Biochem FA catabolism

Most of the “fats” in diet and in

adipose tissue are

• major form of stored energy in the body

triglycerides

Hormones (glucagon, epinephrine,

ACTH)

trigger the release of fatty acids from adipose tissue

The carbon in fatty acids (mostly -CH2-) is _____ (so its oxidation yields the most energy possible).

reducded

Fatty acids are ______ (as mono- and polysaccharides are), so they can pack more closely in storage tissues

not hydrated

Because of their insolubility, fats are usually emulsified with _____ or

complexed with proteins as

bile salts, lipoproteins

Prmary sources of TAGS

• Diet

• De novo biosynthesis in the liver

• Storage depots in adipocytes

Dietary fatty acids are absorbed in the

vertebrate small intestine

Bile Salts Emulsify TAGs in the

intestine

fatty acids combine with bile salts in mixed micelles, which deliver fatty acids to the epithelial cells that

cover the intestinal villi. This happens in the ____________________

small intestine

Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into

lipoprotein aggregates termed ______

chylomicrons

cleave fatty acids at the C-1 and C-3 positions.

pancreatic lipases

MAG

monoacylglycerol

CE

cholesterol esterase

LPL

lipoprotein lipase

PL

pancreatic lipase

Obesity

• 1/3 of Americans

• Medical costs estimated at $147 billion

• Linked with changes in metabolism & inflammation

Fat in the diet is carried through the circulation either as

• Serum albumin-bound FFA

• Or in TG-rich lipoproteins, which release FFA to cells through the action of lipoprotein lipases

Circulating FAs are taken up by the endothelial cells lining blood vessel walls and

bind to cytosolic

FA binding proteins

Waist circumference cut points of men

>102 cm (>40 in.)

• substantially increased” risk

Waist circumference cut points of women

>88 cm (>35 in.

• substantially increased” risk

>94 cm in men

increased risk

>80 cm in women

increased risk

high levels of circulating FFA lead to

altered deposition and accumulation of TGs in liver, muscle, and adipose tissue

Adipose tissue is not only involved in energy storage But also functions as

endocrine organ that plays a key role in integration of system metabolism by secreting a variety of

signaling proteins

adipokines

Proteins secreted by adipose tissue are collectively termed

The two most abundant depots are

visceral and subcutaneous adipose tissues

Adipokines may be

inflammatory or anti-inflammatory

Mobilization of stored fat (lipolysis) is hormonally controlled via

cAMP

• Epinephrine during stress

situations

• Glucagon during fasting

Human serum albumin, at 40 mg/mL

• most abundant protein in the bloodstream

• It provides 80% of the osmotic pressure of blood plasma

• It is the major macromolecular anion in blood and has important buffering capacity

• It is the major transport vehicle for hydrophobic substances, such as fatty acids

FFA solubility in blood

= 0.1 nM

[FFA], as bound to serum albumin,

approaches 1 mM

Glycerol kinase

• activates glycerol at the expense of ATP

• Muscle and adipose do NOT have- liver does

Fats are degraded into FA and glycerol in the

cytoplasm of adipocytes

β-oxidation of fatty acids occurs in

mitochondria

Larger fatty acids (most free fatty acids) are transported via

acyl-carnitine/carnitine transporter

Very-long-chain (VLCFA)

22 carbons +

Long chain (LCFA)

13-21 carbons

Medium-chain

6-12 carbons

Short-chain (SCFA)

≤5 carbons

Step 1: CoA activates FAs for oxidation

Acyl-CoA synthetase condenses fatty acids with CoA, with

simultaneous hydrolysis of ATP to AMP and PP

Carnitine

carries fatty acyl groups across the mitochondrial membranes

SCFAs are carried directly into

the mitochondrial matrix

LCFAs

• converted to acyl-carnitines and are then transported into the mitochondria

• attached to form fatty acyl-carnitine via Carnitine palmitoyltransferase 1(CPT1) or carnitine acyltransferase 1(CAT1)

Acyl-CoA esters are formed inside the inner mitochondrial membrane from

transported acylcarnitine

Step 2: Transport into Mitochondria

• Carnitine synthesized from lysine and methionine

1. Transesterification of fatty acids to carnitine

2. Transport into mitochondria matrix

3. Transesterification back to coenzyme A

β-Oxidation of Fatty Acids A Repeated Sequence of 4 Reactions Strategy

• create a carbonyl group at the β-C

• First 3 reactions do that

• fourth cleaves the “β-keto ester" in a reverse Claisen condensation

β-Oxidation of Fatty Acids products

an acetyl-CoA and a fatty acid two carbons shorter