stored energy because of high fuel value (9.3 calorie/g). These fat reserves are constantly broken down and re-synthesized. An optimal nutrition must contain a certain amount of fat along with essential fatty acids. Previously carbohydrates were attributed for major source of energy but increasing evidences had established the fact that fat is the chief source of energy for many tissues and perhaps the main source of energy for the body as a whole.

Lipids: Digestion, Absorption and Secretion

Daily intake of lipids is approximately 80g of which more than 90% is normally triacylglycerol (TAG) or triglyceride while remaining consists of cholesterol, its esters, phospholipids and unsterilized (free) fatty acid.

Digestion & Emulsification

The lipids digestion begins in the stomach by lingual lipase (acid-stable) present on the back of the tongue and gastric lipase present in the gastric mucosa. The lipases mainly digest TAG with short or medium chain length (≤ C12) as present in milk. The emulsification of lipids crop up in the duodenum where the surface area of the hydrophobic lipid molecules increases for effective digestion by enzymes via two modes i.e. through the mechanical mixing and detergent property of bile salts resulting from peristalsis. In liver, bile salts are synthesized and stored in the gall bladder are actually imitative of cholesterol. Emulsification actually stabilizes the smaller individua l particles and prevents them from coalescing.

Dilapidation of Lipids

The dietary lipids are degraded by enzymes of pancreas and the secretions of these pancreatic enzymes are hormonally regulated.

TAG

TAG are large enough to be degraded by mucosal cells of intestinal villi, thus they are first converted to monoacylglycerol and free fatty acid by esterase and pancreatic lipase.

Cholesteryl Ester

Overall dietary cholesterol is present mostly in free non-esterified form while only 10-15% occurs in esterified form. Cholesteryl ester is degraded by pancreatic cholesteryl ester hydrolase (or known as cholesterol esterase) which produces free fatty acid and cholesterol. In presence of bile salts, the enzyme activity gets increased.

Phospholipids

Phospholipids are acted upon by activated pancreatic phospholipase A2 and ultimately forming fatty acid and lysophospholipid. The lysophospholipid is acted upon by lysophospholipase leaving a glyceryl phosphoryl base that may be excreted in the feces or it can be further degraded or absorbed by the body.

Hormonal Control

Cholecystokinin (CCK) which is a small peptide hormone secreted by mucosal cells of lower duodenum and jejunum. It acts on gallbladder, exocrine cells of pancreas and small intestine. Another hormone, secretin produced by intestinal cells helps in balancing pH for optimum activity.

Absorption of lipids is done mainly by enterocytes (mucosal cells of intestine). Before absorption, these lipids are ultimately breakdown in jejunum into 2-monoacylglycerol, cholesterol and free fatty acids which are the key products. After that micelles are formed in the intestinal lumen and then these lipid droplets are absorbed in the brush border membrane of the enterocytes. In enterocytes, re-synthesis of TAG and cholesteryl esters occurs.

Secretion

The newly re-synthesized cholesteryl esters and TAGs are incredibly hydrophobic in nature therefore it is obligatory to package it as lipid droplet surrounded by thin layer of phospholipid, Apolipoprotein-B and unesterified cholesterol. This helps in stabilization and increase solubility.

Utilization of Lipids in Different Compartments of Animals

TG: triacylglycero l, M G: Monoacylglycerol, FFA: Free fatty acid, PI: Phospholipids, KB: Ketone bodies, VLDL: Very lo wdensity lipoproteins, HDL: High density lipoproteins

These particles known as chylomicrons are released from enterocytes into the lacteals (lymphatic sytem present in small intestine villi).

Use of Released Chylomicrons by Tissues

In adipose tissue and skeletal muscle mainly, but also in kidney, heart, liver and lung; these chylomicrons are broken down to TAG which are further degraded into free fatty acid and glycerol by lipoprotein lipase. The 9 paucity of lipoprotein lipase or its coenzyme apolipoprotein-C II also known as ‘Familial lipoprotein lipase’ deficiency or ‘Type I hyper-lipoproteinemia’ is an exceptional autosomal recessive disorder

Chylomicrons: Assembly and Secretion by Intestinal Mucosal Cells

Destiny of Free Fatty Acid

The free fatty acids may enter adipocytes or muscle cells or may be transported in blood in conjugation with serum albumin until taken up by peripheral tissues. Adipocytes can again produce TAG from free fatty acids which are stored until needed. In adipocytes, hormone-sensitive lipases hydrolyze TAGs and release the fatty acids (free fatty acids) into the blood, wherever they bind with serum albumin.

