LIPID CATABOLISM
(BREAKDOWN, STORAGE AND SUPPLY
PROCESSES)
References: Garrett/Grisham Biochemistry (4th ed), chs. 23 and sections of 24
Berg, Tymoczko & Stryer Biochemistry (6ht ed)., sections of ch 26
Lupton et al Dietary Reference Intakes, National Academies Press, 2005.
LIPIDS ARE A PART OF OUR DIET
THAT CONTRIBUTE A LOT OF
FLAVOR (PIZZA!) ….AND SOME
PROBLEMS WITH STORAGE
ACCUMULATION (FAT & PLAQUE!).
WE CANNOT DO WITHOUTLIPIDS
IN OUR DIETS. THIS LECTURE IS
NOT ABOUT WEIGHT CONTROL –
IT IS A BIOCHEMICAL EXPOSE’ OF
HOW LIPIDS ARE “DIGESTED”.
OUTLINE:
1) INGESTION AND BREAKDOWN OF LIPIDS
2) TRANSPORT OF DIETARY LIPIDS TO CELLS
--WITH THE CHOLESTEROL CONNECTION
3) STORAGE OF LIPIDS AND VARIATIONS
4) MOBILIZATION OF LIPIDS FROM STORAGE
5) CONVERSION TO ENERGY
LIPIDS ARE INGESTED INTO THE BODY IN BASICALLY
TWO FORMS: TRIACYLGLYCEROLS AND CHOLESTERYL
ESTERS. (This is in an approximate ratio of 9:1.)
THE BODY WILL USE THE FATTY ACIDS
FROM THE TRIACYLGLYCEROLS FOR:
1) ENERGY
2) MEMBRANE SYNTHESIS
WHILE THE CHOLESTEROL FROM THE
CHOLESTERYL ESTERS WILL BE USED
FOR:
1) MEMBRANE SYNTHESIS
2) HORMONE FORMATION
INGESTION
THREE AREAS IN THE
GASTROINTESTINAL TRACT
IN WHICH LIPIDS COULD
BE BROKEN DOWN OR
PROCESSED:
B
A: THE STOMACH
B: THE DUODENUM
C: THE INTESTINAL
EPITHELIUM
DUODENAL
LIPIDS
and cholesteryl esters
A
C
THE STOMACH
IS THE 1st ORGAN IN WHICH TRIACYLGLYCEROLS AND
CHOLESTEROL/ ESTERS RESIDE, BUT VERY LITTLE CHANGE
OCCURS HERE DUE TO STOMACH ACIDITY (& ENZYME ABSENCE).
THE DUODENUM
CONTAINS ALKALINE PANCREATIC & GALL BLADDER SECRETIONS
MADE UP OF PANCREATIC LIPASES , ESTERASES & BILE SALTS TO
BREAK DOWN TRIACYLGLCEROLS & CHOLESTERYL ESTERS.
PANCREATIC LIPASES & ESTERASES
NOTE: n-sp LIPASES REMOVE THE FATTY ACID FROM THE
2 POSITION AND AS WELL AS THE FATTY ACIDS FROM
CHOLESTERYL ESTERS.
RELEASED
FATTY ACIDS
INTESTINAL EPITHELIUM (mucosal cells)
1) SHORT CHAIN FATTY ACIDS (<10 C)
ARE DIRECTLY TAKEN UP INTO THE
INTESTINAL MUCOSAL CELLS
WHILE LONGER CHAIN FATTY ACIDS
+ BILE SALTS (MIXED MICELLES) ARE
CARRIED TO THE EPITHELIAL CELLS
(MUCOSAL CELLS) FOR UPTAKE.
1) LIPID UPTAKE
Intestinal lumen
2) CONDENSATION
2) INSIDE THE EPITHELIAL CELLS
NEW TRIACYLGLYEROLS AND
CHOLESTERYL ESTERS ARE
REFORMED (CONDENSED) BY THE
ACTION OF AN ACYL TRANSFERASE.
3) THE NEW LIPID ESTERS ARE
COMBINED WITH APOLIPOPROTEINS
TO FORM CHYLOMICRONS FOR
TRANSPORT THROUGH THE LYMPH
AND BLOOD VESSELS.
