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Current theory: Induced fit model: As the substrate binds to the enzyme, the shape of the enzyme site changes
to accommodate the reaction.
Fisher lock and key model: enzyme lock, substrate key
Chemical Nature of Enzymes: All known enzymes are proteins. They are high molecular weight compounds made up
principally of chains of amino acids linked together by peptide bonds.
Many enzymes require the presence of other compounds - cofactors - before their catalytic activity can be exerted.
This entire active complex is referred to as the holoenzyme; i.e., apoenzyme (protein portion) plus the cofactor
(coenzyme, prosthetic group or metal-ion-activator) is called the holoenzyme.
Apoenzyme + Cofactor = Holoenzyme
2. The structure of simple and complex enzymes. Cofactors, a difference between coenzyme and prostetic
group. The role of apoenzyme and coenzyme in enzymatic reactions?
Prosthetic vs Coenzymes
Prosthetic Group Coenzyme
Prosthetic group is a type of a helper molecule which is a Coenzyme is a specific kind of cofactor molecule which is
non proteinaceous compound that helps enzymes to an organic molecule that helps enzymes to catalyze
perform their functions. chemical reactions.
Bond with Enzymes
They bind tightly or covalently with enzymes to aid They bind loosely with the active site of the enzyme to
enzymes. help catalytic function.
Composition
Prosthetic groups are metal ions, vitamins, lipids, or Coenzymes are vitamins, vitamin derivatives or
sugars. nucleotides.
Main Function
Prosthetic group mainly provides a structural Coenzyme mainly provides a functional
Removal from the Enzyme
Prosthetic groups – covalently bound to active site Coenzymes can be easily removed from the enzymes.
cannot be easily removed from the enzymes.
Examples
Examples include flavin nucleotides and heme. Examples include AMP, ATP, coenzyme A, FAD, and NAD+,
S-adenosyl methionine
Enzymes:
Composed of proteins combined with non-protein structures (either organic or inorganic) that aid in their function:
Coenzymes
Cofactors – non protein part
Prosthetic groups e.g. Iron porphyryn complex for cytochrome
There are such three enzymes in pyruvate dehydrogenase complex: Pyruvate dehydrogenase, dihydrolipoyl acetyl
transferase, dihydrolipoyl dehydrogenase.
Enzymes are affected by changes in pH. The most favorable pH value - the point where the enzyme is most active - is
known as the optimum pH.
Extremely high or low pH values generally result in complete loss of activity for most enzymes. pH is also a factor in
the stability of enzymes. As with activity, for each enzyme there is also a region of pH optimal stability
Allosteric regulation:
Allosteric enzyme: a regulatory enzyme that has both an active site (for the substrate) and an allosteric site
(for the effector)
often catalyze the first step in a reaction pathway
If the effector is present, it binds to the allosteric site causing a conformational change to the active site
which then changes (increase or decreases) the enzyme activity
If no effector is present, the enzyme can still act on substrate (via the active site) to produce product
A form of feedback regulation in which an enzyme of a metabolic pathway is controlled by the end product of
that same pathway
Usually Participates in feedback regulation.
Does not display Michaelis Menton kinetics
Types of Active Site: Because enzymes, like all proteins, are made of amino acids, they can create active sites with a
wide variety of properties that can bind specifically to different substrates. Properties of amino acids which enzymes
can use to bind to substrates include:
Size and shape of active site – Can be created specifically to fit around a substrate.
Polarity or non-polarity – Polar molecules are attracted to other polar molecules, while non-polar molecules
prefer other non-polar molecules. In this way, parts of the active site can attract or repel different parts of
the substrate to create a better fit.
Positive or negative charge – When it comes to ions, opposites really do attract! Positive charges are
attracted to negative charges, and vice versa. Similar charges – two positive charges, for example – will
actively repel each other instead of attracting. This is another way in which an enzyme active site can attract
certain parts of substrates, while repelling others to create the right fit.
Hydrophobicity or hydrophilicity – Just like with polarity, in this case “like attracts like.” Hydrophobic amino
acids attract other hydrophobic molecules, and hydrophilic amino acids attract hydrophilic substrates.
Special properties of co-factors – Some vitamins and minerals are important because they are used as co-
factors that help enzymes bind to their substrates.
8. Biological functions of tricarboxylic acid cycle. NAD- and FAD- dependent reactions of Krebs cycle. Reaction of
substrate-level phosphorylation?
Oxidative Phosphorylation the use of oxygen to oxidise electron carriers NADHin order to generate ATP. ATP is made
via a mechanical reaction. Occurs during the electron transport chain
Macroergic bond is a high energy bond present in some phosphorus containing compounds in living organisms e.g.
Adenosine triphosphate and ADP. Compounds that contain these bonds are known as phophagen.
High-energy phosphate bonds are pyrophosphate bonds, acid anhydride linkages formed by taking phosphoric acid
derivatives and dehydrating them. As a consequence, the hydrolysis of these bonds is exergonic under physiological
conditions, releasing energy.
These reactions are, in general, not allowed to go uncontrolled in the human cell but are instead coupled to other
processes needing energy to drive them to completion. Thus, high-energy phosphate reactions can:
provide energy to cellular processes, allowing them to run
couple processes to a particular nucleoside, allowing for regulatory control of the process
drive a reaction out of equilibrium (drive it to the right) by promoting one direction of the reaction faster
than the equilibrium can relax.
ATP and energy coupling
Cells make endergonic reactions happen by supplying them with free energy released by exergonic reactions. Energy
coupling is the transfer of energy from one reaction to another in order to drive the second reaction
Example
10. Ways of ATP formation in the organism. What is tissue respiration? Structure and functions of respiratory
chain?
