TRIGLYCEROL METABOLISMDR ROHINI C SANE

PROFESSOR

DEPARTMENT OF BIOCHEMISTRY

D Y PATIL MEDICAL COLLEGE ,EBENE

TRIGLYCEROL METABOLISM TRIGLYCEROL ---- 15 -20% OF BODY WEIGHT (70 KG BODY EIGHT )10KG ----TG

85- 90% STORED IN ADIPOSE TISSUE

FUNCTIONS

ENERGY PURPOSE ( 9 KCAL /GM)

INSULATING MATERIAL ( MAINTAIN BODY TEMPERATURE)

STORAGE FORM OF ENERGY (FATTY ACIDS IN REDUCED FORMS)

NON POLAR ,HYDROPHOBIC STORED IN PURE FORM WITHOUT ASSOCIATION

WITH WATER (UNHYDROUS STATE)

1 GM GLYCOGEN COMBINES WITH 2GM WATER

PROTEIN/GLYCOGEN -----4 CAL/GM

100000 CAL -------10-11KG STORED FAT--------55 KG GLYCOGEN

SEVERAL WEEKS BODY NEEDS FOR ENERGY –FULFILED BY TG –HIBERNATING

ANIMALS

HUMMING BIRDS -----24000 KM FLYING 40KM /HR FOR 60HRS

TRANSPORT OF LIPIDS

LIPIDS + PROTEINS = LIPOPROTEINS

(INSOLUBLE ) (SOLUBLE) (SOLUBLE)

TRANSPORT --CHYLOMICRONS ,VLDL,LDL, HDL,(ALBUMIN +FREE FATTY ACIDS )

DYNAMIC STATE OF BODY LIPIDS

LIPIDS -------NOT INERT STORAGE COMPOUNDS

DEGRADED & SYNNTHESIZED (CONTINUOUS ) ---DYNAMIC STATE

TG SYNTHESZED IN LIVER IS CARRIED BY VLDL TO ADIPOSE TIISUE FOR STORAGE & LIPOLYSIS FOR ENERGY YEILD

TG SYNTHESIZED IN INTESTINE CARRIED BY CHYLOMICRONS TO PERIPHERAL CELLS FOR THEIR ENRGY NEEDS---( HEART ,LIVER ,MUSCLE CARRIES LIPOLYSIS)

CONCENTRATION OF LIPIDS IN SERUM

LIPID FRACTION RANGE (MG /DL)

TOTAL LIPID 350-800

TRIGLYCEROL 75-150

TOTAL PHOSPHOLIPIDS 125-400

TOTAL CHOLESTEROL 150-250

FREE FATTY ACIDS 5-15

CONTROL OF LIPOLYSIS IN ADIPOSE TISSUE THROUGH C AMP

ATP

EPINEPHRINE I INSULIN, NIACIN ,PGE

NONEPINEPHRINE I

GLUCAGON (ACTIVATION) I (INHIBITION)

THYROXINE I

GLUCOCORTICOIDES I ADENYLATE CYCLASE

TSH ,ACTH ,GH I

C Amp*

INSULIN + I PHOSPHO -DIESTERASE

CAFFEIN -- I

5 Amp

CAFFEIN INCREASES LIPOLYSIS

INSULIN DECEASES LIPOLYSIS

INSULIN INCREASE FATTY ACID SYNTHESIS (LIPOGENIC)

CONTROL OF LIPOLYSIS IN ADIPOSE TISSUE THROUGH C AMP

ATP HORMONE SENSITIVE TG LIPASE

(INACTIVE LIPASE )

C AMP

ACTIVATED

PROTEIN

KINASE

HORMONE SENSITIVE TG LIPASE

ADP (INACTIVE LIPASE )

TRIGLYCEROL ------------------------------------------>DIACYL GLYCEROLFFA + MONOACYL GLYCEROL

FFA + GLYCEROL

Pi

PHOSPHATASE

LIPOLYSIS & LIPOGENESIS REGULATION C Amp promotes lipolysis

C Amp -inhibits fatty acid synthesis (by inhibiting acetyl

Co A carboxylase * )

