Introduction to Biochemistry

Assoc.Prof. Dr. Hasenan Nordin Dept. of Chemical Pathology USM Kubang Kerian Kelantan

Introduction
In human and other vertebrate animals, the specialized cell groups include a gastrointestinal system to digest and absorb food; a respiratory system to take up O2 and eliminate CO2; a urinary system to remove wastes; a cardiovascular system to distribute nutrients, O2 and the products of metabolism; a reproductive system to perpetuate the species; and nervous and endocrine systems to coordinate and integrate the functions of the other systems.
W.F Ganong

Cell
A cell is an intricate and complex structure where a lot of things constantly happen. For example, the cell structure needs to be constantly maintained, signals and materials need to be transferred in and out of the cell, energy must be harvested for use in e.g. physical and chemical work.

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To understand how a cell works, we need to understand how the different parts of the cell are constructed and how they interact with each other

The main sources of both materials and energy are carbohydrates, fat (lipids), and protein. These three classes of compounds, together with nucleic acids, are also the main components of a cell, After ingestion, compounds (food) are broken down into simpler constituents, and the energy released is transported and used for synthesis of cellular components and for other types (e.g. physical) of work.

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The basic structure, properties, and cellular functions of carbohydrates, lipids, proteins, and nucleic acids

Protein
Proteins are built up from amino acids which are linked by peptide bonds to form a polypeptide of defined sequence. Many proteins are folded into well defined globular shapes because the hydrophobic effect forces hydrophobic side chains along the polypeptide sequence to cluster together in a hydrophobic core.

Structure of protein
Primary (1) structure (the amino acid sequence),
Secondary (2) structure,

Tertiary (3, 3D) structure,

Quaternary (4) structure in the case of multi-chain proteins

Metabolism
Metabolism is the sum of all of the chemical transformations that occur in a cell or organism. Catabolism is the degradation phase of metabolism, in which organic nutrient molecules are converted to smaller products. In anabolism, also called biosynthesis, small molecules are used to make larger and more complex molecules. Anabolic reactions require the input of energy, generally in the form of the free energy of hydrolysis of ATP and the reducing power of NADH and NADPH.

Membrane transport
Ingested nutrients are digested and absorbed in the gastrointestinal tract and transported via the blood system to different organs for use as energy or as precursors for biosynthesis.
How is it possible for the molecules to be transported into cells when the lipid bilayer is almost impermeable for most ions and molecules?

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Accomplished by specific membrane proteins, called transporters. Only small uncharged molecules such as water, urea etc. can pass through the lipid bilayer by simple diffusion. Facilitated diffusion is transport of solutes through integral membrane proteins. This transport also occurs from higher to lower concentration without any need for energy input. Active transport is energy dependent and the transport is often connected to the hydrolysis of ATP as an energy source. Input of energy for transportation of solutes makes it possible to transport aqueous solutes against a concentration gradient.

Enzymes
Macromolecules, usually proteins, that can catalyze (speed up) particular chemical reactions, by binding the needed reactants (substrates) in an active sites that is specific to the reaction to be carried out

Cofactors
Essential ions and coenzymes. There are numerous coenzymes which participate in metabolism. NAD and NADP are the cofactors for large groups of dehydrogenases and reductases and participate in two-electron transfer reactions

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During the conversion of glucose to pyruvate via the glycolysis pathway, a total of 2 ATP and 2 NADH are gained. Kinases, dehydrogenases and isomerases are important enzymes in the pathway. Kinases transfer a phosphate group to or from ATP. They consist of at least two domains, one of which binds ATP and the other the substrate. Conformational changes play an important role in the catalysis carried out by these enzymes. Phosphofructokinase is particularly important in the control of glycolysis

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Many key enzymes in metabolism are allosterically regulated, often through feed-back inhibition. Phosphorylation of enzymes is a general way to regulate their activity.

