NEET MDS Lessons
Biochemistry
CLINICAL SIGNIFICANCE OF ENZYMES
The measurement of enzymes level in serum is applied in diagnostic application
Pancreatic Enzymes
Acute pancreatitis is an inflammatory process where auto digestion of gland was noticed with activation of the certain pancreatic enzymes. Enzymes which involves in pancreatic destruction includes α-amylase, lipase etc.,
1. α-amylase (AMYs) are calcium dependent hydrolyase class of metaloenzyme that catalyzes the hydrolysis of 1, 4- α-glycosidic linkages in polysaccharides. The normal values of amylase is in range of 28-100 U/L. Marked increase of 5 to 10 times the upper reference limit (URL) in AMYs activity indicates acute pancreatitis and severe glomerular impairment.
2. Lipase is single chain glycoprotein. Bile salts and a cofactor called colipase are required for full catalytic activity of lipase. Colipase is secreted by pancreas. Increase in plasma lipase activity indicates acute pancreatitis and carcinoma of the pancreas.
Liver Enzymes
Markers of Hepatocellular Damage
1. Aspartate transaminase (AST) Aspartate transaminase is present in high concentrations in cells of cardiac and skeletal muscle, liver, kidney and erythrocytes. Damage to any of these tissues may increase plasma AST levels.
The normal value of AST for male is <35 U/ L and for female it is <31 U/L.
2. Alanine transaminase (ALT) Alanine transaminase is present at high concentrations in liver and to a lesser extent, in skeletal muscle, kidney and heart. Thus in case of liver damage increase in both AST and ALT were noticed. While in myocardial infarction AST is increased with little or no increase in ALT.
The normal value of ALT is <45 U/L and <34 U/L for male and female respectively
Markers of cholestasis
1. Alkaline phosphatases
Alkaline phosphatases are a group of enzymes that hydrolyse organic phosphates at high pH. They are present in osteoblasts of bone, the cells of the hepatobiliary tract, intestinal wall, renal tubules and placenta.
Gamma-glutamyl-transferase (GGT) Gamma-glutamyl-transferase catalyzes the transfere of the γ–glutamyl group from peptides. The activity of GGT is higher in men than in women. In male the normal value of GGT activity is <55 U/L and for female it is <38 U/L.
2. Glutamate dehydrogenase (GLD) Glutamate dehydrogenase is a mitochondrial enzyme found in liver, heart muscle and kidneys.
Muscle Enzymes
1. Creatine Kinase Creatine kinase (CK) is most abundant in cells of brain, cardiac and skeletal.
2. Lactate Dehydrogenase
Lactate dehydrogenase (LD) catalyses the reversible interconversion of lactate and pyruvate.
Carbohydrates (glycans) have the basic composition
- Monosaccharides - simple sugars, with multiple hydroxyl groups. Based on the number of carbons (e.g., 3, 4, 5, or 6) a monosaccharide is a triose, tetrose, pentose, or hexose, etc.
- Disaccharides - two monosaccharides covalently linked
- Oligosaccharides - a few monosaccharides covalently linked.
- Polysaccharides - polymers consisting of chains of monosaccharide or disaccharide units
The pH scale
An acidic solution is one in which [H+ ] > [OH- ]
•In an acidic solution, [H+ ] > 10-7 , pH < 7.
•A basic solution is when [OH- ] > [H+ ].
•In a basic solution, [OH- ] > 10-7 , pOH < 7, and pH >7.
• When the pH = 7, the solution is neutral.
•Physiological pH range is 6.5 to 8.0
CHOLESTEROL AND ITS IMPORTANCE
Cholesterol is an important lipid found in the cell membrane. It is a sterol, which means that cholesterol is a combination of a steroid and an alcohol .
It is an important component of cell membranes and is also the basis for the synthesis of other steroids, including the sex hormones estradiol and testosterone, as well as other steroids such as cortisone and vitamin D.
In the cell membrane, the steroid ring structure of cholesterol provides a rigid hydrophobic structure that helps boost the rigidity of the cell membrane.
Without cholesterol the cell membrane would be too fluid. In the human body, cholesterol is synthesized in the liver.
Cholesterol is insoluble in the blood, so when it is released into the blood stream it forms complexes with lipoproteins.
Cholesterol can bind to two types of lipoprotein, called high-density lipoprotein (HDL) and low-density lipoprotein (LDL).
A lipoprotein is a spherical molecule with water soluble proteins on the exterior. Therefore, when cholesterol is bound to a lipoprotein, it becomes blood soluble and can be transported throughout the body.
HDL cholesterol is transported back to the liver. If HDL levels are low, then the blood level of cholesterol will increase.
High levels of blood cholesterol are associated with plaque formation in the arteries, which can lead to heart disease and stroke.
Monosaccharides: Aldoses (e.g., glucose) have an aldehyde at one end
They are classified acc to the number of carbon atoms present
Trioses, tetroses, pentose ( ribose, deoxyribose), hexoses (glucose, galactose, fructose) Heptoses (sedoheptulose)
Glyceraldehyde simplest aldose
Ketoses (e.g., fructose) have a keto group, usually at C 2.
Dihydroxyacetone simplest Ketoses
The higher sugar exists in ring form rather than chain form
Furan : 4 carbons and 1 oxygen
Pyrans : 5 carban and 1 oxygen
These result from formation of hemiacital linkage b/w carbonyl and an alcohol group
TRIGLYCEROL
Triacylglycerols (formerly triglycerides) are the esters of glycerol with fatty acids. The fats and oils that are widely distributed in both plants and animals are chemically triacylglycerols.
They are insoluble in water and non-polar in character and commonly known as neutral fats.
Triacylglycerols are the most abundant dietary lipids. They are the form in which we store reduced carbon for energy. Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids. Most triacylglycerols are "mixed." The three fatty acids differ in chain length and number of double bonds
Structures of acylglycerols :
Monoacylglycerols, diacylglycerols and triacylglycerols, respectively consisting of one, two and three molecules of fatty acids esterified to
a molecule of glycerol
Lipases hydrolyze triacylglycerols, releasing one fatty acid at a time, producing diacylglycerols, and eventually glycerol
Glycerol arising from hydrolysis of triacylglycerols is converted to the Glycolysis intermediate dihydroxyacetone phosphate, by reactions catalyzed by:
(1) Glycerol Kinase
(2) Glycerol Phosphate Dehydrogenase
Free fatty acids, which in solution have detergent properties, are transported in the blood bound to albumin, a serum protein produced by the liver.
Several proteins have been identified that facilitate transport of long chain fatty acids into cells, including the plasma membrane protein CD36
Glycogen Storage Diseases are genetic enzyme deficiencies associated with excessive glycogen accumulation within cells.
- When an enzyme defect affects mainly glycogen storage in liver, a common symptom is hypoglycemia (low blood glucose), relating to impaired mobilization of glucose for release to the blood during fasting.
- When the defect is in muscle tissue, weakness and difficulty with exercise result from inability to increase glucose entry into Glycolysis during exercise.
Various type of Glycogen storage disease are
Type |
Name |
Enzyme Deficient |
I |
Von Geirke’s Disease |
Glucose -6-phosphate |
II |
Pompe’s Disease |
(1, 4)glucosidase |
III |
Cori’s Disease |
Debranching Enzymes |
IV |
Andersen’s Disease |
Branching Enzymes |
V |
McArdle’s Disease |
Muscles Glycogen Phosphorylase |