Clinical Aspects

Deficiency of Lung Surfactant Causes Respiratory Distress Syndrome

Lung surfactant is composed mainly of lipid with some proteins and carbohydrate and prevents the alveoli from collapsing. Surfactant activity is largely attributed to dipalmitoylph osphatidylcholine, which is synthesized shortly before parturition in full-term infants. Deficiency of lung surfactant in the lungs of many preterm newborns gives rise to respiratory distress syndrome. Administration of either natural or artificial surfactant has been of therapeutic benefit.

Phospholipids & Sphingolipids Are Involved in Multiple Sclerosis and Lipidoses

Certain diseases are characterized by abnormal quantities of these lipids in the tissues, often in the nervous system. They may be classified into two groups: (1) true demyelinating diseases and (2) sphingolipidoses.

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels.

The sphingolipidoses (lipid storage diseases) are a group of inherited diseases that are often manifested in childhood. These diseases are part of a larger group of lysosomal disorders and exhibit several constant features: (1) Complex lipids containing ceramide accumulate in cells, particularly neurons, causing neurodegen-

A Ceramide -^y -Sphingomyelin

Phosphatidylcholine Diacylglycerol

Figure 24-8. Biosynthesis of sphingomyelin (A), UDPGal udp PAPS Sulfogalactosyl- galactosylceramide and its sulfo derivative (B). (PAPS, V J Galactosylceramide V ceramide "active sulfate," adenosine 3'-phosphate-5'-phospho-B Ceramide —^—»- (cerebroside) -^—>- (sulfatide) sulfate.)






Cer-Glc-Gal I


UDP-N-acetyl -galactosamine


Higher gangliosides (disialo- and trisialo-gangliosides)

Cer-Glc-Gal-GalNAc-Gal I


Cer-Glc-Gal-GalNAc I


Figure 24-9. Biosynthesis of gangliosides. (NeuAc, W-acetylneuraminic acid.)

eration and shortening the life span. (2) The rate of synthesis of the stored lipid is normal. (3) The enzymatic defect is in the lysosomal degradation pathway of sphingolipids. (4) The extent to which the activity of the affected enzyme is decreased is similar in all tissues. There is no effective treatment for many of the diseases, though some success has been achieved with enzymes that have been chemically modified to ensure binding to receptors of target cells, eg, to macrophages in the liver in order to deliver P-glucosidase (glucocerebrosi-

dase) in the treatment of Gaucher's disease. A recent promising approach is substrate reduction therapy to inhibit the synthesis of sphingolipids, and gene therapy for lysosomal disorders is currently under investigation. Some examples of the more important lipid storage diseases are shown in Table 24-1.

Multiple sulfatase deficiency results in accumulation of sulfogalactosylceramide, steroid sulfates, and proteoglycans owing to a combined deficiency of aryl-sulfatases A, B, and C and steroid sulfatase.

Table24-1. Examples of sphingolipidoses.


Enzyme Deficiency

Lipid Accumulating1

Clinical Symptoms

Tay-Sachs disease

Hexosaminidase A

Cer-Glc-Gal(NeuAc)-GalNAc GM2Ganglioside

Mental retardation, blindness, muscular weakness.

Fabry's disease


Skin rash, kidney failure (full symptoms only in males; X-linked recessive).

Metachromatic leukodystrophy


Mental retardation and psychologic disturbances in adults; demyelination.

Krabbe's disease


Mental retardation; myelin almost absent.

Gaucher's disease


Enlarged liver and spleen, erosion of long bones, mental retardation in infants.

Niemann-Pick disease




Enlarged liver and spleen, mental retardation; fatal in early life.

Farber's disease


Acyl-Sphingosine Ceramide

Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life.

1NeuAc, N-acetylneuraminic acid; Cer, ceramide; Glc, glucose; Gal, galactose. —-, site of deficient enzyme reaction.

1NeuAc, N-acetylneuraminic acid; Cer, ceramide; Glc, glucose; Gal, galactose. —-, site of deficient enzyme reaction.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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