Albumin (Mr 66,000) which is more or less half of the total serum protein binds non-covalently to as much as 10 fatty acids per monomer of protein. The inexplicable fatty acids have been passed to tissues such as heart, renal cortex and skeletal muscle. To serve as a fuel in these target tissues, fatty acids secede from albumin and are moved by the transporter of plasma membrane into the cells. Numerous proteins other than serum albumin also act as transporters to carry the absorbed TAGs from intestine to different organs and tissues such as liver, heart, muscle and adipose tissues via blood. These proteins wrap around the lipid molecule to facilitate their movement across the membranes in cells.

Entrance of Fatty Acid into the Cell through the Plasma Membrane

The fatty acid binding proteins (FABPs) present in the cytosol of diverse animal tissues have low molecular weight (14-15 kDa). In the cytosolic compartment, it functions as carrier of fatty acids. FABPs may also be implicated in the intracellular storage, the delivery of fatty acids and/or cellular uptake of fatty acids to the sites of their consumption. In fatty acid metabolism, the significance of FABPs is sustained by the reduction in exploitation and uptake of long chain fatty acids in knockout mice deficient in heart FABE. These animals develop cardiac hypertrophy and exhibit exercise intolerance during aging. Nevertheless, the molecular mechanism of FABP function remains to be explicated.

Destiny of Glycerol

Used exclusively by liver to produce glycerol-3-phosphate entering glycolysis or gluconeogenesis. About 95% of the biologically accessible energy of TAGs resides in their long chain fatty acids and merely 5% is supplied by the glycerol moiety. The released glycerol obtained by the action of lipase is phosphorylated by glycerol kinase and the ensuing glycerol 3-phosphate (G3P) is oxidized to dihydroxyacetone phosphate (DHAP). The triose phosphate isomerase, which is a glycolytic enzyme converts G3P to glyceraldehyde 3-phosphate which is auxiliary oxidized through the glycolysis pathway.

Destiny of Remaining Portion of Chylomicron

After maximum TAGs had been removed, the remaining portion (containing cholesteryl esters, phospholipids, fat soluble vitamins, apolipoprotein and few TAG) present on liver cells binds to the receptors and are endocytosized where they are degraded. If this endocytosis is decreased then they accumulate in the plasma and the condition is clinically known as ‘Type III hyper-lipoproteinemia’ or ‘Familial betalipoproteinemia’.

Summary

In this lecture we learnt about:

Dietary lipids are digested foremost in the stomach and intestines.
Emulsification is an essential step required for efficient metabolism of dietary lipids. In milk, TAG contain short to medium length fatty acid degraded by lingual and gastric lipase but other dietary lipids needs pancreatic enzymes. The primary product from degradation results into free fatty acids, unesterified cholesterol and 2-monoacylglycerol. The major compounds along with the fat soluble vitamins together form the mixed micelles that assist in the absorption of dietary lipids by enterocytes (intestinal mucosal cells).
Cells re-synthesize CE, PL and TAG also synthesizes apolipoprotein B48, each of which are then assembled into chylomicrons with the fat-soluble vitamins which are released in the blood via lymphatic system. Medium and short chain fatty acids infiltrate into the blood directly. Thus, dietary lipids are elated to the peripheral tissues. The problems associated with the fat absorption causes steatorrhoea.

you can view video on Oxidation of Lipids I

Weblinks

Books

Lehninger Principles of Biochemistry by David L. Nelson, ‎Albert L. Lehninger, ‎Michael M. Cox. 2008. https://books.google.co.in/books?isbn=071677108X
Fat Digestion and Absorption by Armand B. Christophe, ‎Stephanie DeVriese. 2000. https://books.google.co.in/books?isbn=189399712X
The Digestion and Assimilation of Fat in the Human Body: … by H. Critchett Bartlett – 1877. https://books.google.co.in/books?id=0cYFgIU7EIcC
Lipid Biochemistry: An Introduction by Michael I. Gurr, ‎Professor John L. Harwood, ‎Keith N. Frayn – 2008. Page 170. https://books.google.co.in/books?isbn=1405172703
Lingual and Gastric Lipases: Their Role in Fat Digestion by Margit Hamosh. 1990 . https://books.google.co.in/books?id=fvZqAAAAMAAJ