3) “PACKAGING”
TRANSPORT
LIPIDS AS TRIACYLGLYCEROLS,
CHOLESTEROL AND CHOLESTERYL
ESTERS BEGIN TO MOVE THROUGH
THE BODY AS CHYLOMICRONS –
SPHERICAL BODIES THAT ALSO
CONTAIN PHOSPHOLIPIDS AND
APOLIPOPROTEINS BOUND AT
THE SURFACE.
THE PHOSPHOLIPIDS COME FROM
THE MUCOSAL CELL PMs WHILE
THE APOLIPOPROTEINS ARE
FROM THE MUCOSAL CELL INTERIOR. THE
APOLIPOPROTEINS ACT AS MARKERS AND ACTIVATORS FOR THE
RELEASE OF CHYLOMICRON CONTENTS AT SPECIFIC KINDS OF CELLS.
IN THE TRANSPORT OF LIPIDS, CHYLOMICRONS DELIVER LIPIDS TO ADIPOSE TISSUE
AND PERIPHERAL TISSUES (1) WHILE THE REMNANTS GO TO THE LIVER (2).
VERY LOW DENSITY
LIPOPROTEINS LEAVE THE
LIVER AND DELIVER LIPIDS
TO ADIPOSE AND PERIPHERAL
TISSUES (3). THE REMNANTS
ARE CONVERTED TO LOW
DENSITY LIPOPROTEINS (LDL)
AND GO TO PERIPHERAL
TISSUES AND THE LIVER (4).
AT PERIPHERAL TISSUES, HIGH
DENSITY LIPOPROTEINS (HDL)
ARE FORMED FROM PRECURSORS AND GO TO THE
LIVER (5).
HDL
precursor
1
3
1
3
4
2
5
THE MOST “SIGNIFICANT” LIPOPROTEINS IN MEDICAL RESEARCH ARE PRESENTLY THE
LOW DENSITY LIPOPROTEINS (CONTAINING SO CALLED “BAD” CHOLESTEROL) AND
HIGH DENSITY LIPOPROTEINS (CONTAINING SO CALLED “GOOD” CHOLESTEROL).
DELIVERY OF LIPIDS TO/ FROM CELLS & BLOOD CHOLESTEROL LEVELS
WHAT ARE THE ROLES OF THE LDL AND HDL LIPOPROTEINS? LDL LIPOPROTEINS CARRY
CHOLESTEROL MOLECULES TO PERIPHERAL TISSUES AND REGULATE NEW CHOLESTEROL
SYNTHESIS AT THESE SITES. HDL LIPOPROTEINS PICK UP CHOLESTEROL RELEASED INTO
BLOOD PLASMA FROM DYING CELLS AND FROM CELL MEMBRANE TURNOVER. HDL IS A
CHOLESTEROL SCAVENGER AND DETERS BUILD-UP OF CHOLESTEROL PLAQUE INSIDE OF
BLOOD VESSELS BY TAKING IT TO THE LIVER.
IT IS IMPORTANT THAT LDL IS ABLE TO
DELIVER CHOLESTEROL TO ITS TARGET
CELLS AND HDL IS ABLE TO PICK UP
DISCARDED CHOLESTEROL. AN INDICATION OF HOW WELL THIS IS WORKING
CAN BE SEEN IN A LAB TEST OF THE
HDL/ LDL RATIO WHICH IDEALLY IS 3.5:1.
THIS FUNCTIONAL ABILITY IS RELATED
TO THE APOLIPOPROTEINS THAT ARE FOUND ON LDL (B100) AND HDL (A). B100 CAUSES
CHOLESTEROL UPTAKE INTO CELLS, BUT AN ABSENCE OF RECEPTORS FOR B1OO LEADS TO
FAMILIAL HYPERCHOLESTEROLEMIA.
DELIVERY MECHANISM OF CHOLESTEROL TO ADIPOCYTES AND MUSCLE CELLS
THE UPTAKE OF CHOLESTEROL INTO ITS TARGET CELLS USES RECEPTOR MEDIATED
ENDOCYTOSIS FOR LDL LIPOPROTEINS. THE PROCESS BEGINS (1) WITH THE BINDING OF
AN LDL BODY IN
A COATED PIT WITH
AN LDL RECEPTOR.