Tissue respiration: is the process by which food substances are broken down in living cells. A large amount of energy
is released for the cells to perform different activities. In tissue respiration, glucose combines with oxygen to release
energy, carbon dioxide and water
Overall: Glucose + Oxygen → CO2 + H2O + Energy
Substrate-level phosphorylation occurs in the cytoplasm of cells during glycolysis and in mitochondria during
the Krebs cycle under both aerobic and anaerobic conditions. In the pay-off phase of glycolysis, a net of 2 ATP
are produced by substrate-level phosphorylation. Substrate level phosphorylation is the synthesis of ATP by
direct transfer of phosphate group from a substrate (high energy intermediate) to a molecule of ADP (occurs
in glycolysis and the TCA cycle)
Oxidative Phosphorylation the use of oxygen to oxidise electron carriers NADHin order to generate ATP. ATP
is made via a mechanical reaction. Occurs during the electron transport chain
11. Classification and representatives of carbohydrates. Biological functions of carbohydrates in the organism?
Classification of carbohydrates:
Chemical Classification Physiological Classification
Monosaccharides: the simplest carbohydrates further Simple or Complex
classified: Simple: mono- and disaccharides (also known as
# of carbon atoms: Trioses, tetroses, pentose, “sugars”) and tri- and tetrasaccharides
hexoses, heptoses (oligosaccharides)
Functional Groups: Aldoses (aldehyde) or Complex: the polysaccharides
ketoses (ketone). Reducing sugars contains
aldehyde groups that are oxidised to
carboxylic acids e.g. glucose, fructose, lactose
Isomerism: D-Form (most common or L-form
Disaccharides: Glycosidic condensation of two Classified according to energy purposes i.e. available or not
monosaccharides available
Maltose: 2 glucose via maltase Available: as glucose, fructose, galactose between
Sucrose: glucose + fructose via sucrose monosaccharides, sucrose, lactose, maltose and
Lactose: glucose + galactose via lactase maltodextrin between oligosaccharides, and starch
Oligosaccharides: Glycosidic condensation of 2-10 and glycogen between polysaccharides;
monosaccharides Not Available: as xylose (monosaccharide),
Polysaccharides: Glycosidic condensation of >10 lactulose (see lactose) and raffinose (respectively di-
monosaccharides and trisaccharide), fiber (cellulose, hemicellulose,
Mostly used as storage molecules or cellular lignin, pectins etc.) and resistant or not digestible
structural component starch (polysaccharides
Can be linear or branched
Functions of polysaccharides:
1. Storage of polysaccharides:
Starch: A homopolymer of glucose linked by α-1, 4 glycosidic bonds. Contains unbranched helical amylose
and branched amylopectin
Glycogen: a homopolymer of glucose linked by α-1, 4 glycosidic bonds. Contains numerous branch points via
α-1, 6 glycosidic linkages
2. Structural polysaccharides:
Glycosaminoglycan’s (GAGs): heteropolymer chains containing repeating disaccharide units of an amino
sugar and an uronic acid. Major structural polysaccharides of extracellular matrix (ECM). Connective tissue
(CT) and outer cell membrane surfaces.
Proteoglycans: complex carbohydrates that have a central protein molecule to which many GAGs are
attached. 95% polysaccharides and 5% proteins. Located in ECM
Cellulose: major component of plants
3. Provide instant energy to the body: This appears to be the primary function of carbohydrates in the body.
4. Reserve food for the body emergency: The excess glucose in the body is converted to glycogen due to the
stimulation by the hormone insulin.
5. Carbohyrdrates form other bio molecules: Carbohydrates in excess are converted into other bio-molecules
of physiological importance like fats, by fatty acid synthesis reaction in the cell for storage in the body and
use in times of starvation.
6. Constitute genetic material: Carbohydrates form a part of genetic material like DNA and RNA in the form of
deoxyribose and ribose sugars. This as carbohydrates form heptulose sugars which are used to form ribose
sugars (pseudo-heptulose pathway)
7. Detoxification of the body by metabolism: Many drugs, toxic wastes in the body are metabolized for easy
excretion in the body. Some of these are water insoluble and hence they are difficult to be expelled in urine.
Body converts them into glucouronyl conjugates using the glucouronyl moiety derived from carbohydrates.
A carbohydrate moiety like glucose combines with uronic acid to form glucouronate. These conjugates of
insoluble substances with glucouronyls are more water-soluble and easily excreted from the body. Thus
detoxification of physiological importance is carried out to some extent with carbohydrate derivatives
Lipid Function
Cholesterol Structural component of membranes; precursor for bile acid and steroid synthesis
Fatty acids Energy source
Triglycerides Energy store
Phospholipids Structural components of membranes
Eicosanoids Multiple, including effect on blood coagulation, bronchial and vascular contractility,
reproduction
Sphingolipids CNS, Blood group substance
Classification of lipids
Essential Fatty acids:
Linolenic acid: Omega 3 fatty acid
Linoleic acids: Omega 6 fatty acid
Oleic acids: Omega 9 fatty acid
Arachidonic acids
Good Less than 200 40 or higher Less than 100 Less than 149
Synthesis of Cholesterol
Three stages of cholesterol biosynthesis
1. Synthesis of isopentenyl pyrophosphate, that is the key building block of cholesterol, from acetyl CoA
2. Condensation of six molecules of isopentenyl pyrophosphate to form squalene
3. Squalene cyclizes and the tetracyclic product is converted into cholesterol
Transport of cholesterol in blood
Cholesterol travels in the blood transported in molecules called lipoproteins. These are sphere shaped assemblies
(containing lipids and proteins) that keep the cholesterol separated from the blood due to the soluble nature of the
assemblies.
LDL is the major carrier of cholesterol in the blood taking it to peripheral tissues. It is taken up by cell mediated
endocytosis. Cells of all organs have LDL receptors. Receptors for LDL are localized in specialized regions called coated
pits, which contain a specialized protein called clathrin Apo B-100 on the surface of an LDL binds to the receptor
Receptor-LDL complex enters the cell by endocytosis. Endocytic vesicle is formed. Vesicle fuse with lysosomes
Lysosomal lipases and proteases degrade LDL LDL receptor itself returns to the plasma membrane Apo B-100 is
hydrolyzed to amino acids Cholesteryl esters are hydrolyzed to free cholesterol and fatty acids
Feedback regulation:
Abundance of intracellular cholesterol suppresses the synthesis of LDL receptors and so the uptake of additional
cholesterol from plasma LDL is blocked
Lipid Transport
Lipoproteins
Transport lipids in blood plasma
Composed of a non-polar core surrounded by a single layer of amphipathic phospholipids and cholesterol
Characterized by the protein moiety embedded in their outer layer (apoprotein)
Contain triglycerides 156%, phospholipids (30%) cholesterol (14%) cholesterol esters (36%) and free fatty
acids 4%
Filmilial Hypercholesterolemia is caused by an autosomal dominant defect of the low density lipoprotein (LDL)
receptor, leading to increased plasma LDL cholesterol and atherosclerosis
The desirable level of cholesterol in blood plasma: < 200 mg/dl (< 5 mmol/l)
For a healthy person, the LDL/HDL ratio is 3.5
17. Pathologies of lipids metabolism?
18. Biological role of proteins in the organism. Nitrogenous balance. Protein standards in nutrition. Essential and
nonessential amino acids?