ACETYL COA--*--MALONYL COA--------FATTY ACID

SYNTHESIS

Lipogenesis and Lipolysis are not simultaneously

operative

FATE OF TRIGLYCEROL TRIGLYCEROL

FATE OF FATTY ACIDS FATE OF GLYCEROL

ADIPOSE TISSUE GLYCEROL 3 PHOSPHATE

BLOOD SYNTHESIS TG &PL DHAP

ALBUMIN

PERIPHERAL CELLS GLYCOLYSIS

(BETA OXIDATION ---90-95% ENERGY NEEDS THROUGH BETA OXIDATION

EXCEPT BRAIN, RBC NO BETA OXIDATION)

Synthesis of Triglycerol

SITE – ADIPOSE TISSUE /LIVER ( LESSER EXENT IN OTHER TISSUE )

FATTY ACIDS (R –CH2-CH2-COO- )

THIOKINASE ATP

PPi –(PYROPHOSPHATASE) 2Pi

ACYLADENLYLATE (R-CH2-CH2-CO-AMP)

COASH

AMP

ACYL COA (R-CH2-CH2-CO—COA)

Synthesis of TriglycerolLIVER

GLYCEROL ----------GLYCEROL 3 P (GLYCERO KINASE)*

* (GLYCERO KINASE)*------ABSENT IN ADIPOSE TISSUE(glycerol cannot be utilized)

LIVER & ADIPOSE TISSUE

GLUCOSE --------GLYCOLYSIS -------DHAP---------REDUCED BY GLYCEROL 3

PHOSPHATE DEHYDROGENASE ----------- GLYCEROL 3 P

SATURATED FAT----- GYCEROL -3P + 3 FATTY ACIDS

1C—SATURATED FAT

2C –UNSATURATED FAT

3C --SATURATED FAT/ UNSATURATED FAT

Synthesis of Triglycerol

Site of synthesis -- > LIVER

Glycerol + ATP + glycerokinase Glycerol-3-p

Glycerol-3-p + Acyl CoA +Acyl transferase Monoacyl Glycerol-3-p

+CoASH

Monoacyl Glycerol-3-p + Acyl transferase Diacyl Glycerol-3-p +CoASH

Diacyl Glycerol-3-p + phosphatase +H2O Diglyceride

Diglyceride + Acyl CoA +Acyl transferase Triglyceride +CoASH

Diglyceride Triglycerol /phosphtidyl choline-phospholipid )

Adipose tissue –glycerokinase absent –glycerol cannot be utilized

There fore glycerol -3-P is needed to be synthesized .

Glucose -->DHAP--->GLYCEROL -3 P DEHYDROGENASE ) Glycerol-3-p

SYNTHESIS OF PHOSPHOLIPIDS

CHOLINE + ATP +CHOLINE KINASE >PHOSPHOCHOLINE +ADP+PI

PHOSPHOCHOLINE + CTP +PHOSPHOCHOLINE CYTIDYL TRANSFERASE

CDP - CHOLINE

CDP – CHOLINE + Diglyceride +PHOSPHOCHOLINE DIGLYCERIDE

TRANSFERASE PHOSPHOTIDYL CHOLINE + C-Amp

PHOSPHOTIDYL CHOLINE + PHOSPHOCHOLINE DIGLYCERIDE

TRANSFERASE LECITHINE

Abnormalities of lipid metabolism

Cachexia –opposite of obesity –failure to maintain normal lipid

stores –Higher rate of lipid mobilization than deposition

Anorexia Nervosa ---total loss of appetite (food plenty ) wealthy

women ,age group 10-30years (psychiatric disease )

Xanthomatosis ---Deposition of yellow –orange lipids in

liver ,spleen ,bone of skull,

Hyperlipedemia, hypercholesterolemia

OBESITY

DEFINITION :ABNORMAL INCREASE IN BODY WEIGHT DUE TO EXCESSIVE

DEPOSITION OF FAT

NUTITIONAL BASIS: OVER EATING (7 CAL IN EXCESS -1GM DEPOSITION OF

FAT) & LACK OF EXCERCISE

OBESE : INCREASE IN WEIGHT DUE TO FAT DEPOSITION IN ADIPOSE TISSUE

EXCEEDS MORE THAN 20-25% OF BOBY WEIGHT

TYPES OF OBESITY

JUVENILE

ADULT ONSET

GENETIC

HORMONAL RELATED

DRUG INDUCED

PSYCHIC

JUVENILE ONSET --- NUMBER OF ADIPOSE CELLS ARE INCREASED

ADULT ONSET --- NUMBER OF ADIPOSE CELLS CONSTANT BUT ENLARGE DUE TO EXCESSIVE DEPOSITION OF FAT (HYPERTROPIC OBESITY)

