LIPID METABOLISM

BYDR. MARYJANE.

LIPID CHARACTERISTIC

• Lipid = a compound that is insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform)

• “lipid” is synonymous with “fat• The bulk of dietary lipid is triglyceride (TG).• Also called triacylglycerol (TAG)• TAG is composed of: glycerol + 3-fatty acids

Triglyceride

DIGESTIONDIGESTION

Digestion Digestion → small particles→ small particles

End products of digestion:End products of digestion: Carbohydrates → Carbohydrates →

monosaccharidesmonosaccharides Proteins → amino acidsProteins → amino acids Fats → glycerol, fatty acidsFats → glycerol, fatty acids

Lipids DigestionLipids Digestion

The major portion of fat digestion The major portion of fat digestion takes place in the small intestine takes place in the small intestine as a result of pancreatic lipaseas a result of pancreatic lipase

The LiverThe Liver

Produces bile (fat digestion)Produces bile (fat digestion)

The GallbladderThe Gallbladder

Stores bileStores bile Concentrates itConcentrates it Releases to Releases to

small intestine small intestine when needed when needed via a hormonal via a hormonal signalsignal

FAT DIGESTION AND FAT DIGESTION AND ABSORPTIONABSORPTION

MouthMouth: no digestion takes place here: no digestion takes place here StomachStomach: fat digestion begins here with : fat digestion begins here with

30% of triglyceride being digested under 30% of triglyceride being digested under the influence of the enzyme the influence of the enzyme gastric lipase gastric lipase and lingual lipaseand lingual lipase

This partly digested food containing This partly digested food containing globules of fat and acidic fluid mixture globules of fat and acidic fluid mixture called chyme, passes from the stomach called chyme, passes from the stomach into the into the duodenumduodenum (where majority of fat (where majority of fat digestion takes place)digestion takes place)

While in the duodenum, a hormonal While in the duodenum, a hormonal signal causes the walls of the signal causes the walls of the gallbladder to contract rhythmically, gallbladder to contract rhythmically, squeezing the bile into the common squeezing the bile into the common bile duct into the duodenum.bile duct into the duodenum.

Left to the fat molecules, they would Left to the fat molecules, they would aggregate to form large globules that aggregate to form large globules that would only present a small surface area would only present a small surface area for pancreatic lipases to act.for pancreatic lipases to act.

Bile and mechanical mixing due to Bile and mechanical mixing due to peristalsis prevents this from peristalsis prevents this from happening, stabilizing the fat in small happening, stabilizing the fat in small globules called globules called micelles.micelles.

PancreasPancreas: It secretes bicarbonate : It secretes bicarbonate ions through the action of the ions through the action of the hormone hormone secretin secretin which help to which help to neutralize the pH of the chyme neutralize the pH of the chyme entering the duodenum from the entering the duodenum from the stomach cos lipase works best at stomach cos lipase works best at neutral pH.neutral pH.

it also produces the enzyme lipases it also produces the enzyme lipases called called pancreatic lipase pancreatic lipase which is which is essential in fat digestion through essential in fat digestion through stimulation by the hormone stimulation by the hormone CCKCCK..

Once stabilized in micelles by bile salts, Once stabilized in micelles by bile salts, the digestive enzyme from the pancreas the digestive enzyme from the pancreas called lipase can begin their work breaking called lipase can begin their work breaking down triglyceride into down triglyceride into fatty acids and fatty acids and 22- - monoacylglycerolmonoacylglycerol

This fatty acid and 2-monoacylglycerol This fatty acid and 2-monoacylglycerol with bile salts form what is called a mixed with bile salts form what is called a mixed micellemicelle

Because the products of digestion are lipid-Because the products of digestion are lipid-soluble, they are carried in the form of soluble, they are carried in the form of mixed micelles which are soluble in the mixed micelles which are soluble in the aqueous environment of intestinal lumen aqueous environment of intestinal lumen to the brush border membrane of to the brush border membrane of enterocytes where absorption takes place.enterocytes where absorption takes place.

The mixture of lipids absorbed by the The mixture of lipids absorbed by the enterocyte migrates to the endoplasmic enterocyte migrates to the endoplasmic reticulum where they are resynthesized into reticulum where they are resynthesized into triglycerides, combined with cholesteryl triglycerides, combined with cholesteryl esters and phospholipids & coated with a esters and phospholipids & coated with a protein to form protein to form chylomicronschylomicrons. .

The protein coat serves to make the The protein coat serves to make the chylomicron water-soluble & to facilitate chylomicron water-soluble & to facilitate exocytosisexocytosis

This chylomicron leaves the enterocyte and This chylomicron leaves the enterocyte and enter lymphatic vessels.enter lymphatic vessels.

From here, they are transported to the blood From here, they are transported to the blood via the thoracic duct then to left subclavian via the thoracic duct then to left subclavian vein to the body.vein to the body.

ABNORMALITY OF ABNORMALITY OF DIGESTION AND DIGESTION AND ABSORPTION OF FATABSORPTION OF FAT SteatorrheaSteatorrhea: excretion of fat in : excretion of fat in

fecesfeces SymptomsSymptoms: bulky, foul smelling : bulky, foul smelling

stool that floats.stool that floats.

β- OXIDATION OF SATURATED EVEN CHAIN FATTY ACIDS

• SITE: mitochondria• Is the process where energy is produced from lipids.

