CLINICAL ASPECT

1. Allergic responses and arthritic conditions: Released enzymes from ruptured lysosomal membra
(substrates) leading to tissue damage in many types of allergic responses and arthritic conditions.

In Gout: Urate crystals are deposited around joints. These crystals when phagocytosed cause physica
enzymes producing inflammation and arthritis.

2. Inherited disorders: A number of hereditary diseases involving the abnormal accumulation of comp
afflicted individual have now been traced to the absence of key acid hydrolases in the lysosomes of the

3. I-Cell disease: I-cell disease is a rare condition in which lysosomes lack all of the normal lysosomal

• The disease is characterised by severe progressive psychomotor retardation and a variety of physica
first decade. 


• Cultured cells from patients with I-cell disease was found to lack almost all of the normal lysosomal e
many different types of undegraded molecules forming inclusion bodies. 


• Samples of plasma from patients with the disease were observed to contain very high activities of lys
enzymes were being synthesised but failed to reach their proper intracellular locations and we

• Mannose-6-P is the marker. Studies have shown that lysosomal enzymes from patients with I-cell d
cells from patients with I-cell disease found to be deficient in the enzyme GlcNAc phosphotran
of GlcNAc-1-P in specific mannose residues of certain lysosomal enzymes. Hence they can not
events in genesis of I-cell disease: 
 Mutations in DNA 
 
 Mutant GlcNAc phosphotransfer
GlcNAc-1-P to specific mannose residues of certain enzymes destined for lysosomes 
 


6. Peroxisomes: Peroxisomes are small organelles also called Microbodies, present

in eukaryotic cell. The parti- cles are approximately 0.5 in diameter. These
subcellular respiratory organelles have no energy-coupled electron transport
systems and are probably formed by budding from smooth endoplasmic reticulum (ER).

Functions

. (i) They carryout oxidation reactions in which toxic 
 hydrogen peroxide

(H2O2) is produced, which is 
 destroyed by the enzyme catalase. 


. (ii) Recentlyithasbeenshownthatliverperoxisomes 
 have an unusually active

-oxidative system capable of oxidising long chain fatty acids (C 16 to 18
or > C 18) 


The -oxidation enzymes of peroxisomes are rather unique in that the first step
of the oxidation is catalysed by a flavoprotein, an “acyl Co-A oxidase”
Acyl-CoA + O2 , unsaturated acyl-CoA + H2O2

H2O2 produced is destroyed by catalase.

Peroxisomes may be absent in inherited disorder Zellweger’s syndrome (Refer to

Chapter on fatty acid oxidation).

7. Cytoskeleton: For many years, biochemists have considered the cytosol a

compartment containing soluble enzymes, metabolites and salts in an aqueous
but gel like environment.

Studies now support the idea that this compartment contains actually a complex
network of fine structures called (a) microtubules, (b) microfilaments and (c)
microtrabeculae.

(a) Microtubules: They are long unbranched slender cylindrical structures with an
average diameter of about 25 nm. The structures are made primarily by the self-
assembly of the heterodimer, tubulin having molecular weight 50,000.

Functions

• An important function of microtubules is their role in the assembly and

disassembly of the spindle structures during mitosis.