AFTER INVAGINATION
(1)
& REMOVAL OF A
(3)
COAT PROTEIN (2),
THE TRAPPED LDL IS
FUSED WITH A LYSOSOME(LYS). THE LYS
HAS DEGRADATIVE
ENZYMES (**) THAT
DEGRADE ITS apo-B
& CHOLESTEROL
ESTERS INTO AMINO (2)
(4)
ACIDS & FREE CHOLESTEROL (3). CHOLESTEROL MAY THEN
BE STORED OR USED FOR MEMBRANE SYNTHESIS (4). Note: ACAT should be LCAT.
**PROTEASES FOR apo-B AND LCAT(lecithin:cholesterolacyltransferase)for cholesterol esters.
HOW ARE TRIACYLGLYEROLS RELATED TO CHOLESTEROL LEVELS?
WHAT ABOUT THE DELIVERY OF TRIACYLGLYCERIDES TO CELLS?
TRIACYLGLYEROLS ARE TRANSPORTED TO ADIPOCYTES AND
PERIPHERAL TISSUES (e.g. MUSCLES) VIA CHYLOMICRONS
AND VLDLs/LDLs. THE MAJORITY OF TRIACYLGLYCEROLS ARE
CARRIED IN CHYLOMICRONS (NORMAL DIETARY SUPPLY FOR
FAT AND MUSCLE CELLS) AND VLDLS (EXTRA SUPPLY THAT
COMES FROM THE LIVER). CLINICALLY, WHEN SERUM
TRIACYLGLYERIDES (TAGs) ARE ELEVATED, IT USUALLY MEANS
THAT THE LDLs (WITH 2.5 x MORE TAGs THAN HDLs) ARE
INCREASED IN RELATION TO HDLs**. WHEN THIS OCCURS,
CHOLESTEROL IN LDLs INCREASE AS WELL AND THAT
INCREASES THE CHOLESTEROL THAT MIGHT BE DEPOSITED
INSIDE OF CIRCULATORY BLOOD VESSELS.
**
AN ADIPOCYTE
(“cellulite”)
HOW DOES THE COMPOSITION OF FATTY ACIDS IN TRIACYLGLYCEROLS
AFFECT LIPOPROTEIN COMPOSITION?
-- SATURATED vs. UNSATURATED FATTY ACIDS?
-- TRANS vs. CIS FATTY ACIDS?
THIS IS A QUESTION THAT HAS PERPLEXED NUTRITIONAL RESEARCHERS FOR MANY
YEARS. ALL THAT IS PRESENTLY KNOWN SUGGESTS THAT:
1) SATURATED FATTY ACIDS INCREASE LDL LEVELS ONLY.
2) TRANS FATTY ACIDS INCREASE LDL LEVELS AND LOWER HDL LEVELS
THE CAUSE IS UNKNOWN, BUT SOME EVIDENCE INDICATES THAT THIS IS DUE TO
HORMONAL EFFECTS ON THE APOLIPOPROTEIN LEVELS THAT PRODUCE EACH
LIPOPROTEIN CARRIER. THAT IS, THE AMOUNTS OF apoA-1 AND apoB-100 ARE
AFFECTED.
THERE IS NO DOUBT THAT INCREASED SATURATED AND TRANS-FATTY ACIDS IN THE
DIET INCREASE THE LDL TO HDL RATIOS AND, ACCORDINGLY, THE AMOUNT OF
CHOLESTEROL THAT CAN BE “DUMPED” INTO BLOOD VESSEL INTERIORS.
WITH ALL OF THAT WE NEED
SOME COMIC RELIEF!
MARY HAD A LITTLE LAMB (OLD VERSION)
“MARY HAD A LITTLE LAMB. ITS FLEECE
WAS WHITE AS SNOW AND EVERYWHERE
THAT MARY WENT, THE LAMB WAS SURE
TO GO.”
THE NUTRITIONAL VERSION OF THAT IS --
MARY HAD
A LITTLE LAMB:
“AND THAT EVENING,
WITH HER BLINDS PULLED
DOWN, MARY HAD 3
HELPINGS OF CORN, A
BAKED POTATO, EXTRA
BREAD, AND A LITTLE
LAMB”
-- WITH APOLOGIES TO
THE LAMB
NEXT: DELIVERY OF FATTY ACIDS TO ADIPOCYTES AND MUSCLE CELLS
WHEN A LIPOPROTEIN CARRIER REACHES ITS TARGET AREA, TAGs ARE RELEASED BY
THE COMBINED ACTION OF THE APOLIPOPROTEIN/RECEPTOR (HOLDS THE CARRIER
NEXT TO THE BLOOD VESSEL ENDOTHELIAL CELL) AND A CELL MEMBRANE BOUND LIPASE
(ENZYME THAT LYSES FFAs AND MONOGLYCERIDES) FOR TRANSPORT INTO THE TARGET
CELL.
