Thiamin: Vitamin B1

Thiamin, or vitamin B1, helps to release energy from foods, promotes normal appetite, and is important in maintaining proper nervous system function.

RDA (Required Daily allowance) Males: 1.2 mg/day; Females: 1.1 mg/day

Thiamin Deficiency

Symptoms of thiamin deficiency include: mental confusion, muscle weakness, wasting, water retention (edema), impaired growth, and the disease known as beriberi.

CLASSIFICATION OF ENZYMES

1. Oxidoreductases : Act on many chemical groupings to add or remove hydrogen atoms. e.g. Lactate dehydrogenase

2. Transferases Transfer functional groups between donor and acceptor molecules. Kinases are specialized transferases that regulate metabolism by transferring phosphate from ATP to other molecules. e.g. Aminotransferase.

3. Hydrolases Add water across a bond, hydrolyzing it. E.g. Acetyl choline esterase

4. Lyases Add water, ammonia or carbon dioxide across double bonds, or remove these elements to produce double bonds. e.g. Aldolase.

5. Isomerases Carry out many kinds of isomerization: L to D isomerizations, mutase reactions (shifts of chemical groups) and others. e.g. Triose phosphate isomerase

6. Ligases Catalyze reactions in which two chemical groups are joined (or ligated) with the use of energy from ATP. e.g. Acetyl CoA carboxylase

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.

Vitamin B12: Cobalamin

Vitamin B12, also known as cobalamin, aids in the building of genetic material, production of normal red blood cells, and maintenance of the nervous system.

RDA The Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4 mcg/day for adult males and females

Vitamin B12 Deficiency

Vitamin B12 deficiency most commonly affects strict vegetarians (those who eat no animal products), infants of vegan mothers, and the elderly. Symptoms of deficiency include anemia, fatigue, neurological disorders, and degeneration of nerves resulting in numbness and tingling.

Factors regulating blood calcium level

(i) Vitamin D

(a) Vitamin D and absorption of calcium: Active form of calcium is calcitriol. Calcitriol enters intestinal wall and binds to cytoplasmic receptor and then binds with DNA causes depression and consequent transcription of gene code for calbindin. Due to increased availability of calbindin, absorption of calcium increases leading to increased blood calcium level.
(b) Vitamin D and Bone: Vitamin D activates osteoblast, bone forming cells & also stimulates secretion of alkaline phosphatase. Due to this enzyme, calcium and phosphorus increase.

(c) Vitamin D and Kidney: Calcitriol increase reabsorption of calcium and phosphorus by renal tubules.

(ii) Parathyroid  hormone (PTH)

Normal PTH level in serum is 10-60ng/l.

(a) PTH and bones: In bone, PTH causes demineralization. It also causes recreation of collagenase from osteoclast  leads to loss of matrix and bone resorption. As a result, mucopolysacharides and hydroxyproline are excreted in urine.

(b) PTH and Kidney: In kidney, PTH causes increased reabsorption of calcium but decreases reabsorption of phosphorus from kidney tubules.

(iii) Calcitonin Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases osteoblasts.

Hyper Calcemia When plasma Ca2+ level is more than 11mg/dl is called Hypercalcemia. It is due to parathyroid adenoma or ectopic PTH secreting tumor. calcium excreted in urine decreases excretion of chloride causing hyperchloremic acidosis.

Hypocalcemia Plasma calcium level less than 8mg/dl is called hypocalcemia. Tetany due to accidental surgical removal of parathyroid glands or by autoimmune disease. In tetany, neuromuscular irritability is increased. Increased Q-7 internal in ECG is seen. Main manifestation is carpopedal spasm. Laryngismus and stridor are also observed.

Sugar derivatives

Sugar alcohol - lacks an aldehyde or ketone. An example is ribitol.

Sugar acid - the aldehyde at C1, or the hydroxyl on the terminal carbon, is oxidized to a carboxylic acid. Examples are gluconic acid and glucuronic acid

Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated.

N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH.

Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.

R-OH + HO-R'   → R-O-R' + H₂O

Disaccharides: Maltose, a cleavage product of starch, is a disaccharide with an α (1→4) glycosidic linkage between the C1 hydroxyl of one glucose and the C4 hydroxyl of a second glucose. Maltose is the α anomer, because the O at C1  points down from the ring.

Cellobiose, a product of cellulose breakdown, is the otherwise equivalent β anomer.  The configuration at the anomeric C1 is β (O points up from the ring). The β(1→4) glycosidic linkage is represented as a "zig-zag" line, but one glucose residue is actually flipped over relative to the other.

Other disaccharides

• Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose and fructose. Because the configuration at the anomeric carbon of glucose is α (O points down from the ring), the linkage is designated α (1→2). The full name is α -D-glucopyranosyl-(1→2) β -D- fructopyranose.
• Lactose, milk sugar, is composed of glucose and galactose with β (→4) linkage → the anomeric hydroxyl of galactose. Its full name is β -D-galactopyranosyl-(1→)- α -D-glucopyranose

Polysaccharides:

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects

Amylose is a glucose polymer with α (1→4) glycosidic linkages, as represented above. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end

Amylopectin is a glucose polymer with mainly α (1→4) linkages, but it also has branches formed by α (1→6) linkages. The branches are generally longer than shown above. The branches produce a compact structure, and provide multiple chain ends at which enzymatic cleavage of the polymer can occur. 

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α (1→6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose, with β (1→4) linkages. Every other glucose in cellulose is flipped over, due to the β linkages. This promotes intrachain and interchain hydrogen bonds, as well as van der Waals interactions, that cause cellulose chains to be straight and rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.

Glycosaminoglycans (mucopolysaccharides) are polymers of repeating disaccharides. Within the disaccharides, the sugars tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1→3) and β(1→4).

When covalently linked to specific core proteins, glycosaminoglycans form complexes called proteoglycans. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules. For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues.

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to a sulfated sugar called iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated

Heparin, a glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated.

Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling and adhesion at the cell surface have been identified that recognize and bind segments of heparan sulfate chains having particular patterns of sulfation

Lectins are glycoproteins that recognize and bind to specific oligosaccharides.

• Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools
• Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting phagocytosis of these organisms as part of the immune response.
• Selectins are integral proteins of the plasma membrane with lectin-like domains that protrude on the outer surface of mammalian cells. Selectins participate in cell-cell recognition and binding.