Ethyl alcohol was first isolated in pure form in 1820 by Jean Dumas, who has also noticed the clinical effect of chronic alcoholism. Most of alcohol is absorbed by intestine. About 1% of the ingested alcohol is excreted through the lungs or urine. Major fraction of the alcohol is oxidized in the liver.
1. Alcohol Dehydrogenase (ADH)
It is an NAD+ dependent cytoplasmic enzyme. It oxidizes
ethanol to acetaldehyde (Fig. 7.6). In some individuals the enzyme is mutated. This mutation rate is more in orientals. In
such individuals, alcohol metabolism is slower and even small quantity of alcohol may produce symptoms of intoxication.
2. Aldehyde Dehydrogenase
T he acetald eh yd e is furth er o xidized to acetate b y a
mitochondrial NAD+ dependent enzyme (Fig. 7.6). The acetate
is then converted to acetyl-CoA pathway. The activity of alcohol dehydrogenase is more than aldehyde dehydrogenase. So acetaldehyde accumulates in liver. Aldehyde is toxic, which in excess may lead to cell death. The activity of aldehyde d eh yd ro genase is less in In dian s, when co mp ared to Europeans.
3. Biochemical Alterations in Alcoholism
i. Both the oxidation steps of alcohol produces NADH. The high NADH level favors conversion of pyruvate to lactate, leading to lactic acidosis.
ii. Deficiency of pyruvate leads to inadequate formation of oxaloacetate. This results in depression of gluconeo- genesis, leading to hypoglycemia.
iii. Increased level of acetyl CoA causes increased fatty acid synth esis; bu t fatty acid is n ot oxidized. So fat is accumulated in liver, resulting in fatty liver.
iv. Accumulated toxic effect of acetaldehyde leads to cellular death. This is followed by replacement by fibrous tissue. Fibrosis of liver is called cirrhosis. When liver functions are reduced, hepatic coma results.
v. Five percent of all deaths in India are due to liver diseases, for which the most important culprit is alcohol. In India, chronic alcoholism is the most leading cause for morbidity and consequent loss of man hours. Indians are more prone
for alcoholic cirrhosis.
vi. Alcohol causes CNS depression by inhibiting excitatory receptors and by potentiating inhibitory neurotransmitter (GABA) receptors.
vii. In chronic alcoholics, the brain neurons are lost, neuro- degenerative changes set in, and the memory is affected. In alcoholics, combined thiamine deficiency leads to
Wernicke's disease.
Mucopolysaccharidoses
These are a group of inborn errors of metabolism characterized by excessive intralysosomal accumulation of glucosamino glycans (GAG) in various tissues. They are progressive disorders. Most of these diseases are inherited as autosomal recessive traits.
The clinical manifestations include coarse facial features, thick skin and corneal opacity due to accumulation of GAG. Mental retardation, growth deficiency and skeletal dysplasia are also seen due to defective cell function. In general, defective degradation of heparan sulfate leads to mental retardation predominantly whereas accumulation of other GAGs leads to mesenchymal abnormalities.
The inborn errors associated with carbohydrate metabolism, are shown in Table 7.1.
Table 7.1: Inborn errors associated with carbohydrate metabolism (*)
Name Incidence Defective enzyme Chromosome Salient features Chapter
1 out of location no.
Lactose intolerance Lactase Milk induced diarrhea 4
Fructose intolerance 20,000 Aldolase B 9 Hypoglycemia, vomiting, 7
hepatomegaly
Fructosuria 130,000 Fructokinase Benign; urine sugar 7
Galactosemia 35,000 Gal-1-P-uridyl transferase 9 Hypoglycemia; hepato- 7
megaly; mental retardation;
jaundice; congenital cataract
Essential pentosuria 2,500 Xylitol dehydrogenase Benign 7
GPD deficiency 5,000 Glucose-6-phosphate X-link Drug-induced hemolytic 7
dehydrogenase anemia
(*) Glycogen storage diseases are important inborn errors associated with carbohydrate metabolism; these are shown in Table 5.7.