19. Transamination and decarboxilation of amino acids, mechanism, role of enzymes and coenzymes?
Oxidative deamination
L-Glutamate dehydrogenase plays a central role in amino acid deamination
In most organisms glutamate is the only amino acid that has active dehydrogenase
Transamination: transfer of an amino group from an alpha amino acid to an alpha keto acid (usually to
Alpha ketoglutarate)
Enzymes: aminotransferases (transaminases).
Aminotransferases funnel α-amino groups from a variety of amino acids to α-ketoglutarate with glutamate formation
Glutamate can be deaminated with NH4 + release
Mechanism of transamination
All aminotransferases require the prosthetic group pyridoxal phosphate (PLP), which is derived from pyridoxine
(vitamin B6).
Ping-pong kinetic mechanism
First step: the amino group of amino acid is transferred to pyridoxal phosphate, forming pyridoxamine
phosphate and releasing ketoacid.
Second step: α-ketoglutarate reacts with pyridoxamine phosphate forming glutamate
Decarboxylation: removal of carbon dioxide from amino acid with formation of amines. Usually amines have high
physiological activity (hormones, neurotransmitters etc).
Enzyme: decarboxylases
Coenzyme: pyrydoxalphosphate
2. Catabolism of amino acids during the decay of proteins: Enzymes of microorganisms (in colon; dead organisms)
decarboxylate amino acids with the formation of diamines.
Inactivation of hormones
After biochemical effect hormones are released and metabolized. Hormones are inactivated mainly in liver
Inactive metabolites are excreted mainly with urine
Half-time life
from several min to 20 min – for the majority of hormones
till 1 h – for steroid hormones
till 1 week – for thyroid hormones
21. Hormones of anterior pituitary (7 hormones). Why these hormones are called “tropic” hormones?
Hormone Released Chemical Class Target tissues/ organs Chief function of hormones
Thyroid Stimulating Glycoprotein Thyroid Stimulates thyroid to release T3 and T4
hormone TSH
Adrenocorticotropic ACTH Peptide Adrenal cortex Stimulates adrenal cortex -Secretion of
(Cushing disease hyper glucocorticoid, mineralocorticoid and
secretion of ACTH) androgens
Follicle stimulating Glycoproteins Gonads Sex hormone production
hormone
Prolactin PRL Protein Mammary gland Milk production
Growth hormone GH Simple Protein Soft tissue, bones Cell division, protein synthesis and bone
(hyper secretion leads to growth
gigantism)
Melanocyte stimulating Peptide Melanocytes in skin Regulate skin color
hormone MSH
Luteinizing Hormone Glycoprotein Gonads Sex hormone production
They are called tropic hormones as they stimulates somatic growth of organs and tissues, particularly bones,
cartilages, muscles
22. Somatotropic hormone: structure, effect on protein, carbohydrate and lipid metabolism. Clinical
manifestations of the changing of somatotropic hormone concentration in children and adults?
In the inherited hypoplasia of pituitary gland dwarfism is developed. For the treatment GH is used.
Hyper production of GH before puberty and before the completion of ossification results in gigantism
Hyper function of pituitary in adults results in acromegaly: un-proportionally intensive growth of particular body
parts (fingers, nose, lower jaw, tongue, inner organs). Cause: tumor of anterior pituitary
23. Thyrotropic, adrenocorticotropic and follicle stimulating hormone: chemical structure, biological role?
Gonadotropic hormones
Follicle-stimulating
Chemical nature: protein (glycoprotein)
Secretion is stimulated by foliliberin
Function: stimulates the function of follicles in women and spermatogenesis in men
Luteinizing hormone
Chemical nature: protein (glycoprotein)
Secretion is stimulated by luliberin
Function: stimulates the follicular growth and conversion of the follicle into a corpus luteum in women and secretion
of testosterone in men
25. Iodine containing hormones of thyroid gland. Effect of these hormones on protein, carbohydrate, lipid
metabolism?
Hormone Released Chemical Class Target tissues/ organs Chief function of hormones
Thyroxine T4 and Iodinated amino All tissues Increases metabolic rate, regulates
triiodothyronine T3 acids – derivatives of growth and development
– hypersecretion amino acids
results in Goiter,
Hypo secretion –
cretinism/
myoxedema (in
adults)
Calcitonin Peptide Bones, kidneys, intestines Raises blood calcium and phosphate
(Hypersecretion level
Hypocalciemia,
hypophosphatemia,
hyperphosphaturia)
Hormone Cells involved Chemical Target tissues/ organs Chief function of hormones
Released Class
Insulin Beta cells of Protein Liver, muscle, adipose Lowers blood glucose level, by
Langerhans tissue, myocytes and glucose phosphorylation oppression
adipocytes
promotes formation of glycogen
Activates oxidization of glucose in
glycolysis, activates a PPP, activates
glycogen synthase (synthesis of
glycogen)
Activates synthesis of fats, represses
a gluconeogenesis
27. Insulin: chemical structure, proinsulin, regulation of insulin production, target tissue for insulin. Effect of
insulin on carbohydrate, lipid, protein metabolism?
