Lipid Metabolism and Related Topics (Video Notes)

A vocabulary-style set of flashcards covering key concepts in lipid digestion/absorption, transport, metabolism, regulation, and related metabolic disorders as presented in the video notes.

Triacylglycerol (TAG)

Main dietary lipid (~99%), a glycerol backbone esterified with three fatty acids.

Dietary lipids components

Includes TAGs, small amounts of phospholipids, cholesterol, cholesteryl esters, carotenoids, and fat-soluble vitamins.

Essential fatty acids

Fatty acids that cannot be synthesized by the body (essential for health).

Energy yield of lipids

Lipids provide about 9 kcal per gram.

Lingual lipase

Acid-stable lipase from the tongue; initiates digestion of TAGs in the stomach, especially short- to medium-chain fatty acids.

Gastric lipase

Pancreas-derived enzyme that digests lipids in the stomach; active at acidic pH.

Emulsification

Process in the small intestine that disperses fat droplets using bile salts/phospholipids to increase surface area for digestion.

Pancreatic lipase

Main digestive lipase; hydrolyzes TAGs; requires colipase for binding to substrates.

Colipase

Pancreatic cofactor that enables pancreatic lipase to act in the presence of bile salts.

2-Monoacylglycerol (2-MAG)

Major product of TAG digestion by pancreatic lipase (about 72%).

1-Monoacylglycerol (1-MAG)

Minor product of TAG digestion (about 6%).

Glycerol + FFAs

Additional products from TAG digestion (about 22% as glycerol and free fatty acids).

Cholesteryl ester hydrolase

Pancreatic cholesterol esterase; digests cholesteryl esters into cholesterol and free fatty acids.

Phospholipase A2

Pancreatic enzyme that degrades phospholipids to lysophospholipids and fatty acids.

Lysophospholipid

Product of phospholipid hydrolysis; important intermediate in lipid digestion.

Micelles

Disc-shaped clusters of amphipathic lipids; solubilize digestion products for absorption at the brush border.

Enterohepatic circulation

Reabsorption of bile salts from the ileum back to the liver.

Reesterification in enterocytes

Absorbed 2-MAG, cholesterol, and lysophospholipids are reassembled into TAGs and cholesteryl esters to form lipoproteins.

Glycerol 3-phosphate

Backbone for TAG and phospholipid synthesis; formed by glycerol kinase in liver/kidney and from DHAP in glycolysis.

Acetyl-CoA carboxylase (ACC)

Committed enzyme of fatty acid synthesis; makes malonyl-CoA; inhibited by phosphorylation.

Malonyl-CoA

Two-carbon donor for fatty acid synthesis; also inhibits CPT I, reducing FA oxidation.

Fatty acid synthase (FAS)

Multienzyme complex that elongates the growing fatty acid chain; main product is palmitate (C16:0).

Palmitic acid

Major de novo product of FA synthesis (C16:0).

Desaturation of fatty acids

Introduction of double bonds (e.g., MUFAs); essential fatty acids cannot be synthesized (linoleic/linolenic acids).

Glycerol-3-phosphate synthesis

Formation of glycerol-3-phosphate; in liver/kidney by glycerol kinase; adipose tissue lacks glycerol kinase.

Depot fat vs tissue fat

Depot fat: stored as TAG in adipose tissue; tissue fat: lipids in cell membranes and organelles.

Adipocytokines

Hormones/cytokines from adipose tissue (e.g., leptin, adiponectin, resistin) influencing metabolism.

Leptin

Adipokine that reduces appetite and increases fatty acid oxidation; signals to hypothalamus.

Adiponectin

Adipokine with weight-reducing effects; enhances insulin sensitivity.

Resistin

Adipokine linked to insulin resistance and obesity.

Lipolysis

Hydrolysis of TAGs in adipose tissue to glycerol and free fatty acids; regulated by hormones.

Hormone-sensitive lipase (HSL)

Key enzyme in lipolysis; activated by hormonal signaling via cAMP/PKA.

cAMP-dependent regulation of lipolysis

Hormones like epinephrine stimulate, insulin inhibits, via PKA and lipase activation.