HORMONAL RELATED

CUSHING SYNDROME

HYPOTHYROISM

INSULINOMA

GENETIC DISPOSITION ---PLAY A SIGNIFICANT ROLE IN THE RISK OF OBESITY

OBESITY :DECREASED ABILITY OF THE BODY TO CONVERT THE METABOLIC FUEL TO HEAT ( LOW PROPORTION OF BROWN ADIPOSE TISSUE)

OBESITY

OBESITY WHITE ADIPOSE TISSUE---FAT STORED SIGNIFICANTLY ---TISSUE

IS METABOLICALLY LESS ACTIVE

BROWN ADIPOSE TISSUE

Fat storage not significant

Tissue is metabolically not active

Rich in mitochondria & cytochromes

low activity of ATP SYNTHASE

Active center for oxidation of fatty acids & glucose

Diet induced thermogenesis

oxidative phosphorylation & respiratory chain uncoupled (energy dissipated as heat) therefore blocks ATP formation

Present in hibernating animals & thoracic region of newborn & adult human

(brown adipose tissue is absent in obese person )

Fortunate to have brown adipose tissue x opposite of obesity

ATHEROSCLEROSIS

ATHER ----MUSH

THICKING OF ARTERIES DUE TO ACCUMULATION OF LIPIDS

FREE & ESTER CHOLESTEROL ,COLLAGEN ,FIBROUS TISSUE ,PROTEROGLYCANS

,CALCIUM DEPOSITS IN THE INNER WALLS-----MYCARDIAL INFARCTION

DISORDERS ASSOCIATED WITH ATHEROSCLEROSIS

DIEBETIS MELITUS

NEPHROTIC SYNDROME

HYPOTHYRODISM

+ OBESITY

+SMOKING

+ STRESS

HIGH LEVELS OF HDL = LOW INCIDENE OF CVD

REMEDY --- HEAVY EXCERCISE /CONSUMPTION OF UNSATURATED FATTY ACIDS

(VEGETABLE & FISH OILS)

REDUCION IN BODY WEIGHT

LIPOPROTEIN A & CORONARY HEART DISEASE

> 30mg/dl increases risk of CHD

STRUCTURE SIMILLAR TO LDL

INHIBITES FIBRINOLYSIS

CAUSES OF ATHEROSCEROSIS

INCREASED LDL

INCREASED VLDL

DECREASED HDL

CORONARY HEART DISEASE

MYOCARDIAL INFARCTION

ALCOHOL METABOLISM ALCOHOL ------ RELEVIES TENSION & ANXIETY

SMALL DOSES -----BENEFICIAL EFFECTS

HIGH DOSES ------HARMFUL EFFECTS

(PROLIFERATION OF SMOOTH ENDOPLASMIC RETICULUM

MAJOR PATHWAY--- MICROSOMAL ETHANOL OXIDISING SYSTEM(SMOOTH

ENDOPLASMIC RETICULUM)

ETHANOL + O2 +NADPH+ H + -------------------- ACETALDEHYDE + NADPH + 2H20

CYTOCHROME P450 REDUCTASE

MINOR PATHWAY (LIVER USING ALCOHOL DEHYDROGENASE )

ETHANOL +NAD + --------------- ACETALDEHYDE + NADH+ H+

ALCOHOL METABOLISM

ALCOHOL LEADS TO FATTY LIVER

ACETATE ACETYL CO A TCA CYCLE /FATTY ACID SYNTHESIS

ALCOHOL AGGREVATES GOUT

-----INCREASED NADH/NAD >>>INCREASED LACTIC ACID & ITS EXCRETION

DECREASED EXCRETION OF URIC ACID GOUT

ALCOHOL TOXICITY –ACTIVITY ALDEHYDE DEHYDROGENASE IS LESS THAN

ALCOHOL DEHYDROGENASE –ALDEHYDE GETS ACCUMULATED— VARIOUS

COMPLICATIONS

DISULFIRAM----DRUG UESD IN TREATMENT OF ALCOHOLISM INHIBITS ALDEHYDE

DEHYDROGENASE

ETHANOL +NAD+ +ALCOHOL DEHYDROGENASE >>>>ACETALDEHYDE +NADH +H +

ALDEHYDE +NAD + + ALDEHYDE DEHYDROGENASE>>ACETIC ACID+ NADH+ H +

SOURCE OF IMAGES--GOOGLE