Effect of Insulin
Carbohydrate Protein Lipid
Activates glucokinase (hexokinase) Increases the permeability of Activates of the lipids synthesis
phоsphоfructokinase, pyruvatkinase membranes for AA Activates the synthesis of fatty acids
in glycolysis
Activates TAC (citrate synthase Activates synthesis of proteins and Promotes the saving of fats activating
nucleic acids the decomposition of carbohydrates
Activates PPC (G-6-PDH) Inhibits gluconeogenesis Inhibits gluconeogenesis
Activates glycogen synthase It depresses mobilization of fat from
a depot
Activates pyruvate- and alpha-
ketoglutarate dehydrogenase
Inhibits gluconeogenesis
Inhibits the decomposition of
glycogen (glucose-6-phosphatase)
Activates transfer of glucose through
the cells membranes
Endocrine Hormone Released Chemical Target tissues/ organs Chief function of hormones
Gland Class
Testes Androgens – Steroid Gonads, skin, muscle and Stimulates male sex characteristics
Testosterone bones
Ovaries Estrogen and Steroid Gonads, skin, muscle and Stimulates female sex characteristics
progesterone bones
Estrogens
Nature: steroids
Estradiol – is formed in follicles of ovarium
Estron and estriol – are formed in liver and placenta in the metabolism of estradiol
Functions of estrogens
Development of the female reproductive system organs
Ability to fertility in reproductive period
Biochemical functions of estrogens
Anabolic action on the tissues of reproductive organs
Inhibit the exit of Ca from bones (osteoporosis in menopause)
Progesterone
Nature: steroid
Is formed in corpus luteum, placenta and epinephrine glands
Functions of progesterone
Prepares the endometrium of uterus to implantation of ovum
Inhibits the uterus contraction during pregnancy
Stimulates the growth of mammary glands
Androgens
Testosterone
Nature: steroid
Is formed in the interstitial cells of testis, Is excreted as 17-кetosteroids
Functions of testosterone
Development of the primary sex features
Development of the secondary sex features
Stimulates spermatogenesis
Biochemical functions of testosterone
Strong anabolic action (stimulates the synthesis of NA, proteins, phospholipids), increases the mass of
muscles
Keeps the Ca and P in organism
Glucocorticoids
Most important: corticosteron, cortison, hydrocortison
Synthesis is regulated by ACTH
Are transported combined with proteins
Half-life time: up to 1 hour
In the decomposition17-ketosteroids are formed (excretion with urine). Diagnostic significance – index of the
function of cortex of epinephrine glands and testis
Functions
Anti-inflammatory, ant allergic, autoimmune
Adaptive effect
Maintain the blood pressure
Maintain the volume of extracellular liquid
Carbohydrate Protein Lipid
Increase the glucose level: Stimulate catabolic processes in Activate lipolysis
• Activate gluconeogenesis connective, lymphoid and muscle
• Inhibit hexokinase (glycolysis) tissues
Activate protein synthesis in liver Activate the conversion of FA into
carbs
Stimulate amino transferases
Stimulate the urine biosynthesis
30. Concepts "vitamin" and "provitamin".Classification of vitamins. Chemical and physiological name,
coenzymes, biological role of vitamins B1. Manifestations of hypovitaminosis, nature sources and day
requirement of vitamins B1?
Vitamin B1 – thymine antineurotic, consists of 2 rings a pyrimidine and a thiazole. Vitamin B1 is phosphorylated in
the liver to TMP, TPP – thiamine pyro phosphate (involved in oxidative decarboxylation), Thiamine diphosphate and
TTP who are coenzymes of pyruvate and alpha ketoglutarate dehydrogenase and transketolase.
Pro-vitamin is a substance that may be converted within the body to a vitamin. E.g. "Provitamin B5" is a name for
panthenol, which may be converted in the body to vitamin B5 (pantothenic acid), pro-vitamin A" is a name for β-
carotene which has only about 1/6 the biological activity of retinol (vitamin A); the body uses an enzyme to convert
β-carotene to retinol
Cofactors are molecules that attach to an enzyme during chemical reactions. In general, all compounds that help
enzymes are called cofactors. However, cofactors can be broken down into three subgroups based on chemical
makeup and function:
Coenzymes: These are reusable non-protein molecules that contain carbon (organic). They bind loosely to an enzyme
at the active site to help catalyze reactions. Most are vitamins, vitamin derivatives, or form from nucleotides. They
typically are produced from vitamins such as B vitamins. examples of coenzymes are NAD (derived from Vitamin B 3)
and Coenzyme A (derived from Vitamin B5), FMN and FAD
Cofactors: Unlike coenzymes, true cofactors are reusable non-protein molecules that do not contain carbon
(inorganic). Usually, cofactors are metal ions such as iron, zinc, cobalt, and copper that loosely bind to an enzyme’s
active site. They must also be supplemented in the diet as most organisms do not naturally synthesize metal ions.
Prosthetic groups: These can be organic vitamins, sugars, lipids, or inorganic metal ions. However, unlike coenzymes
or cofactors, these groups bind very tightly or covalently to an enzyme to aid in catalyzing reactions. These groups are
often used in cellular respiration and photosynthesis.
reddening of oral mucosa, cracks on the lips and mouth corners, face skin dryness and desquamation,
conjunctiva inflammation, vasculature invasion into the cornea
Sources: Cereals, nuts, milk, eggs, green leafy vegetables and meat
32. Chemical and physiological name, coenzymes, biological role of vitamin B5. Manifestations of
hypovitaminosis, nature sources and day requirement of vitamin B5?
Hypovitaminosis:
dermatitis
ulcers of mucosa
spasms, paresis
hypo-lipidemia
liver steatosis
absence of appetite, nausea, pain of stomach, diarrhea, head ache, disorders of memory
33. Chemical and physiological name, coenzymes, biological role of vitamin B3. Manifestations of
hypovitaminosis, nature sources and day requirement of vitamin B3?
Vitamin В3 (РР, nicotinic acid, nicotinamide niacin, anti-pellagric)
34. Chemical and physiological name, coenzymes, biological role of vitamin B6. Manifestations of
hypovitaminosis, nature sources and day requirement of vitamin B6?
Vitamin В6 (pyridoxine, аnti-dermatitic)
Form coenzymes: pyridoxal phosphate carries chemical groups only (PLP), pyridoxamine and monophosphate (PMP)
Symptoms of hypovitaminosis:
hyperaminoaciduria
negative nitrogen balance
dermatitis (erythema, pigmentation, edema)
anemia (disorders of iron utilization)
leucopenia (disorders of protein synthesis)
growth inhibition
convulsions, muscle spasms (GABA inhibition)
35. Chemical and physiological name, coenzymes, biological role of vitamin B10. Manifestations of
hypovitaminosis, nature sources and day requirement of vitamin B10?
