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.

Role of Coenzymes

The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another.

Ex. The hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD;

The amine (-NH2) carried by pyridoxal phosphate

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.

Enzyme Kinetics

Enzymes are protein catalysts that, like all catalysts, speed up the rate of a chemical reaction without being used up in the process. They achieve their effect by temporarily binding to the substrate and, in doing so, lowering the activation energy needed to convert it to a product.

The rate at which an enzyme works is influenced by several factors, e.g.,

• the concentration of substrate molecules (the more of them available, the quicker the enzyme molecules collide and bind with them). The concentration of substrate is designated [S] and is expressed in unit of molarity.
• the temperature. As the temperature rises, molecular motion - and hence collisions between enzyme and substrate - speed up. But as enzymes are proteins, there is an upper limit beyond which the enzyme becomes denatured and ineffective.
• the presence of inhibitors.
  • competitive inhibitors are molecules that bind to the same site as the substrate - preventing the substrate from binding as they do so - but are not changed by the enzyme.
  • noncompetitive inhibitors are molecules that bind to some other site on the enzyme reducing its catalytic power.
• pH. The conformation of a protein is influenced by pH and as enzyme activity is crucially dependent on its conformation, its activity is likewise affected.

The study of the rate at which an enzyme works is called enzyme kinetics.

Gluconeogenesis

It is the process by which Glucose or glycogen is formed from non carbohydrate substances.

Gluconeogenesis occurs mainly in liver.

Gluconeogenesis inputs:  
The source of pyruvate and oxaloacetate for gluconeogenesis during fasting or carbohydrate starvation is mainly amino acid catabolism. Some amino acids are catabolized to pyruvate, oxaloacetate, Muscle proteins may break down to supply amino acids. These are transported to liver where they are deaminated and converted to gluconeogenesis inputs. 
Glycerol, derived from hydrolysis of triacylglycerols in fat cells, is also a significant input to gluconeogenesis

Glycolysis & Gluconeogenesis pathways are both spontaneous If both pathways were simultaneously active within a cell it would constitute a "futile cycle" that would waste energy

Glycolysis yields 2~P bonds of ATP.
Gluconeogenesis expends 6~P  bonds of ATP and GTP.
A futile cycle consisting of both pathways would waste 4 P.bonds per cycle.To prevent this waste, Glycolysis and Gluconeogenesis pathways are reciprocally regulated.

Biotin

 Biotin helps release energy from carbohydrates and aids in the metabolism of fats, proteins and carbohydrates from food.

RDA The Adequate Intake (AI) for Biotin is 30 mcg/day for adult males and females

Biotin Deficiency Biotin deficiency is uncommon under normal circumstances, but symptoms include fatigue, loss of appetite, nausea, vomiting, depression, muscle pains, heart abnormalities and anemia.