Metabolic Syndrome and Lipid Transport Quiz

Lipids Chemistry

• Lipids are a heterogeneous group of compounds related to fatty acids.
• Classification of Lipids: Simple Lipids, Compound Lipids, Derived Lipids.

Simple Lipids

• Esters of fatty acids with alcohols
• Subclassified based on the alcohol:
  • Neutral fats
  • Waxes

Neutral Fats

• Esters of fatty acids with glycerol
• Also called triglycerides or triacylglycerols
• Carry no charge
• Can be fats (solid) or oils (liquid)
  • Fats are solid due to high saturated fatty acid content
  • Oils are liquid due to high unsaturated fatty acid content

Waxes

• Esters of fatty acids with alcohols higher than glycerol in molecular weight
• The alcohol is monohydric (one OH group)
• Examples include beeswax and lanoline

Compound Lipids

• Esters of fatty acids with alcohols and containing other groups
• Subclassified based on the additional groups:
  • Phospholipids
  • Glycolipids
  • Lipoproteins

Phospholipids

• Contain fatty acids, alcohol, and a phosphate radical (phosphoric acid)
• Also contain nitrogen-containing bases
• The alcohol can be glycerol (glycerophospholipids) or sphingosine (sphingophospholipids)

Glycolipids

• Contain carbohydrate radicals in addition to fatty acids and alcohol

Lipoproteins

• Contain protein radicals in addition to fatty acids and alcohols

Derived Lipids

• Substances obtained by hydrolysis of simple or compound lipids
• Substances associated with lipids in nature and related to them in properties and metabolism
• Examples include steroids like cholesterol, cortisol, and progesterone

Fatty Acids

• Monocarboxylic acids obtained from the hydrolysis of fats
• Can be saturated (no double bonds) or unsaturated (one or more double bonds)
• Typically contain an even number of carbon atoms
• Carbon atoms are numbered from the carboxylic end (carbon 1)
• The methyl carbon at the opposite end is known as the omega (ω) carbon
• Nomenclature of unsaturated fatty acids involves two methods: counting from the functional group (COOH) and counting from the end opposite to the functional group (omega).

Classes of Fatty Acids

• Saturated fatty acids (SFAs): contain no C=C double bonds
• Monounsaturated fatty acids (MUFAs): contain one C=C double bond
• Polyunsaturated fatty acids (PUFAs): contain two or more C=C double bonds

Essential Fatty Acids (EFAs)

• Certain polyunsaturated fatty acids (PUFAs) are essential for humans because the body cannot synthesize them.
• Two major families: omega-3 (ω-3 or n-3) and omega-6 (ω-6 or n-6)
• Distinguished by the position of the first double bond from the methyl end
• Examples include alpha-linolenic acid (ALA, ω-3) and linoleic acid (LA, ω-6).

Branched-chain fatty acids

• Most fatty acids are straight-chain.
• Some milk products contain branched-chain fatty acids like phytanic acid.
• Refsum's disease: impairs the oxidation of branched-chain fatty acids, leading to a buildup of phytanic acid and its derivatives in the plasma.

Digestion of Lipids

• The main dietary lipids are triglycerides.
• Digested by lingual lipase, gastric lipase, pancreatic lipase, and intestinal lipase.
• Emulsification (breakdown of large globules into smaller ones) by bile salts is crucial for lipase action.
• Cholesterol and cholesteryl esters are digested and absorbed.
• Phospholipids are digested and absorbed as such or by phospholipase enzymes, producing fatty acids, glycerol, phosphate, and nitrogenous bases.

Absorption of Lipids

• Short-chain fatty acids and glycerol are water-soluble and absorbed directly into the portal circulation.
• Long-chain fatty acids, monoglycerides, and cholesterol form micelles with bile salts, enabling absorption.
• Chylomicrons, lipoprotein complexes containing triacylglycerols, phospholipids, and cholesterol, are then transported through lymphatic vessels.

Lipogenesis (Fatty Acid Synthesis)

• Series of reactions to build fatty acids from acetyl-CoA.
• Three mechanisms: cytoplasmic, mitochondrial, and microsomal
• The primary site occurs in the cytoplasm of various tissues (liver, adipose tissue, mammary gland, etc.)
• The main product is palmitate (16 carbons).

Production of Malonyl CoA

• The rate-limiting step in fatty acid synthesis.
• Carboxylation of acetyl CoA via the enzyme acetyl-CoA carboxylase, using biotin as a cofactor.

Fatty Acid Synthase

• A multi-enzyme complex in eukaryotes
• Involved in the sequential addition of two-carbon units (malonyl-CoA) to a growing fatty acid chain.
• Each subunit has multiple enzymatic activities.