Biological role of THFA: transfers methyl groups in the synthesis of amino acids, pyrimidine nucleotides, creatin and
methionine. In deficiency – disorders of the NA and protein synthesis, inhibition of growth and cell division
Symptoms:
hyper chromic megaloblastic anemia treatment in combination of folic acid and Vitamin B12
leucopenia
thrombocytopenia
glossitis, conjunctivitis, gastritis (disorders of epithelium proliferation)
growth inhibition
impairment of the wound healing
immunodeficiency
36. Chemical and physiological name, coenzymes, biological role of vitamin B12. Manifestations of
hypovitaminosis, nature sources and day requirement of vitamin B12?
Symptoms of avitaminosis:
hyper chromic megaloblastic anemia (malignant, pernicious, Addison-Birmer disease)
fatty dystrophy of nervous cells, neurological disorders
cardiovascular disorders (accumulation of homocysteine)
Avitaminosis: can be caused by stomach resection – castle factor
Food source of vitamin B12: egg, meat, poultry and diary, Liver
Use Methylmalonic acid for diagnosis of vitamin B12
Is not synthesized neither in plants nor in animals. Is formed only by intestinal bacteria. It is absorbed in small
intestine
37. Chemical name, biological role of vitamin H. Manifestations of hypovitaminosis, nature sources and day
requirement of vitamin H?
Vitamin Н or B7 (biotin, anti-seborrheic)
Structure: consists of imidazole and thiophenone rings and Valerian acid
Coenzyme of carboxylase: serves as transporter of carboxylic group
Pyruvate carboxylase in gluconeogenesis
Acetyl-СоА carboxylase, propionyl-СоА carboxylase in lipid metabolism
Biotin can bind CO2 and transport it
Hypovitaminosis almost does not occur can be in malabsorption, dis-bacteriosis, using of large amount of eggs white
which contains avidin (glycoprotein that irreversibly binds biotin – аnti-vitamin)
Symptoms of hypovitaminosis:
seborrheic dermatitis of the hair part of head
conjunctivitis
anemia
depression
Daily requirement: 150-200 mg
Food: liver, soybeans, egg yolks, mushrooms, beans, onion, spinach
38. Chemical name, structure, active forms and properties of vitamins C. Biological role of vitamins C.
Manifestations of vitamins C hypovitaminosis. Nature sources and day requirement of vitamins C. Clinical
symptoms of vitamin P hypovitaminosis?
Vitamin C has oxidation-reduction properties, can donate hydrogen, as result is converted to dehydroascorbic acid
Biological role of vitamin C:
reduces sulfhydryl groups of proteins, enzymes
formation of serotonin
synthesis of norepinephrine
synthesis of steroid hormones
formation of carnitine
synthesis of collagen (hydroxyl proline) – hydroxylation pf proline
formation of THFA
decomposition of hemoglobin
Fe3+ ® Fe2+ - absorption in the intestine
promote immunity defense
required for synthesis of bile acids, collagen, epinephrine, intestinal absorption of iron
Daily requirement: 80-100mg or 75-100 mg, Requirement is increased in infections, flue, in pregnancy
Food: Citrus fruit,
39. Common properties of fat soluble vitamins. The differences of fat soluble vitamins from water soluble
vitamins?
40. Chemical and physiological name, structure and provitamins of vitamin A. Biological role of vitamins A.
Clinical symptoms of vitamin A hypovitaminosis and hypervitaminosis. Nature sources and day requirement
of vitamins A?
Precursors/Provitamin: carotenoids most important is Beta carotene which is cleaved to retinol in the liver
Hypovitaminosis Hypervitaminosis
Night blindness- prolonged dark adaptation time Accumulates in liver
Anemia (vit. A is required for the synthesis of vomiting, diarrhea
transferrin)
Increased susceptibility to infection and cancer liver and spleen enlargement
Follicular hyperkeratosis (“goosebumps” skin)
Xerophthalmia (progressive keratinization of cornea) loss of hair
Keratomalacia (corneal ulcerations) dermatitis
pyelonephritis (change of endothelium in nephrons)
Twilight vision impairment
41. Chemical and physiological name, structure and provitamins of vitamin D. Biological role of vitamins D.
Clinical symptoms of vitamin D hypovitaminosis. Nature sources and day requirement of vitamin D and
hypervitaminosis?
Vitamin D: (cholecalciferol, аntirickets)
Two forms of vitamin D: Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol), both of them are metabolized
by the liver
Parathyroid hormone stimulates the formation of 1,25- dihydroxycholecalciferol in kidneys
Pro vitamin of D3 is 7-dehydrocholesterol
Active form is Calcitriol (1,25- dihydroxycholecalciferol)
Deficiency: rickets and osteomalacia
Functions of vitamin D:
regulates the Ca and P levels in the blood and it acts in concert with parathyroid hormone
promotes absorption of Ca and P in the intestine
promotes reabsorption of Ca in the kidneys
high levels of serum Ca and P increase the rate of bone mineralization
promote bone resorption (at low Ca in blood)
promotes phagocytosis
immunomodulatory activity
induces differentiation of immune cells
stimulates the formation of 1,25- dihydroxycholecalciferol in kidneys
dysfunctional parathyroid leads to spasm development
prevents tumor genesis
o inhibits proliferation
o inhibits angiogenesis
o induces differentiation
Activates reabsorption of amino acids, especially proline
Activates the monosaccharides phosphorylation (glycogen synthesis)
Promotes ATP formation
Causes: Hypercalciemia, hypophosphatemia and the intensive excretion of phosphorus with urine
Hypocalciemia, hyperphosphatemia and decreased excretion of phosphorus with urine were found. It can be
caused by: Decreased production of parathormone
Hypo-vitaminosis Hyper-vitaminosis
Increase of Ca and P in blood
Richkets: softening of bone symptoms include: muscle Demineralization of bones
weakness, Tetany, deformed skeletal bones i.e. bowed Calcification of inner organs
legs, Dental problems, fractures and hypocalcemia Renal stones
42. Chemical and physiological name, biological role of vitamin E. Clinical symptoms of vitamin E
hypovitaminosis. Nature sources and day requirement of vitamin E and hypervitaminosis?