THIS WORKS WHEN THE LIPOPROTEIN CARRIER PARKS NEXT TO A BLOOD VESSEL WALL
CELL THAT ENZYMATICALLY RELEASES FFAs AND MONOGLYCERIDES TO BE TAKEN UP BY
TISSUE CELLS ON THE OTHER SIDE OF THE BLOOD VESSEL:
DELIVERY OF FFAs/MONOGLYCERIDES
IS SHOWN FOR CHYLOMICRONS, BUT THE
MECHANISM IS SIMILAR FOR VLDLs AS
WELL.
NOTE THE PRESENCE OF CD36 THAT IS
ASSOCIATED WITH THE RELEASED FFAs.
CD36 IS A PROTEIN THAT BINDS TO THE FATTY
ACID AND TRANSPORTS IT THROUGH THE
ENDOTHELIAL CELL TO THE ASSOCIATED
TARGET CELL.
THE USES OF FATTY ACIDS –
A REVIEW AND AN INTRODUCTION TO b-OXIDATION
EARLIER, IT WAS SAID THAT FATTY ACIDS MAY BE USED TO STORE ENERGY AS WELL
AS TO PRODUCE ENERGY. THERE ARE ALSO MINOR ROLES, FOR EXAMPLE, IN THE
STORAGE FORM - FATTY ACIDS ARE GOOD INSULATORS AND THEY CAN ALSO FORM
INTO HORMONE-LIKE COMPOUNDS.
AS YOU HAVE SEEN, FATTY ACIDS HAVE TO BE CHEMICALLY MINIPULATED TO BE
TRANSPORTED THROUGH THE BODY DUE TO THEIR SOLUBILITY “PROBLEM” IN
AQUEOUS MEDIA SUCH AS BLOOD PLASMA. THIS IS ALSO TRUE INSIDE THE CELL
WHEN IT BECOMES NECESSARY TO USE FATTY ACIDS FOR ENERGY.
IN FACT, THERE ARE MANY CELL TYPES THAT MAKE USE OF
FATTY ACIDS AS AN ENERGY SOURCE WHEN THE BODY IS
STARVED FOR GLYCOGEN /GLUCOSE. NOTE THAT HEART TISSUE
AND MUSCLES NORMALLLY PREFER FATTY ACIDS AS A FUEL
SOURCE. BRAIN TISSUE CAN ONLY USE FATTY ACIDS AFTER
THEY HAVE BEEN BROKEN DOWN TO KETONE BODIES.
ACETOACETATE AND b-HYDROXYBUTYRATE ARE CONVERTED
TO ACETYL-CoA FOR USE IN THE KREB’S CYCLE. THEY ALSO
CONTRIBUTE TO BODY ACIDITY, A PROBLEM IN DIABETES.
A NUTRITIONAL REVIEW OF
FATTY ACID VS. CARBOHYDRATE ENERGY IN METABOLISM
1) TRIACYLGLYCEROLS (TAGs) ARE A MAJOR FORM OF STORED ENERGY:
(70 kg = 154 lbs.)
1 kJ = 0.239 kcal
(TAGs REPRESENT 84% OF ALL THE STORED BODY ENERGY)
660,360 kJ =
~157,827 kcal
2) IN NORMAL METABOLISM (NOT FASTING, STARVING OR DIABETIC):
MUSCLE: FFA ARE PREFERRED, THEN GLUCOSE
HEART: KETONE BODIES ARE PREFERRED, THEN GLUCOSE
BRAIN & RBCs: GLUCOSE IS PREFERRED, THEN KETONE BODIES
KIDNEYS: KETONE BODIES ARE PREFERRED, THEN GLUCOSE
3) FFA  ACETYL CoA  KETONE BODIES  ACETYL CoA  TCA CYCLE
KETONE BODIES ARE A SOLUBLE FORM OF FFA BREAKDOWN THAT
CAN BE TRANSPORTED IN THE BLOOD. SOME ARE ALWAYS PRESENT.
