Ganong's Review of Medical Physiology, 23rd Edition

26 SECTION ICellular & Molecular Basis of Medical Physiology

mucosa where large lipoprotein complexes, chylomicrons,
are formed. The chylomicrons and their remnants constitute
a transport system for ingested exogenous lipids (exogenous
pathway). Chylomicrons can enter the circulation via the
lymphatic ducts. The chylomicrons are cleared from the cir-
culation by the action of lipoprotein lipase, which is located
on the surface of the endothelium of the capillaries. The
enzyme catalyzes the breakdown of the triglyceride in the
chylomicrons to FFA and glycerol, which then enter adipose

cells and are reesterified. Alternatively, the FFA can remain in

the circulation bound to albumin. Lipoprotein lipase, which

requires heparin as a cofactor, also removes triglycerides

from circulating very low density lipoproteins (VLDL).

Chylomicrons depleted of their triglyceride remain in the

circulation as cholesterol-rich lipoproteins called chylomi-

cron remnants, which are 30 to 80 nm in diameter. The rem-

nants are carried to the liver, where they are internalized and

degraded.

CLINICAL BOX 1–3

Diseases Associated with Imbalance of β-oxidation of Fatty Acids

Ketoacidosis and even fatal. Three conditions lead to deficient intracellular

glucose supplies, and hence to ketoacidosis: starvation; diabetes

mellitus; and a high-fat, low-carbohydrate diet. The acetone odor

on the breath of children who have been vomiting is due to the

ketosis of starvation. Parenteral administration of relatively small

amounts of glucose abolishes the ketosis, and it is for this reason

that carbohydrate is said to be antiketogenic.

Carnitine Deficiency

Deficient β-oxidation of fatty acids can be produced by carnitine

deficiency or genetic defects in the translocase or other enzymes

involved in the transfer of long-chain fatty acids into the mito-

chondria. This causes cardiomyopathy. In addition, it causes hy-

poketonemic hypoglycemia with coma, a serious and often

fatal condition triggered by fasting, in which glucose stores are

used up because of the lack of fatty acid oxidation to provide en-

ergy. Ketone bodies are not formed in normal amounts because

of the lack of adequate CoA in the liver.

The normal blood ketone level in humans is low (about 1

mg/dL) and less than 1 mg is excreted per 24 h, because the

ketones are normally metabolized as rapidly as they are

formed. However, if the entry of acetyl-CoA into the citric acid

cycle is depressed because of a decreased supply of the prod-

ucts of glucose metabolism, or if the entry does not increase

when the supply of acetyl-CoA increases, acetyl-CoA accumu-

lates, the rate of condensation to acetoacetyl-CoA increases,

and more acetoacetate is formed in the liver. The ability of the

tissues to oxidize the ketones is soon exceeded, and they accu-

mulate in the bloodstream (ketosis). Two of the three ketone

bodies, acetoacetate and β-hydroxybutyrate, are anions of the

moderately strong acids acetoacetic acid and β-hydroxybutyric

acid. Many of their protons are buffered, reducing the decline

in pH that would otherwise occur. However, the buffering

capacity can be exceeded, and the metabolic acidosis that

develops in conditions such as diabetic ketosis can be severe

TABLE 1–5 The principal lipoproteins.*

Composition (%)

Lipoprotein Size (nm) Protein

Free

Cholesteryl

Cholesterol

Esters Triglyceride Phospholipid Origin

Chylomicrons 75–1000 2 2 3 90 3 Intestine

Chylomicron remnants 30–80 ... ... ... ... ... Capillaries

Very low density lipoproteins

(VLDL)

30–80 8 4 16 55 17 Liver and intestine

Intermediate-density lipo-

proteins (IDL)

25–40 10 5 25 40 20 VLDL

Low-density lipoproteins

(LDL)

20 20 7 46 6 21 IDL

High-density lipoproteins

(HDL)

7.5–10 50 4 16 5 25 Liver and intestine

*The plasma lipids include these components plus free fatty acids from adipose tissue, which circulate bound to albumin.