Beta-oxidation

Major FA oxidation pathway in mitochondria; acetyl-CoA, FADH2, NADH produced.

Acyl-CoA synthetase

Activates fatty acids to form acyl-CoA; requires ATP to AMP and PPi.

Carnitine shuttle

Transports long-chain acyl-CoA into mitochondria via CPT I/II and carnitine.

CPT I & CPT II

Outer-membrane (CPT I) and inner-membrane (CPT II) enzymes that shuttle acyl groups with carnitine.

Malonyl-CoA inhibition of CPT I

Malonyl-CoA blocks CPT I, preventing simultaneous fatty acid synthesis and oxidation.

Beta-oxidation cycle products

Each cycle yields acetyl-CoA, FADH2, and NADH; acetyl-CoA enters TCA.

Propionyl-CoA from odd-chain FAs

Odd-chain fatty acids yield propionyl-CoA that can enter the TCA cycle as succinyl-CoA.

Peroxisomal β-oxidation

Oxidation of very long-chain fatty acids in peroxisomes; produces H2O2.

Zellweger syndrome

Absence of peroxisomes; accumulation of long-chain FAs; severe organ dysfunction.

Alpha-oxidation

Oxidation pathway for branched-chain fatty acids (e.g., phytanic acid) to allow β-oxidation.

Ketogenesis

Synthesis of ketone bodies (acetoacetate, β-hydroxybutyrate, acetone) in liver mitochondria.

Key enzymes of ketogenesis

HMG-CoA synthase and HMG-CoA lyase drive ketone body production.

Ketolysis

Utilization of ketone bodies by extrahepatic tissues; thiophorase (succinyl-CoA:acetoacetate CoA transferase) required.

Regulation of ketogenesis

Driven by increased lipolysis and acetyl-CoA; insulin suppresses, glucagon/epinephrine promote.

Ketosis

Elevated ketone bodies in blood/urine; can cause acidosis in starvation or uncontrolled diabetes.

Arachidonic acid-derived eicosanoids

Prostaglandins, prostacyclins, thromboxanes, leukotrienes; derived from C20 PUFA.

COX-1 & COX-2

Cyclooxygenase isoforms; COX-1 is constitutive; COX-2 induced during inflammation.

Lipoxygenases

Enzymes producing leukotrienes and lipoxins from C20 PUFAs.

Lipid transport lipoproteins

Chylomicrons, VLDL, IDL, LDL, HDL—complexes of lipids and apoproteins.

Apolipoprotein B-48

Chylomicron-specific apoB; essential for chylomicron assembly in intestine.

Apolipoprotein B-100

LDL/VLDL apolipoprotein; ligand for LDL receptor-mediated uptake.

Apolipoprotein C-II

Activator of lipoprotein lipase (LPL) on circulating lipoproteins.

Apolipoprotein E

Liver/hepatic receptor ligand; directs remnant clearance by liver; transfer of CE.

Lipoprotein lipase (LPL)

Hydrolyzes TAG in chylomicrons and VLDL; activated by Apo C-II; transcribed with insulin signaling.

LCAT

Lecithin-cholesterol acyltransferase; esterifies cholesterol on HDL.

CETP

Cholesteryl ester transfer protein; exchanges CE for TAG among lipoproteins.

HDL and reverse cholesterol transport

HDL scavenges cholesterol from tissues and transfers CE to other lipoproteins; protective against atherosclerosis.

LDL receptor

Mediates uptake of LDL via apoB-100; reduction increases cardiovascular risk.

Atherosclerosis risk factors (LDL/HDL ratio)

High LDL and low HDL increase risk; ratio >4 is associated with risk.

Apolipoprotein distribution by lipoprotein type

Chylomicrons and VLDL rich in TAG; LDL rich in cholesterol esters; HDL rich in proteins.

Abetalipoproteinemia

Defect in apoB synthesis; impaired chylomicron/VLDL/LDL formation; fat malabsorption.

Vitamin A (retinol)

Fat-soluble vitamin; derived from carotenoids; important for vision and gene regulation.