THEREFORE:
1. TAGs (AS FATTY ACIDS) ARE AN IMPORTANT SOURCE OF SUSTAINED
ENERGY IN PERIPHERAL MUSCLE, HEART AND KIDNEYS – THE LATTER
AS KETONE BODIES.
2. UNDER STARVATION CONDITIONS, FATTY ACIDS BECOME VERY IMPORTANT
AS A MAJOR SOURCE OF ENERGY EVEN FOR BRAIN TISSUE.
3. TAGs ARE CONSUMED IN HIGHER THAN REQUIRED AMOUNTS IN THE
DIETS OF MANY OF THE “DEVELOPED” NATIONS…. WITH THE RESULT THAT
CHOLESTEROL MAY BE DUMPED INTO BLOOD VESSELS TO FORM PLAQUE
DUE TO THEIR DELIVERY WITH LDLs CONTAINING TAGs.
THE MOBILIZATION OF STORED LIPIDS
WHEN THE BODY “SENSES” THAT TAGs ARE REQUIRED FROM ADIPOCYTES OR OTHER
CELLS, IT CONVERTS THE TAGs TO A TRANSPORT FORM AND MOVES THEM TO A
LOCATION WHERE THEY CAN BE USED – USUALLY FOR ENERGY.
HOW DOES THE BODY “SENSE” SUCH A NEED?
HOW DOES THE BIOCHEMICAL CONVERSION TAKE PLACE?
WHAT IS INVOLVED IN TRANSPORT?
“SENSATION” OR SIGNALLING OF LIPID NEED & TAG BREAKDOWN
1) MOBILIZATION IS SIGNALLED BY
HORMONE BINDING TO A RECEPTOR
PROTEIN.
2) THIS TRIGGERS A “CASCADE” MECHANISM OF ENZYME ACTIVATIONS.
3) THE LAST ENZYME ACTIVATED IS A
TRIACYLGLYCEROL LIPASE.
4) THE REPETITIVE LIPASE CATALYSIS
CAUSES THE SEQUENTIAL RELEASE
OF FATTY ACIDS FROM TAGs IN THE
ADIPOCYTE.
5) FREE FATTY ACIDS LEAVE THE CELL
1)
5)
2)
2)
3)
(TAG)
4)
NOTE: INACTIVE COMPOUNDS OR ENZYMES ARE IN
RED WHILE ACTIVE COMPOUNDS OR ENZYMES ARE
IN GREEN.
HORMONES INVOLVED IN SIGNALLING LIPID MOBILIZATION:
ALTHOUGH HORMONES AS A CLASS OF BIOCHEMICALS HAVE NOT YET BEEN
ADDRESSED IN THESE LECTURES, SUFFICE IT TO SAY THAT THEY ACT AS
SWITCHES TO TURN ON/ OFF AN INTRACELLULAR PROCESS. THE
EXTRACELLULAR HORMONES INVOLVED IN LIPID MOBILIZATION ARE:
ADRENOCORTICOTROPIC HORMONE (ACTH)
EPINEPHRINE
GLUCAGON
THEY BIND TO A 7-HELIX RECEPTOR PROTEIN IN ORDER TO ACTIVATE THE
CASCADE MECHANISM. CASCADE MECHANISMS WILL BE CONSIDERED LATER
UNDER HORMONES.
WHAT HAPPENS TO THE “RELEASED” FATTY ACIDS OUTSIDE THE CELLS?
ONE MIGHT PREDICT THAT THE
RELEASED FATTY ACIDS ARE TAKEN
UP AGAIN INTO LIPOPROTEIN BODIES
(SUCH AS LDLs) FOR TRANSPORT, BUT
THAT IS NOT THE CASE. THESE FFAs
BECOME BOUND TO THE PROTEIN:
ALBUMIN FOR TRANSPORT.
SHOWN AT THE RIGHT IS AN ALBUMIN
MOLECULE (MW ~65,000) TO WHICH
ARE BOUND 6 PALMITIC ACID (16:0)
MOLECULES (SEEN IN GREY).
THEN, PRIOR TO “HARVESTING” THE
FATTY ACIDS FOR ENERGY, THE FFAs
ARE ACTIVATED BY BEING BOUND TO
CoA (CO-ENZYME A). THE THIOL ESTER THAT RESULTS IS A CARRIER FORM (A SOLUBLE FORM)
FOR TRANSPORT AND THE ENZYMATIC REACTIONS THAT ARE NEEDED FOR THE FATTY ACID
BREAKDOWN.