Hypovitaminosis of vitamin E is caused by: malabsorption and famine and symptoms include:
Activation of FRO
Increase of membrane permeability
Hemolysis of erythrocytes
Deficit of ATP
Muscle dystrophy (creatinuria)
Demyelization of nerves (CNS changes)
Disorders of reproductive function (atrophy of testis, azoospermia, inability to implantation)
43. Chemical and physiological name, biological role of vitamin K. Clinical symptoms of vitamin K hypovitaminosis
and hypervitaminosis. Nature sources and day requirement of vitamin K. Chemical and physiological name,
biological role of vitamin F. Nature sources and day requirement of vitamin F.
Hypovitaminosis of vitamin K
Causes by:
Lipids malabsorption (lack of bile acids)
Disbacteriosis (vitamin K is synthesized by intestinal microflora)
Taking of antivitamins (dicumarol)
Lack of red meat does not cause vitamin K deficiency
Symptoms:
Hemorrhages (subcutaneous, intramuscular, into inner organs)
Increased coagulation time
Hypovitaminosis of vitamin F
Causes/ symptoms:
Growth retardation
Dermatitis
Dry skin
Eczema
Atherosclerosis
Daily requirement: 10-15g
44. The blood functions, their characteristic. Biochemistry of blood cells. Function of leucocytes?
Functions of blood
1.Transport:
transport of oxygen and carbon dioxide
transport of nutrients and products ofmetabolism
2. Osmotic.
3. Regulatory (formation of hormonoids).
4. Protective.
5. Detoxification.
6. Thermoregulatory.
Leukocytes
45. Respiratory function of erythrocytes. Structure and biological role of hemoglobin. Types of hemoglobin?
Erythrocyte functions: erythrocytes are dedicated to respiratory gas transport. Hemoglobin reversibly binds with
oxygen and most oxygen in the blood is bound to hemoglobin. Erythrocytes do not contain nucleus and mitochondria
Main protein – hemoglobin (35 %) Energy – from glycolysis Life span – 120 days Formation is stimulated by
erythropoetin
Normal level of hemoglobin (Hb) in blood in males is 14–16 g/dl and in females, 13–15 g/dl.
Hb is globular in shape
STRUCTURE OF HEMOGLOBIN
Hemoglobin is a porphyrin containing compound, it’s a tetramer made up of 4 subunits where each subunit is
contains a heme group (prosthetic group) and a polypeptide chain. It has tertiary protein structure. The 4
polypeptide chains are held by disulfide bridges
46. Structure and biological role of hemoglobin. Types of hemoglobin. Pathological hemoglobin’s. Derivatives of
hemoglobin, conditions of their appearance?
Hemoglobin Derivatives:
Oxyhemoglobin oxy-Hb bright red substance formed by the combination of haemoglobin with oxygen,
present in oxygenated blood.
Deoxyhemoglobin Deoxy-Hb Hb without oxygen
Methemoglobin Met-Hb Fe3+ instead of Fe2+ in heme group, can be due to congenital disease, drugs such as
benzocaine, aniline dyes
Carbonyl hemoglobin HbCO CO binds to Fe2+ in heme in the case of CO poisoning. CO has X200 the affinity to Fe 2+
than oxygen
Carbaminohemoglobin CO2 is non covalently bound to globin chain of hemoglobin
HbCO2
Hemichromes Hemichromes are typically produced by the slow denaturation of methemoglobin
Ferritin High levels of ferritin can indicate an iron storage disorder, such as hemochromatosis,
or a chronic disease process. Low levels of ferritin are indicative of iron deficiency,
which causes anemia
Hemosidirin a yellowish brown granular pigment formed by breakdown of hemoglobin, found in
phagocytes and in tissues especially in disturbances of iron metabolism (as in
hemochromatosis, hemosiderosis, or some anemias)
Thalassemias are inherited blood disorders characterized by abnormal hemoglobin production. The thalassemias are
classified according to which chain of the hemoglobin molecule is affected. In α-thalassemias, production of the α
globin chain is affected, while in β-thalassemia, production of the β globin chain is affected.
α-thalassemias involve the genes HBA1[26] and HBA2,[27] inherited in a Mendelian recessive fashion
Beta thalassemias are due to mutations in the HBB gene on chromosome 11,[28] also inherited in an
autosomal, recessive fashion.
Delta-thalassemia
Hemoglobin E or haemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the β chain
Hemoglobin c (abbreviated as Hb C or HbC) is an abnormal hemoglobin in which substitution of a glutamic acid
residue with a lysine residue at the 6th position of the β-globin chain has occurred
Hemoglobin D caused by substitution of glutamine instead of glutamate
Hemoglobin S (Hgb S) is an abnormal type of hemoglobin that you can inherit from your parents. Hgb S causes red
blood cells to become stiff and abnormally shaped. Instead of having a normal round, disk shape, these red blood
cells become sickle-shaped,
47. The total contents of proteins in blood plasma.The main proteins of blood plasma. Causes and consequences
of hyperproteinemia and hypoproteinemia?
Possible causes of high blood protein include I.e. hyperproteinemia:
Amyloidosis (buildup of abnormal proteins in your organs)
Dehydration.
Hepatitis B.
Hepatitis C.
HIV/AIDS.
Monoclonal gammopathy of undetermined significance (MGUS)
Multiple myeloma.
Causes of hypoproteinemia:
Celiac disease
Poor diet (not enough calories) – not enough protein consumption
Liver disorder
Kidney problems i.e. pissing away proteins
Inflammatory bowel disease
48. Albumins: content in blood plasma, physical and chemical properties.Functions of albumins?
Serum albumin concentration is typically 35 - 50 g/L (60% of plasma content)
Functions of albumin:
Maintains oncotic pressure
Transports thyroid hormones
Transports other hormones, in particular, ones that are fat-soluble
Transports fatty acids ("free" fatty acids) to the liver and to myocytes for utilization of energy
Transports unconjugated bilirubin
Transports many drugs; serum albumin levels can affect the half-life of drugs
Competitively binds calcium ions (Ca2+)
Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is
not a valid marker of nutritional status; rather, it is a marker of an inflammatory state
Prevents photodegradation of folic acid
49. Globulins: content in blood plasma, physical and chemical properties.Functions of globulins?
Globulins are produced by liver and by plasma cells, which develop from B lymphocytes. Antibodies
(immunoglobulins- glycoproteins)) help attack viruses and bacteria. Alpha and beta globulins transport iron, lipids,
and fat-soluble vitamins.