BETA OXIDATION

• β- oxidation involves four reactions:• 2 oxidation reaction• Hydration• Thiolysis

• Involves the removal of two-carbon acetyl CoA fragments from the carboxyl end of the fatty acid successively producing acetyl CoA, NADH and FADH₂.

• β- oxidation involves four reactions:• 2 oxidation reaction• Hydration• Thiolysis• These 4 steps are repeated for saturated fatty acids of

even-numbered carbon chains (n/2)-1 times. (where n is the number of carbons)

• Each cycle producing an acetyl group plus one NADH and one FADH₂.

• The final thiolytic cleavage produces two acetyl groups.

Palmitic Acid -ATP Synthesis• Palmitic Acid is C-16• Step 1 – FADH₂ = 2 ATP• Step 3 - NADH = 3 ATP • Total ATP = 5 ATP• Example with palmitic acid (16 C):• Number of turns of fatty acid spiral = 7 turns using the

formula (n/2)-1 while the number of acetyl CoA = 8 using the formula (n/2)

• This formula only applies for saturated fatty acids of even numbered carbon chains.

• NET ATP from contribution of NADH and FADH₂ = 35 ATP

• REMEMBER 8 acetyl CoA from the total turn is produced and this acetyl CoA enters into the citric acid cycle.

• Entrance of one acetyl CoA into the citric acid cycle yields 12 ATPs.

• Therefore 8 acetyl CoA entering into the citric acid cycle will give 8 x 12 ATPs = 96 ATPs.

• The total net energy from β- oxidation of palmitic acid will give 96 ATP +35 ATP =131-2 ATPS used in the activation of the fatty acid to its corresponding acylCoA = 129 ATPs.

Beta Oxidation

BETA OXIDATION OF ODD CHAIN FATTY ACIDS

• Beta-oxidation of odd chain fatty acids follows the same pattern as that for even chain, but yields propionyl-CoA (3C) unlike beta-oxidation of even chain fatty acids which yields acetyl CoA (2C)

How Are Odd-Carbon Fatty Acid Oxidized?

-oxidation yields propionyl-CoA

• Odd-carbon fatty acids are metabolized normally, until the last three-C fragment - propionyl-CoA - is reached

• Three reactions convert propionyl-CoA to succinyl-CoA

• biotin and Vitamin B12 are required

• Succinyl CoA produced here can go into kreb cycle to yield energy(ATP).

• Deficiency of vitamin B12: results in excretion of propionate and methylmalonate in the urine.

• Methylmalonic acidemia and aciduria: due to deficiency of methylmalonyl CoA mutase OR pt is unable to convert B12 into its coenzyme form(deoxyadenosyl cobalamin).

• Symptoms: results in metabolic acidosis with developmental retardation, vomiting, lethargy, hepatomegaly,coma and death.

Ketone bodies• Are produced as by-products when fatty acids are

broken for energy in the liver.• Produced by the liver mitochondria using acetyl

CoA derived from fatty acid oxidation.• Are of 3 types: acetoacetate, acetone & beta-

hydroxybutyric acid.

Production and utilization of ketone bodies

• They are a vital source of energy for the brain during prolonged fasting.

• Over-production of ketone bodies is referred to as ketosis.

• One sign of ketosis is the odor of acetone on the breath. This occurs in a form of diabetes (type 1) most commonly but can also occur minimally in type 2

DIABETES

• Is a condition of excess blood glucose as a result of

• 1. lack of insulin to bring down the blood glucose

• 2. obesity that impairs insulin uptake in cells

DIABETES• Are two types• Type 1: called insulin dependent diabetes mellitus (IDDM), its as a

result of lack of insulin due to destruction of the beta cells of the pancreas

• Onset is early childhood• Treatment: insulin

• Type 2: called non-insulin dependent diabetes mellitus (NIDDM).• Its due to obesity impairing uptake of insulin by cells OR not

enough insulin being produced by the beta cells of the pancreas• Onset is adulthood• Have a genetic component to it• TREATMENT: drugs +/- insulin• Symptoms: polydipsia, polyphagia, polyuria, weight gain(type 2)

Diabetic ketoacidosis (DKA)

• Diabetic ketoacidosis is a complication of diabetes that occurs when the body cannot use sugar (glucose) as a fuel source because the body has no insulin or not enough insulin, and fat is used instead. Byproducts of fat breakdown, called ketones, build up in the body.

• People with type 1 diabetes lack insulin, a hormone the body uses to process glucose (blood sugar) for energy. When glucose is not available, fatty acid is broken down instead

• As fats are broken down, acids called ketones build up in the blood and urine. In high levels, ketones are poisonous. This condition is known as ketoacidosis

• Blood glucose levels rise (usually higher than 300 mg/dL) because the liver produces glucose to try to combat the problem. However the cells cannot pull in that glucose without insulin.

Symptoms of diabetic ketoacidosis (DKA)

• The warning signs that you are becoming very sick might include:

• Deep, rapid breathing• Dry skin and mouth (dehydration)• Flushed face• Fruity breath (breath odor) indicative of acetone • Nausea and vomiting• Stomach pain• As well as increase in blood glucose level

TREATMENT OF DKA

• Insulin therapy• Fluid replacement to combat the dehydration.