Ganong's Review of Medical Physiology, 23rd Edition

24 SECTION ICellular & Molecular Basis of Medical Physiology

the liver, they diffuse into the circulation. Acetoacetate is also
formed in the liver via the formation of 3-hydroxy-3-methyl-
glutaryl-CoA, and this pathway is quantitatively more impor-
tant than deacylation. Acetoacetate, β-hydroxybutyrate, and
acetone are called ketone bodies. Tissues other than liver
transfer CoA from succinyl-CoA to acetoacetate and metabo-
lize the “active” acetoacetate to CO 2 and H 2 O via the citric
acid cycle. Ketone bodies are also metabolized via other path-
ways. Acetone is discharged in the urine and expired air. An
imbalance of ketone bodies can lead to serious health prob-
lems (Clinical Box 1–3).

CELLULAR LIPIDS

The lipids in cells are of two main types: structural lipids,

which are an inherent part of the membranes and other parts

of cells; and neutral fat, stored in the adipose cells of the fat

depots. Neutral fat is mobilized during starvation, but struc-

tural lipid is preserved. The fat depots obviously vary in size,

but in nonobese individuals they make up about 15% of body

weight in men and 21% in women. They are not the inert

structures they were once thought to be but, rather, active dy-

namic tissues undergoing continuous breakdown and resyn-

thesis. In the depots, glucose is metabolized to fatty acids, and

neutral fats are synthesized. Neutral fat is also broken down,

and free fatty acids are released into the circulation.

A third, special type of lipid is brown fat, which makes up a

small percentage of total body fat. Brown fat, which is some-

what more abundant in infants but is present in adults as well,

is located between the scapulas, at the nape of the neck, along

the great vessels in the thorax and abdomen, and in other

scattered locations in the body. In brown fat depots, the fat

cells as well as the blood vessels have an extensive sympathetic

innervation. This is in contrast to white fat depots, in which

some fat cells may be innervated but the principal sympa-

thetic innervation is solely on blood vessels. In addition, ordi-

nary lipocytes have only a single large droplet of white fat,

whereas brown fat cells contain several small droplets of fat.

Brown fat cells also contain many mitochondria. In these

mitochondria, an inward proton conductance that generates

ATP takes places as usual, but in addition there is a second

proton conductance that does not generate ATP. This “short-

circuit” conductance depends on a 32-kDa uncoupling pro-

tein (UCP1). It causes uncoupling of metabolism and genera-

tion of ATP, so that more heat is produced.

PLASMA LIPIDS & LIPID TRANSPORT

The major lipids are relatively insoluble in aqueous solutions

and do not circulate in the free form. Free fatty acids (FFAs)

are bound to albumin, whereas cholesterol, triglycerides, and

phospholipids are transported in the form of lipoprotein

complexes. The complexes greatly increase the solubility of

the lipids. The six families of lipoproteins (Table 1–5) are

graded in size and lipid content. The density of these lipopro-

teins is inversely proportionate to their lipid content. In

general, the lipoproteins consist of a hydrophobic core of tri-

glycerides and cholesteryl esters surrounded by phospholipids

and protein. These lipoproteins can be transported from the

intestine to the liver via an exogenous pathway, and between

other tissues via an endogenous pathway.

Dietary lipids are processed by several pancreatic lipases in

the intestine to form mixed micelles of predominantly FFA,

2-monoglycerols, and cholesterol derivatives (see Chapter

27). These micelles additionally can contain important

water-insoluble molecules such as vitamins A, D, E, and K.

These mixed micelles are taken up into cells of the intestinal

TABLE 1–4. Lipids.

Typical fatty acids:

Triglycerides (triacylglycerols): Esters of glycerol and three fatty acids.

R = Aliphatic chain of various lengths and degrees of saturation.

Phospholipids:

A. Esters of glycerol, two fatty acids, and

1. Phosphate = phosphatidic acid


2. Phosphate plus inositol = phosphatidylinositol


3. Phosphate plus choline = phosphatidylcholine (lecithin)


4. Phosphate plus ethanolamine = phosphatidyl-ethanolamine
   (cephalin)


5. Phosphate plus serine = phosphatidylserine
   B. Other phosphate-containing derivatives of glycerol
   C. Sphingomyelins: Esters of fatty acid, phosphate, choline, and the
   amino alcohol sphingosine.
   Cerebrosides: Compounds containing galactose, fatty acid, and sphin-
   gosine.
   Sterols: Cholesterol and its derivatives, including steroid hormones,
   bile acids, and various vitamins.

Palmitic acid: CH 5 (CH 2 ) 14 —C—OH

O

Stearic acid: CH 5 (CH 2 ) 16 —C—OH

O

Oleic acid:

(Unsaturated)

CH 5 (CH 2 ) 7 CH=CH(CH 2 ) 7 —C—OH

O

CH 2 —O—C—R CH 2 OH

CHOH + 3HO—C—R

CH 2 OH

Glycerol

O

CH 2 —O—C—R + 3H 2 O

CH 2 —O—C—R

Triglyceride

O

O

O