GETTING TO b-OXIDATION -- BUT
NOT QUITE! FATTY ACIDS OVER 10 CARBONS LONG ALSO HAVE TO BE TRANSPORTED
INTO THE MITOCHONDRIAL MATRIX USING CARNITINE AND SOME “HELPER”
MOLECULES BECAUSE OF THE SOLUBILITY PROBLEM.
(AKA “TRANSLOCASE”)
CARNITINE (CH3)3-N+-CH2-CH0H-CH2-COO- BINDS TO THE ACTIVATED FATTY ACID
AS AN ESTER AND IS CARRIED ACROSS THE OUTER AND INNER MITOCONDRIAL
MEMBRANES USING TWO ACYLTRANSFERASES AND A TRANSPORTER PROTEIN.
A DEFICIENCY OF CARNITINE CAN LEAD TO MUSCLE WEAKNESS. NOTE THEN THAT
CoA IS USED TWICE AS A CARRIER OUTSIDE OF THE MEMBRANES.
b-OXIDATION
(MAKING ATP FROM FATTY ACIDS)
KREB’S CYCLE
b-OXIDATION IS A PROCESS OF
REMOVING 2-CARBON UNITS FROM
FATTY ACIDS TO OBTAIN ENERGY via
THE KREB’S CYCLE. THE FATTY ACIDS
GAIN ENTRY INTO THE MITOCHONDRAL
MATRIX BY MEANS OF A CARNITINE
CARRIER AFTER “ACTIVATION” WITH
CoA. THE FIGURE AT RIGHT
SHOWS THE SERIES OF REACTIONS
INVOLVING BOTH THE a- AND bCARBONS OF THE FATTY ACIDS.
STARTING AT 1, A DOUBLE BOND IS
FORMED BETWEEN THE TWO
CARBONS. AT 2, H2O IS INSERTED
BETWEEN THESE CARBONS. AT 3,
THE REMOVAL OF TWO ELECTRONS/2
Hs FORMS A KETO GROUP ON THE
b-CARBON (PREPARING FOR SPLITTING
THE TWO CARBONS). AT 4, CLEAVAGE OF THE a- AND b- CARBONS FORMS ACETYL CoA
(2 CARBON UNIT) AND FATTY ACYL CoA (-2 CARBONS). THE CYCLE CAN THEN BE REPEATED
AT
.
b- AND OTHER OXIDATION NOTES:
1. THE OXIDATION OF ONE PALMITIC ACID MOLECULE (16:0) YIELDS 106 MOLECULES
OF ATP vs. GLUCOSE WHICH YIELDS 36-38 ATP MOLECULES.
2. THE CONTRIBUTIONS OF TWO ADDITIONAL ENZYMES ARE NECESSARY TO
CONVERT UNSATURATED FATTY ACIDS INTO 2-CARBON UNITS BY b-OXIDATION.
3. BRANCHED CHAIN FATTY ACIDS ARE DEGRADED BY a-OXIDATION. IN REFSUM’S
DISEASE, A METABOLIC DISORDER, THERE IS A DEFECT IN a-OXIDATION. REFSUM’S
DISEASE CAUSES NEUROLOGICAL DISORDERS AND AFFECTS NIGHT VISION. A
SOURCE OF BRANCHED CHAIN FATTY ACIDS COMES FROM CATTLE THAT CONSUME
PLANT CHLOROPHYLL – A SOURCE OF THE BRANCHED CHAIN FATTY ACID:
PHYTANNC ACID.
BRANCHES
RESEARCH NOTE: BROWN VS. WHITE (YELLOW) FAT
THE NEWS MEDIA HAS MADE SOME NOISE ABOUT THE POSSIBILITY ABOUT
“BURNING OFF” EXCESS STORED FAT BY USING A MINOR COMPONENT IN THE
BODY KNOWN AS BROWN FAT. BROWN FAT IS A TISSUE THAT HAS CELLS
HIGH IN MITOCONDRIAL CONTENT. IT HAS BEEN PROPOSED THAT FAT THAT IS
TRANSPORTED TO THIS TISSUE CAN BE OXIDIZED (ESSENTIALLY DESTROYED)
BY THIS TISSUE.