Alpha 1 Globulin: antitrypsin, alpha lipoproteins
Alpha 2 globulins: Caeruloplasminn (copper carrying protein in blood, deficiency leads to Wilson disease),
heptoglobins (acute-phase reactant whose principal clinical utility is in defining conditions of hemolysis.
levels can also become elevated in infection and inflammation), alpha 2 macroglobulin
Beta globulins: beta lipoproteins, transferrin (Transferrins are iron-binding blood plasma glycoproteins that
control the level of free iron), fibrinogen
Gamma globulins: immunoglobulins, CRP
E and D globulins: not synthesized in liver
50. LDL and HDL as the principal transport forms of cholesterol.The direction of the cholesterol transport by LDL
and HDL. The principle of percentage ratio determination of LDL and HDL in blood serum, usage of this index
in atherosclerosis pathogenesis.
glycolisis
metabolism of fructose and galactose
gluconeogenesis (from amino acids and glycerine)
release of glucose into blood (maintain the stable glucose concentration in blood)
conversion of pyruvate into acetyl CoA
tricarboxylic acid cycle
pentose phosphate pathway NADPH2/ NADPH and pentose synthesis)
glycogenolysis, glycogenogenesis
Synthesis of lipoproteins
Synthesis of triacylglycerol’s
Synthesis of phospholipids
Synthesis of fatty acids, elongation of fatty acids chain, desaturation
Synthesis of cholesterol
Ketone bodies formation (from acetyl CoA in mitochondria of livercatalse)
Lipolysis
Fatty acids oxidation
55. Liver’s functions. Role of liver in regulation of vitamin metabolism and water-salts balance?
Vitamin Metabolism:
Formation of active form of vitamin D
Formation of vitamin A from carotenes
Depo of cyanocobalamin (synthetic form of vitamin B12) and folic acid
Depo of vitamin E
Phosphorylation of vitamins B, formation of coenzyme forms
Albumin helps in maintaining osmolarity and liver also produces Angiotensin which is involved in water salt balance
of the body i.e. Renin, Angiotensin, Aldosterone system, lack of albumin leads to edema/edemata
56. Liver’s functions. Role of liver in secretion of bile. The decomposition of hemoglobin in tissues, bile pigments
formation.
Main functions of liver:
1. Metabolism: anabolism and catabolism
2. Storage of nutrients: carbohydrates and fats can be stored as glycogen (polysaccharide), lipoprotein or as
triglycerides. Proteins are not stored in liver but are processed into molecules like albumin and are released
into the blood stream
3. Detoxification: modifying toxins so they can’t hurt our body. This is achieved mainly by Cytochrome P450
enzymes (induces conjugation via inductor of the synthesis of UDP-glucuronyltransferase, contains Feci)
4. Bile Production: bile is needed for absorption of fats from our foods.
5. Depot of iron and vitamins
Bile: bile is a digestive juice that is produced in the liver and stored in the gall bladder. Composition of bile in the gall
bladder is 97% water, 0.7% bile salts/acids which are amphiphilic steroids that emulsify ingested fats e.g. cholic acid,
DeoxyCholic acid and Tauracholic acid, 0.2% Bile pigments i.e. break down products of hemoglobin e.g. bilirubin,
0.5% fats (cholesterol, fatty acids and lecithin)
Bile pigment formation i.e. bilirubin: Red blood cells have a life span of roughly 120 days and then gets destroyed in
the spleen and the liver by macrophages. This releases the hemoglobin component which is then split into the heme
and globin component. The globin is further split into amino acids and recycled in the body. The heme is then split
into iron and Biliverdin. The Biliverdin is then converted into unconjugated bilirubin (non-water soluble) by the
enzyme Biliverdin Ruductase. The conjugated Bilirubin is transported to the liver with albumin as a carrier protein
where it is converted to conjugated Bilirubin (i.e. water soluble form). This is achieved with the combination of
Glucuronic acid with unconjugated Bilirubin.
The conjugated Bilirubin is then transported through the biliary channels to the duodenum. In the colon the bilirubin
is converted to urobilinogen and stercobilinogen and these are secreted as Stercobilin.
Classification of Jaundice
Class of Jaundice Types of Bilirubin increase Causes
Pre-hepatic or Unconjugated / indirect Abnormal red blood cells; antibodies; drugs and toxins;
hemolytic thalassemia; hemoglobinopathies, deficiency of UDP-
glucuronyltransferase, immune hemolytic anemia
Hepatic or Unconjugated and Viral hepatitis, toxic hepatitis, intrahepatic cholestasis
hepatocellular conjugated
Post-hepatic/ Conjugated/direct or and Gallstones (made from cholesterol), tumors of bile duct or
Mechanical / unconjugated/ indirect pancreas
obstructive
Liver function can be tested with measurement of bilirubin in serum and urobilinogen in urine.
Normal serum bilirubin: 0.2-0.6mg/dl
Normal Conjugated bilirubin: 0-0.2mg/dl
A rise in serum bilirubin above 1 mg/dl is abnormal (latent jaundice) but jaundice only appear if level is
above 2mg/dl
59. Physical and chemical characteristics and components of urine: a) volume, physical and chemical properties
of urine; b) inorganic components of urine; c) organic components of urine?
Properties of urine:
1. Amount: 1500-2000mL/day
1. Polyuria: caused by diabetes mellitus (high osmotic pressure of urine) and insipidus (insufficient
ADH)
2. Oliguria: heart failure, nephritis, vomiting , fever
3. Anuria: due to kidney failure, acute intoxication by heavy metals
2. Color: straw-yellow
1. if pale then its Polyuria (diabetes insipidus)
2. if dark then its jaundice (concentrated urine)