Fig. 7.6: Alcohol metabolism
A QUICK LOOK
• The HMP shunt pathway (Pentose Phosphate pathway) generates NADPH required for reductive biosynthesis of steroids, fatty acids and cholesterol. • It also provides pentose sugars (Ribose and
Deoxyribose) for nucleic acid synthesis.
• Glucuronic acid is used for conjugation of bilirubin, steroids and drugs.
• In lower animals, ascorbic acid (vitamin C) is synthesised by the glucuronic acid pathway; but human beings, could not synthezise vitamin C.
• Hereditary fructose intolerance is due to the deficiency of the enzyme, aldolase-B.
• Galactose is necessary for synthesis of lactose (milk sugar).
• Galactosemia is due to the deficiency of galactose- 1-phosphate uridyl transferase enzyme.
• Important manifestations of galactosemia are: mental retardation, congenital cataract, hepatomegaly, and galactosuria.
• Lactose free diet is the treatment policy for galactosemia.
• Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase.
• Aldehyde generated from alcohol is toxic to liver cells; fatty liver and cirrhosis results.
• Alcohol inhibits CNS. Chronic use of alcohol will lead to degeneration of brain.
CHAPTER AT A GLANCE
The reader will be able to answer questions on the following topics:
1. Functions and composition of saliva 2. Alterations in composition in diseases 3. Composition of teeth
4. Collagen and other proteins in teeth 5. Dental caries, plaque
6. Microorganisms causing caries 7. Sucrose and caries
8. Fluoride prevents caries 9. Fluorosis
Saliva is the biological fluid, which bathes the oral cavity. It is a complex fluid produced by a number of specialized glands which discharge into the oral cavity. Saliva contains electrolytes and proteins with an osmolality less than or equal to that of plasma. Some amount of cell debris arising from the epithelial cells of the mouth are also constituents of saliva.
The total volume of saliva produced each day in adults is 500 to 1500 ml. Mixed saliva consists of the secretions of submandibular (65%), parotid (20%), and sublingual (5%) glands, the remaining 10% being provided by the numerous small labial, buccal, and palatal glands which line the mouth.
The glandular tissue is comprised of acinar cells, specialized groups of cells arranged as end pieces surrounding a small central lumen that opens into a narrow intercalated duct. Such ducts lead to the striated ducts, that in turn drain into the secretory ducts to form a single main secretory duct which drains into the oral cavity.
Functions of Saliva
i. Antibacterial and antifungal action ii. Buffering
iii. Digestion iv. Mineralization
v. Lubrication.
vi. Many salivary components do multiple jobs. For example, amylase in addition to being an enzyme also inhibits precipitation of calcium salts.
Composition of Saliva
i. Saliva is not a simple ultrafiltrate of plasma, but rather a complex fluid formed by different mechanisms such as (a) passive diffusion, (b) active process against a concentration gradient and (c) ultrafiltration through pores in the membrane.
ii. An active transport mechanism operates for many electrolytes and for some proteins such as IgA. Small molecules can be transported via the ultrafiltration route. Changes in plasma composition or components of diet have little effect on salivary constituents.
iii. The parotid glands produce serous secretions only, devoid of mucin. On the other hand, the submandibular and sublingual glands secrete both serous and mucinous secretions.
iv. The viscosity of the submandibular saliva usually decreases with increasing flow rate since the serous cells have a greater response to stimulation than do the mucin-secreting cells. v. The sublingual gland contains predominantly mucin-secreting cells and thus their secretion has a thick, viscous nature.
vi. Salivary secretion is stimulated by smell and taste. The regulatory centers are in pons in brain. Salivary secretion is a reflex response controlled by both parasympathetic and sympathetic secretomotor nerves. Stimulation of the sympathetic trunk in the neck or injection of epinephrine causes secretion by the submaxillary but not by the parotid glands. Parasympathomimetic drugs cause high saliva flow.