Enzymes, Transporters, Proteins: Lipids and Proteins

Lingual lipase — function

Begins TAG hydrolysis; contributes to early digestion, especially of short- and medium-chain fatty acids.

Lingual lipase — location

Secreted by lingual glands; acts in the mouth and remains active in the stomach.

Gastric lipase — function

Hydrolyzes TAG to DAG and free fatty acids; contributes to early fat digestion and works at acidic pH.

Gastric lipase — location

Stomach; secreted by gastric chief cells.

Pancreatic lipase — function

Major dietary TAG-digesting enzyme; hydrolyzes fatty acids at positions 1 and 3, yielding 2-MAG and free fatty acids.

Pancreatic lipase — location

Small-intestinal lumen, especially duodenum; works at the lipid-water interface with colipase.

CD36, FATP4, FABPpc — function

Facilitate fatty-acid uptake at the enterocyte surface and intracellular fatty-acid handling/transport.

CD36, FATP4, FABPpc — location

Small-intestinal enterocytes; associated with brush-border membrane and intracellular handling, depending on protein.

Acyl-CoA synthetase — function

Activates free fatty acids to fatty acyl-CoA for re-esterification, lipid synthesis, or oxidation.

Acyl-CoA synthetase — location

Cellular membranes/intracellular surfaces; varies by tissue and isoform.

NPC1L1 — function

Transports cholesterol into enterocytes from the intestinal lumen.

NPC1L1 — location

Apical/brush-border membrane of small-intestinal enterocytes.

ABCG5/8 — function

Exports sterols, including cholesterol, from enterocytes back into the intestinal lumen, limiting absorption.

ABCG5/8 — location

Apical/brush-border membrane of enterocytes.

ACAT — function

Esterifies free cholesterol to cholesteryl esters for incorporation into chylomicrons.

ACAT — location

Inside enterocytes, mainly endoplasmic reticulum.

Chylomicrons — function

Carry dietary TAG and cholesterol from intestine to tissues; after LPL removes TAG, remnants deliver remaining cholesterol to liver.

Chylomicrons — location

Assembled in enterocytes; travel through lymph then blood; remnants are taken up by liver.

ApoB48 — function

Essential structural protein for chylomicron assembly; indicates intestinal origin.

ApoB48 — location

Made in enterocytes; found on chylomicrons and chylomicron remnants.

MTP — function

Loads/transfers TAG and other lipids onto ApoB during lipoprotein assembly.

MTP — location

Endoplasmic reticulum of enterocytes and hepatocytes; needed for chylomicron and VLDL assembly.

ApoE — function

Helps liver recognize and take up chylomicron remnants and some IDL/remnant particles.

ApoE — location

On chylomicron remnants and VLDL/IDL; acts as a recognition signal for hepatic uptake.

ApoB-100 — function

Structural protein of VLDL, IDL, and LDL; serves as LDL-receptor ligand on LDL.

ApoB-100 — location

Made in liver; found on VLDL, IDL, and LDL in blood.

VLDL — function

Exports endogenous TAG and cholesterol from liver to peripheral tissues; loses TAG through LPL and becomes IDL.

VLDL — location

Assembled in liver; circulates in blood.

LDL — function

Cholesterol-rich particle delivering cholesterol to tissues and cleared mainly by LDL-receptor-mediated uptake.

LDL — location

Circulating blood; taken up by peripheral tissues and liver.

HDL — function

Collects cholesterol from peripheral tissues for reverse cholesterol transport toward liver; donates ApoC-II and ApoE to other particles.

HDL — location

Produced by liver and intestine; circulates in blood and interacts with tissues and liver.

ApoA / ApoA-I — function

Major HDL apoprotein; supports HDL function and activates LCAT for cholesterol esterification.

ApoA / ApoA-I — location

On HDL in blood.

LPL — function

Hydrolyzes TAG in chylomicrons and VLDL, releasing fatty acids for tissue uptake; activated by ApoC-II.

LPL — location

On capillary endothelial surfaces, especially adipose tissue, skeletal muscle, and heart.

ApoC-II — function

Activates LPL, enabling TAG hydrolysis.

ApoC-II — location

Exchanged from HDL onto chylomicrons and VLDL in blood.

ApoC-III — function

Inhibits LPL-mediated TAG clearance; opposes ApoC-II.

ApoC-III — location

On TAG-rich lipoproteins such as chylomicrons and VLDL.

LDL receptor (LDL-R) — function

Binds ApoB-100 on LDL (and ApoE on certain remnants) to mediate uptake and clear LDL from blood; normally recycles.

LDL receptor (LDL-R) — location

Cell surface, especially liver hepatocytes; also other cells.

PCSK9 — function

Promotes LDL-receptor degradation/reduces recycling, leaving fewer receptors to clear LDL; inhibition preserves receptors.

PCSK9 — location

Secreted mainly by liver; acts on LDL receptors during cell-surface trafficking.

ABCA1 — function

Exports cellular cholesterol and phospholipids to lipid-poor ApoA-I, initiating nascent HDL formation.

ABCA1 — location

Cell membrane of peripheral cells, including macrophages; also liver and intestine.

SR-B1 — function

Participates in HDL cholesterol exchange; in liver, supports selective uptake of HDL cholesteryl esters.

SR-B1 — location

Cell surface, especially liver and steroidogenic tissues; also peripheral cells.

LCAT — function

Esterifies free cholesterol on HDL; cholesteryl esters move into HDL core and help HDL mature.

LCAT — location

Circulating plasma; associates with HDL.

ABCG1 — function

Promotes cholesterol efflux from cells to mature HDL.