AT PRESENT THERE IS NO PRACTICAL WAY FOR THIS TO BE REALIZED SINCE:
1) THE AMOUNT OF BROWN FAT IS TOO LOW
2) NO ONE KNOWS HOW TO INDUCE THE TRANSPORT OF THE LIPID CONTENT
OF WHITE FAT INTO BROWN FAT TISSUES.
SUMMARY OF LIPID CATABOLISM AND NOTEWORTHY POINTS:
●LIPID TRANSPORT IS COMPLICATED BY THE NON-POLAR
NATURE OF LIPIDS AND THE NEED TO FORM SPECIAL
TRANSPORT FORMS SUCH AS CHYLOMICRA, LIPOPROTEINS &
THE USE OF ALBUMIN TRANSPORTERS. KNOW THIS.
●THE PRINIPAL LIPIDS TAKEN INTO THE GI TRACT ARE FATTY ACIDS
AND CHOLESTEROL (AS TRIACYLGEROLS AND CHOLESTERYL
ESTERS (~9:1). THIS TOO.
●THE PRIMARY USES OF INGESTED LIPIDS ARE: ENERGY,
MEMBRANE SYNTHESIS AND HORMONE FORMATION. AND THIS.
●THE DUODENUM EMUSIFIES AND HYDROLYZES LIPIDS WHILE THE
SMALL INTESTINE RESYNTHESIZES LIPIDS INTO ESTERS AND
FORMS CHYLOMICRA (CHYLOMICRONS). KNOW DETAILS.
●CHYLOMICRA AND LIPOPROTEINS ARE COMPOSED OF LIPIDS AND
APOLIPOPROTEINS. THESE ARE BODIES THAT TRANSPORT LIPIDS
IN THE LYMPH AND BLOOD VESSELS. KNOW THE DETAILS OF EACH
TYPE IN DELIVERING LIPIDS TO EACH CELL TYPE.
●LDLs AND HDLs ARE INVOLVED IN THE POSSIBLE FORMATION OF BLOOD
VESSEL PLAQUE AND CARRY WITH THEM THE MISNOMERS OF “BAD”
AND “GOOD” CHOLESTEROL . WHY IS THAT? WHAT IS THE REALATIONSHIP
OF AN ABSENCE OF RECEPTORS FOR B100 AND FAMILIAL HYPERCHOLESTEROLEMIA?
●CHOLESTEROL IS TAKEN UP INTO CELLS BY ONE MECHANISM WHILE
TRIACYLGLYCEROLS BY ANOTHER. KNOW THE DIFFERENCE AND THE
DETAILS.
●CLINICALLY AN ELEVATED LDL VS. HDL MIGHT BE A SIGN OF THE
POSSIBILITY OF ARTERIAL CLOGING. WHY IS THAT? WHAT MIGHT AN
INCREASED INTAKE OF SATURATED VS. UNSATURATED FATTY ACIDS
OR TRANS VS. CIS FATTY ACIDS CAUSE?
●b-OXIDATION BREAKS DOWN FATTY ACIDS INTO TWO CARBON UNITS. HOW IS
THIS DONE AND WHY IS IT DONE? DETAILS! WHAT IS THE CHEMICAL MECHANISM?
●SOME CELLS PREFER GLUCOSE, SOME FATTY ACIDS AND SOME KETONE BODIES AS
SOURCES OF ATP. DOES THIS CHANGE YOUR OUTLOOK ON NUTRITION AND,
PERHAPS, YOUR RELATIVE EVALUATION OF GLUCOSE VS. FAT METABOLISM?
WHAT ENERGY SOURCE BECOMES QUITE IMPORTANT UNDER STARVATION
CONDITIONS?
●WHAT IS MEANT BY THE “MOBILIZATION” OF LIPIDS? HERE AN UNDERSTANDING OF
THE ROLE OF HORMONES BECOMES IMPORTANT AS WELL AS THE CARRIER PROTEIN:
ALBUMIN. THIS IS ALSO IMPORTANT.
●WHAT IS REFSUM’S DISEASE AND WHAT OXIDATION PROCESS IS IT RELATED TO?
THIS SUMMARY – YOU MUST REALIZE – IS ALSO A STUDY GUIDE!
☺