3. if red then there is blood in it
4. Green blue: decay of proteins in the intestine (Conjugation with sulphuric and glucuronic acids)
3. Urine should be transparent if cloudy there is pus or mucin in urine due to:
1. Metabolic disorders
4. Density: 1.012-1.020g/mL
1. Increased density: increase in organic/ inorganic substances due to e.g. diabetes mellitus
2. Decreased density: can be caused by diabetes insipidus
5. pH: 5.5-6.8
1. Acidic: due to diabetes mellitus, starvation, fever and meat consumption
2. Alkaline: die to Cystitis, Pyelitis and consumption of plants
6. Isostenuria: continuously low density in oliguria (kidney failure) – index for lack of Anti diuretic hormone
60. Pathological components of urine, which appear due to different metabolic disorders in organism?
Urobilinuria (brown color in urine): caused by overburdening the liver, excessive RNC breakdown, hepatic infection,
liver cirrhosis and increased urobilinogen production
Phenylketonuria (phenyl pyruvate in urine): a genetic disease caused due to the absence or deficiency of
phenylalanine 4 hydroxylase, diagnosed with FeCl3
Pyuria (cloudy urine): condition where there is pus or too many white blood cells in urine. Causes include:
Infectious causes: tuberculosis and infection of prostate
Noninfectious causes: treatment of glucocorticoids, mechanical trauma, kidney stones and tumors
Amino acid phenylalanine forms benzoic acid in tissues which is then interacts with glycine and detoxified in liver to
hippuric acids which is excreted in urine
Activity of alanine amino peptidase is tested for in urine to check for acute kidney inflammation
Proteinuria: presence of protein in urine
Proteinuria Type Pathophysiological features cause
Glomerular Increased glomerular capillary Primary or secondary
permeability to protein glomerulopathy
Tubular Decreased tubular reabsorption of Tubular or intestinal disease
proteins in glomerular filtrate
Overflow Increased production of low Monoclonal gammpathy, Leukeia
molecular weight proteins
61. General description of connective tissue. Structure and functions of collagen. Elastin–main protein of elastic
fibrils, structure and biological role?
As the name implies, connective tissue serves a connecting function. It supports and binds other tissues in the body.
Unlike epithelial tissue, which has cells that are closely packed together, connective tissue typically has cells scattered
throughout an extracellular matrix of fibrous proteins and glycoproteins attached to a basement membrane. The
primary elements of connective tissue include a ground substance, fibers, and cells.
The ground substance acts as a fluid matrix that suspends the cells and fibers within the particular connective tissue
type. Connective tissue fibers and matrix are synthesized by specialized cells called fibroblasts. There are three main
groups of connective tissues: loose connective tissue, dense connective tissue, and specialized connective tissue.
Collagenous fibers are made of collagen and consist of bundles of fibrils that are coils of collagen molecules. These
fibers help to strengthen connective tissue.
Elastic fibers are made of the protein elastin and are stretchable. They help to give connective tissue elasticity.
Reticular fibers join connective tissues to other tissues.
Loose connective tissues provide support, flexibility, and strength required to support internal organs and structures
such as blood vessels, lymph vessels, and nerves.
Dense connective tissue can be categorized into dense regular, dense irregular, and elastic connective tissues.
Dense regular: Tendons and ligaments are examples of dense regular connective tissue.
Dense irregular: Much of the dermis layer of the skin is composed of dense irregular connective tissue. The
membrane capsule surrounding several organs is also dense irregular tissue.
Elastic: These tissues enable stretching in structures such as arteries, vocal cords, the trachea, and bronchial tubes in
the lungs.
Specialized Connective Tissues
Specialized connective tissues include a number of different tissues with specialized cells and unique ground
substances.
Some of these tissues are solid and strong, while others are fluid and flexible.
Adipose
Adipose tissue is a form of loose connective tissue that stores fat. Adipose lines organs and body cavities to protect
organs and insulate the body against heat loss. Adipose tissue also produces endocrine hormones.
Cartilage
Cartilage is a form of fibrous connective tissue that is composed of closely packed collagenous fibers in a rubbery
gelatinous substance called chondrin. The skeletons of sharks and human embryos are composed of cartilage.
Cartilage also provides flexible support for certain structures in adult humans including the nose, trachea, and ears.
Bone
Bone is a type of mineralized connective tissue that contains collagen and calcium phosphate, a mineral crystal.
Calcium phosphate gives bone its firmness.
Blood
Interestingly enough, blood is considered to be a type of connective tissue. Even though it has a different function in
comparison to other connective tissues, it does have an extracellular matrix. The matrix consists of the plasma with
red blood cells, white blood cells, and platelets suspended in the plasma.
Lymph
Lymph is another type of fluid connective tissue. This clear fluid originates from blood plasma that exits blood vessels
at capillary beds. A component of the lymphatic system, lymph contains immune system cells that protect the body
against pathogens.
COLLAGEN
See Figure 6–4 for collagen structure and Figure 6–5 for collagen synthesis.
■ 1/3 of body’s protein.
■ Consists of three polypeptide a-chains wound around one another to form
a triple helix.
■ Produced by many cells: fibroblasts, epithelial cells, odontoblasts, osteoblasts,
and chondrocytes.
■ It is the organic matrix in dentin and cementum
■ 35% glycine; 21% proline; 11% alanine.
■ Fibers have high tensile strength.
COLLAGEN SYNTHESIS
■ Intracellular events
■ rER: Synthesis of a-chains with glycine-x-y sequence.
■ rER: Hydroxylation of proline and lysine residues, forming hydroxyl proline and hydroxylysine. Requires vitamin C.
■ Golgi: Glycosylation of α-chains, forming procollagen, a triple helix containing N- and C-terminal propeptides.
■ Extracellular events
■ Endopeptidases cleave the N- and C-terminal propeptides of procollagen, forming tropocollagen.
■ Cross-linking of tropocollagen molecules, forming collagen fibrils.
Requires oxidation of lysine via lysine oxidase (contains copper).
Types of Collagen
Type Location
I Skin, bone, tendon, sclera, dentin, cementum, gingiva, PDL
II Cartilage, vitreous humor
III Embryonic CT, organ CT, blood vessels, pulp, PDL
IV Basement membrane
V Widely distributed CT, dentin, gingiva, PDL
VII Anchoring fibrils of basement membrane
ELASTIN
■ Fibers are extremely elastic, “rubber-like.”
■ Found in skin, ligaments, arterial walls.
■ Synthesis can occur simultaneously with collagen.
■ Synthesized similarly to collagen:
■ Amino acid sequence of the proelastin polypeptide chain is typically glycine-x-y. Other residues include
proline, lysine, alanine, and hydroxyproline (to a lesser extent).
■ Endopeptidases cleave the N- and C-terminal propeptides of proelastin, forming tropoelastin.
■ Cross-linking of tropoelastin molecules via desmosine, forming elastin fibers. Requires oxidation of lysine
via lysine oxidase (contains copper).