Stages of Fatty Acid Synthesis

• Addition of acetyl and malonyl groups to the acyl carrier protein
• Condensation to form acetoacetyl-ACP
• Reduction, dehydration, and reduction steps
• Addition of a second malonyl to the growing chain, repeating the cycle until a 16-carbon palmitate is formed.
• Release of palmitate.

Microsomal Pathway

• Elongation of existing long-chain fatty acids (C10-C16)
• Uses malonyl CoA and NADPH+H+.
• Primarily in nervous system, producing C22 and C24 fatty acids.

Mitochondrial Pathway

• Elongation of short-chain fatty acids (C14 or less).
• Addition of two-carbon units directly from acetyl CoA.

Desaturation of Fatty Acids

• Located in the smooth endoplasmic reticulum.
• Enzymes that introduce double bonds at specific positions.

Synthesis of Triacylglycerol

• A glycerol backbone esterified with three fatty acids.
• Formation of acyl-CoA from fatty acids and glycerol-3-phosphate.
• Condensation steps to produce triacylglycerol.

Lipid Breakdown (Lipolysis)

• Hydrolysis of triacylglycerols into glycerol and fatty acids by various lipase enzymes.
• Glycerol is converted to pyruvate.
• Fatty acids are transported to mitochondria for oxidation.

Activation of Fatty Acids

• Conversion of fatty acids to fatty acyl CoAs by acyl-CoA synthetase, consuming 2 ATP equivalents.

Transport of Fatty Acyl CoA into Mitochondria

• Utilized carnitine shuttle with carnitine acyltransferases to transfer fatty acyl CoAs across the inner mitochondrial membrane.

Beta-Oxidation

• A cyclic process of four steps that shortens the fatty acyl CoA chain by two carbons in each cycle.
• Produces acetyl CoA, FADH2, and NADH to be used in ATP production through oxidative phosphorylation.

Regulation of Ketogenesis

• Hormonal regulation (insulin, glucagon, etc.) influence ketone body production and utilization based on nutritional status and metabolic needs.

Ketoacidosis

• Occurs when rate of ketogenesis surpasses ketolysis.
• Increased blood ketone levels (ketonemia).
• Excess ketones excreted in urine (ketonuria).
• May lead to metabolic acidosis (ketosis).

Cholesterol Metabolism

Role of Cholesterol

• Essential component of cell membranes.
• Precursor of steroid hormones (e.g., estrogens, androgens), bile acids, and vitamin D.

Cholesterol Synthesis

• Occurs primarily in the liver and other tissues in the cytoplasm and endoplasmic reticulum.
• Occurs in two stages: production of isoprene unit [isopentenyl pyrophosphate (IPP)] from acetyl-CoA; and progressive condensation of the isoprene unit to form squalene.
• Rate limiting step: HMG-CoA reductase conversion of HGM-CoA to mevalonate.
• Controlled by feedback inhibition, cholesterol inhibits the enzyme HMG-CoA reductase. Insulin increases the rate of synthesis.

Packaging of Cholesterol

• Cholesterol is esterified with fatty acids for efficient transport and storage.
• Acyl CoA: cholesterol transferase (ACAT) is involved in cellular esterification.
• In HDL: LCAT catalyzes the process.

Lipid Transport

• Lipids are transported in lipoprotein complexes for solubility. These complexes have various protein components and differing lipid compositions.
• Two major pathways: exogenous (dietary lipids) and endogenous (synthesized lipids).
• Lipoproteins: chylomicrons, VLDLs, IDLs, LDLs, and HDLs, carry and deliver lipids and take up cholesterol from different tissues.

Types of Lipoproteins

• Classes of lipoproteins (CMs, VLDLs, IDLs, LDLs, and HDLs) are distinguished by their density (and thus protein content) with high-density lipoproteins (HDLs) containing the most proteins. Each has a differing amount of lipids and proportions of lipids and proteins.
• These lipoproteins have different roles in transporting different lipids.

Fatty Liver (Hepatic Steatosis)

• Accumulation of fat in liver cells.
• Risk factors include obesity, diabetes, high triglycerides, high carbohydrate diets, malnutrition, alcohol abuse, etc.
• Can be simple steatosis (benign) or steatohepatitis (inflammatory) with further stages progressing to fibrosis and cirrhosis.

Acute Fatty Liver of Pregnancy

• A rare complication that typically affects the third trimester.
• Symptoms include nausea, vomiting, fatigue, decreased appetite, and jaundice.