Vitamin D (calciferol)

Fat-soluble vitamin activated to calcitriol; regulates calcium absorption and bone mineralization.

Vitamin K

Fat-soluble cofactor for γ-carboxylation of glutamate in clotting factors.

Vitamin E

Fat-soluble antioxidant (tocopherol) protecting lipids from oxidation.

Vitamin C

Water-soluble antioxidant and cofactor for collagen synthesis; regenerates vitamin E.

Vitamin B1 (thiamine)

Coenzyme thiamine pyrophosphate (TPP); essential for PDH and α-ketoglutarate dehydrogenase.

Vitamin B6 (pyridoxine/PLP)

Coenzyme for transaminases and decarboxylases; important in amino acid metabolism.

Folate (B9) and one-carbon metabolism

THF form carries one-carbon units for nucleotide synthesis and methylation; trap with B12 deficiency.

Vitamin B12 (cobalamin)

Cofactor for methionine synthase and methylmalonyl-CoA mutase; requires intrinsic factor for absorption.

Folate trap

In B12 deficiency, methyl-THF accumulates, depleting THF and impairing DNA synthesis.

Necessity of glycine, serine, and one-carbon metabolism

Glycine/serine contribute to one-carbon pool; synthesize nucleotides and methionine.

Urea cycle

Liver pathway converting ammonia to urea for excretion; CPSI is rate-limiting.

Hyperammonemia

Elevated ammonia; can cause cerebral edema and coma; due to liver/urea cycle defects or hepatic failure.

Transamination

Transfer of amino groups between amino acids and α-keto acids; catalyzed by aminotransferases (ALT/AST).

ALT/AST

Aminotransferases used as clinical markers of liver injury; ALT more liver-specific.

Amino acid catabolism overview

Amino acids can be glucogenic, ketogenic, or both; nitrogen disposed as urea.

Branched-chain amino acids (BCAA)

Valine, leucine, isoleucine; transaminated and decarboxylated to produce acetyl-CoA or succinyl-CoA.

Maple Syrup Urine Disease (MSUD)

Defect in branched-chain α-keto acid dehydrogenase; accumulation of BCAAs; sweet-smelling urine.

Phenylketonuria (PKU)

PAH deficiency leading to phenylalanine buildup; musty odor; treat with phenylalanine restriction.

Tryptophan metabolism derivatives

Tryptophan yields niacin and serotonin; defects cause pellagra-like symptoms or depression.

Niacin (B3)

Vitamin used to generate NAD+/NADP+; deficiency causes pellagra.

Hartnup disease

Defective intestinal/renal transport of neutral AAs (incl. tryptophan); Pellagra-like symptoms.

Creatine and creatinine

Creatine phosphate stores energy in muscle; creatinine is its non-enzymatic breakdown product.

Glutathione (GSH)

Tripeptide antioxidant (Gly-Cys-Glu); protects cells from oxidative damage; involved in detoxification.

Glycine metabolism importance

Glycine contributes to heme, purines, creatine, glutathione; forms glycine betaine as a methyl donor.

Amino acid-derived detoxification and conjugation

Amino acids participate in detox and conjugation reactions in liver.

Glycine conjugates and bile salts

Glycine conjugation forms bile salts to aid fat digestion.

Alpha-ketoglutarate (AKG)

TCA intermediate; accepts amino groups in transamination; linked to amino acid metabolism.

Choline and betaine in metabolism

Choline is a precursor to phosphatidylcholine; betaine acts as methyl donor in homocysteine methylation.

One-carbon metabolism overview

Series of reactions transferring one-carbon groups for nucleotide synthesis, methylation reactions, and amino acid metabolism.

What are the components of dietary lipids?

Includes TAGs, small amounts of phospholipids, cholesterol, cholesteryl esters, carotenoids, and fat-soluble vitamins.

What are essential fatty acids?

Fatty acids that cannot be synthesized by the body (essential for health).

How much energy do lipids provide per gram?

Lipids provide about 9 kcal per gram.

What is the function of Lingual lipase?

Acid-stable lipase from the tongue; initiates digestion of TAGs in the stomach, especially short- to medium-chain fatty acids.