ABCG1 — location

Cell membrane of peripheral cells/macrophages.

CETP — function

Transfers cholesteryl esters from HDL to other lipoproteins, usually in exchange for TAG; does not export cholesterol from cells to HDL.

CETP — location

Plasma; acts between circulating lipoprotein particles.

GPAT — function

Starts glycerol-3-phosphate pathway of TAG synthesis by adding a fatty acyl group to glycerol-3-phosphate.

GPAT — location

Primarily endoplasmic reticulum and mitochondrial-associated membranes, depending on isoform.

MGAT — function

Adds a fatty acyl group to MAG to form DAG.

MGAT — location

Endoplasmic reticulum; important in enterocytes.

DGAT — function

Adds the final fatty acyl group to DAG to form TAG.

DGAT — location

Endoplasmic reticulum.

ATGL — function

Initiates stored TAG breakdown: TAG → DAG + fatty acid.

ATGL — location

Adipocyte lipid droplets; regulated by lipid-droplet proteins.

HSL — function

Hydrolyzes stored DAG (and some TAG/cholesteryl esters), releasing fatty acids during stimulated lipolysis.

HSL — location

Adipocytes; recruited/activated at lipid droplets during lipolysis.

MGL — function

Completes lipolysis by hydrolyzing MAG to glycerol and a fatty acid.

MGL — location

Adipocytes; associated with lipid droplets/cytosolic interface.

Perilipin — function

Coats lipid droplets and regulates lipase access to stored TAG; phosphorylation during stimulation facilitates lipolysis.

Perilipin — location

Surface of adipocyte lipid droplets.

CPT1 — function

Transfers a long-chain fatty acyl group from CoA to carnitine for mitochondrial entry; inhibited by malonyl-CoA.

CPT1 — location

Outer mitochondrial membrane.

CPT2 — function

Transfers fatty acyl group from carnitine back to CoA in mitochondrial matrix so beta-oxidation can proceed.

CPT2 — location

Inner mitochondrial membrane, matrix-facing side.

Acetyl-CoA carboxylase (ACC) — function

Converts acetyl-CoA to malonyl-CoA; key regulated step in de novo fatty-acid synthesis.

Acetyl-CoA carboxylase (ACC) — location

Cytosol.

Malonyl-CoA — function

Provides two-carbon units for fatty-acid synthesis and inhibits CPT1, reducing mitochondrial entry of long-chain fatty acids for oxidation.

Malonyl-CoA — location

Produced in cytosol; acts as a metabolic signal regulating CPT1.

Pepsin/Pepsinogen — function

Pepsinogen is the inactive precursor; stomach acid converts it to pepsin, which digests dietary proteins into smaller peptides.

Pepsin/Pepsinogen — location

Pepsinogen is secreted by gastric chief cells; activation and pepsin activity occur in the stomach lumen.

Trypsin/Trypsinogen — function

Trypsinogen is an inactive pancreatic precursor; enteropeptidase activates it to trypsin, which digests proteins and activates other pancreatic zymogens.

Trypsin/Trypsinogen — location

Trypsinogen is secreted by the pancreas; activation and trypsin activity occur in the small-intestinal lumen.

PepT1 — function

Uses the H+ gradient to transport dipeptides and tripeptides into intestinal epithelial cells.

PepT1 — location

Apical brush-border membrane of small-intestinal enterocytes.

Alanine Amino Transferase (ALT) — function

Reversibly transfers an amino group between alanine and α-ketoglutarate, producing pyruvate and glutamate.

Alanine Amino Transferase (ALT) — location

Primarily in the cytosol; abundant in hepatocytes.

Aspartate Amino Transferase (AST) — function

Reversibly transfers an amino group between aspartate and α-ketoglutarate, producing oxaloacetate and glutamate.

Aspartate Amino Transferase (AST) — location

Found in both the cytosol and mitochondria.

Carbamoyl-Phosphate Synthetase I (CPS I) — function

Uses ammonia, bicarbonate, and ATP to form carbamoyl phosphate; catalyzes the first committed step of the urea cycle.

Carbamoyl-Phosphate Synthetase I (CPS I) — location

Mitochondrial matrix of liver cells.

Argininosuccinate Synthase — function

Combines citrulline and aspartate to form argininosuccinate in the urea cycle; aspartate supplies the second nitrogen that enters urea.

Argininosuccinate Synthase — location

Cytosol of liver cells.

Glutamate Dehydrogenase (GDH) — function

Catalyzes the reversible conversion of glutamate to α-ketoglutarate; oxidative deamination releases ammonium.

Glutamate Dehydrogenase (GDH) — location

Mitochondrial matrix.

Glutamine Synthase — function

Uses ATP to combine glutamate and ammonia to form glutamine, helping capture and transport nitrogen.

Glutamine Synthase — location

Cytosol in multiple tissues, including muscle and brain.

Glutaminase — function

Converts glutamine to glutamate and releases ammonium.

Glutaminase — location

Mitochondria; important in liver, kidney, and intestine.

Branched Chain Amino Transferase (BCAT) — function

Transfers an amino group from leucine, isoleucine, or valine to α-ketoglutarate, forming a branched-chain keto acid and glutamate.

Branched Chain Amino Transferase (BCAT) — location

Mainly extrahepatic tissues, especially muscle; cytosolic and mitochondrial forms occur.

BCKA Dehydrogenase (BCKD complex) — function

Oxidatively decarboxylates branched-chain keto acids produced from leucine, isoleucine, and valine.

BCKA Dehydrogenase (BCKD complex) — location

Mitochondrial matrix.