Цифровая 3D-медицина

Ways of regulation of enzymatic activity

Enzymes phosphorylation/
dephosphorylation

The scheme of activation of pepsinogen – partial proteolysis

Dissociation of protein kinase A - Protein-protein interactions

Allosteric regulation

Regulation of the metabolic pathways
The key enzymes in the metabolic pathways usually catalyze:
► irreversible (→) or partially reversible reactions;
► the slowest reactions;
► reactions at the beginning of the metabolic pathways or in branching places of metabolic pathways.
Scheme of regulation of enzyme activity by feedback inhibition

Regulation of the metabolic pathways

Clinical applications of enzymes
► enzyme diagnostics;
enzymopathology:
accumulation of substrate reaction. For example, phenylalanine in phenylketonuria, free bilirubin in physiological jaundice of the newborn, some fats in diseases of lysosomal accumulation (lipidosis);
product deficiency. For example, melanin in albinism, catecholamines in parkinsonism;
both features simultaneously, as in glycogenosis, accompanied by hypoglycemia with an excess of glycogen in the liver;
► enzyme therapy;
► use of enzymes in medical technology and industry (Enzyme immunoassay: enzyme-antigen-antibody );
► use of enzyme inhibitors:
natural and artificial poisons
insecticides
herbicides
disinfectants such as triclosan
chemotherapy:
competitive inhibitors (Sulfonamides)
competition at the active site (treatment of methanol intoxication)
irreversible inhibition (nonsteroidal anti-inflammatory drugs –aspirin)
Anti-cancer drugs (Methotrexate – analogue of folic acid)

Principle serum enzymes
used in clinical diagnosis

Introduction to nucleic acids
Role of nucleotides:
-the energy currency in metabolic transactions (ATP, GTP),
-the essential chemical participants in signals transduction paths of hormones and other extracellular stimuli in the of cells
-the structural components of enzyme cofactors and metabolic intermediates
-the molecular repositories of genetic information.
Gene is a segment of a DNA molecule that contains the information required for the synthesis of a functional biological product, whether protein or RNA.
Ribosomal RNAs (rRNAs) are components of ribosomes
Messenger RNAs (mRNAs) are intermediaries, carrying genetic information from one or a few genes to a ribosome
Transfer RNAs (tRNAs) are adapter molecules that faithfully translate the information in mRNA into a specific sequence of amino acids.

Structure of nucleotides
nucleoside
nitrogenous (nitrogen-containing) base
N-β-glycosyl bond
phosphoric ester bond
β-furanose
(closed five-membered ring)

Major purine and pyrimidine bases of nucleic acids

Deoxyribonucleotides and ribonucleotides of nucleic acids
The nucleotide units of DNA (a) are usually symbolized as A, G, T, and C, sometimes as dA, dG, dT, and dC;
those of RNA (b) as A, G, U, and C..
In their free form the deoxyribonucleotides are commonly abbreviated dAMP, dGMP, dTMP, and dCMP;
the ribonucleotides, AMP, GMP, UMP, and CMP.

Some minor purine and pyrimidine bases

Some adenosine monophosphates
3,5-cyclic monophosphate (cAMP) guanosine 3,5-cyclic monophosphate (cGMP)

Phosphodiester linkages in the covalent backbone of DNA and RNA
The backbone of alternating pentose and phosphate groups in both types of nucleic acid is highly polar. The 5 end of the macromolecule lacks a nucleotide at the 5 position, and the 3 end lacks a nucleotide at the 3 position.
Some simpler representations of this pentadeoxyribonucleotide are:
pA-C-G-T-AOH, pApCpGpTpA, and pACGTA
5-phosphate group of one nucleotide unit is joined to the 3-hydroxyl group of the next nucleotide, creating a phosphodiester linkage
oligonucleotide