Vitamins
Vitamins are small biomolecules that are needed in small amounts in the diet. Vitamins are classified in two major groups: water soluble and fat soluble. B-vitamins comprise a large group of vitamins which are involved in several different biochemical reactions. One example is the enzyme complex named pyruvate dehydrogenase where four different vitamins are involved in the conversion of pyruvate to acetyl CoA

Carbohydrates
There are three major classes of carbohydrates: 1) Monosaccharides, or simple sugars, consist of a single polyhydroxy aldehyde or ketone unit. 2) Oligosaccharides consist of short chains of monosaccharide units joined together with glycoside linkages. The most abundant oligosaccharides are the disaccharides, with two monosaccharide units. 3) Polysaccharides consist of long chains having hundreds or more of monosaccharides units.

Glycolysis
Metabolic pathway for the catabolic conversion of glucose to pyruvate with the formation of ATP.
The process is catalysed by ten cytosolic enzymes, and all of the intermediates are phosphorylated compounds. There is a net gain of two ATP and 2 NADH per oxidized glucose.

The citric acid cycle

The enzyme citrate synthase catalyses the condensation of acetyl CoA with oxaloacetate (a four carbon unit) to form citrate. Isocitrate is formed which is further oxidised to a-ketoglutarate by isocitrate dehydrogenase in a reaction that also yields CO2. a-ketoglutarate then undergoes dehydration and decarboxylation to succinylCoA and CO2. Succinyl-CoA reacts with GDP and Pi to form free succinate and GTP. Succinate is then oxidised to fumarate by succinate dehydrogenase which is further oxidsed to malate by NAD-linked malate dehydrogenase to regenerate a molecule of oxaloacetate.

Pentose phosphate pathway and fatty acid metabolism

Fatty acids form phospholipids and glycolipids (components of cell membranes), precursors of hormones and intracellular messengers, fuel molecules, etc.
Fatty acid synthesis requires C atoms (as acetyl CoA) and NADPH. Acetyl groups are translocated from mitochondria to the cytosol as citrate

Hormones
Hormones are chemical messengers synthesized by the body that initiate responses by high binding affinity and specificity to target cell receptors within the various organs in the body
Simply defined as a chemical messenger from one cell ( or a group of cells) to another

Function of hormones
Homeostasis Reproduction Growth and development Maintenance of internal environment Production, utilization and storage of energy

Types of Hormones
Water-soluble protein based hormone use secondary messenger Fat soluble - steroid hormones- able to enter cell

Water regulation
Body fluid homeostasis: stability in the osmolality of body fluids & volume of plasma. Mechanisms: intrinsic to body fluids & cardiovascular system Osmotic movement of water across cell membranes buffers ECF osmolality Osmotic movement of water across capillary membranes buffers acute changes in plasma volume Venous compliance Glomerular Filtration

Fluids and Electrolytes Imbalance

Common to all divisions in all departments and in all branches of medicine. Frequently encountered, frequently mismanaged. Difficult to treat. Needs monitoring and close follow up. Life threatening when severe.

Acid-Base Balance
The normal pH of systemic arterial blood is 7.35-7.45. pH is maintained by buffers. The important buffer systems include proteins, carbonic acid-bicarbonate buffers and phosphates. Homeostasis of pH is maintained by buffer systems, via exhalation of carbon dioxide, and via kidney excretion of H+ and reabsorption of HCO3- . The overall acid-base balance is maintained by controlling the H+ conc. Of body fluids, especially ECF.

Nucleic Acids
Composition: Made up of nucleotides which each consist of three parts - a sugar, a base, and a phosphate group (from H3PO4) Structure: polynucleotides which consist of bases attached to a backbone of sugar and phosphate groups

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Nucleic acids are polymers of nucleotides DNA and RNA: serve as the blueprints for proteins They ultimately control the life of a cell

DNA is double stranded: two polynucleotides twisted into a double helix Consists of four types of nucleotides Adenine pairs to Thymine Cytosine pairs with Guanine The sequence of nitrogenous bases carries genetic information

Base pair Nitrogenous base (A)

RNA
Usually single strands

Four types of nucleotides: A, C, G, and U

Unlike DNA, contains the base uracil in place of thymine Three types of RNA that are key players in protein formation:
messenger, transfer, and ribosomal

References
Basic Medical Biochemistry, A Clinical Approach; Dawn B Marks, Allan D Marks, Colleen M Smith Basic Concepts in Biochemistry; Hiram F Gilbert Review of Medical Physiology; William F. Ganong