Biochemistry Flashcards
what is width of plasma membrane
7-10 nm wide
what is the chemical composition of plasma membrane
43% lipids
49 % proteins
8 % carbohydrates
what are the types of lipids in cell membrane
Phospholipids (Lecithin & Cephalin)
Glycosphingolipids (Cerebrosides & Gangliosides)
Cholesterol
what is significance of lecithin in cell membrane
Lecithin is composed of units of choline, phosphoric acid, fatty acids and glycerol. … Without lecithin, the cell membranes would become less fluid, thus less permeable.
what is the significance of cephalin in cell membrane
Cephalin plays a role in membrane fusion. Fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure.
what is the function of ganliosides in cell membrane
Gangliosides is a component of the plasma membrane that modulates cell signal transduction events.
The functions of gangliosides as specific determinants suggest its important role in the growth and differentiation of tissues as well a
s in carcinogenesis.
what is the significance of cholesterol in cell membrane
Cholesterol provides stability to the plasma membrane by limiting the movement of the phospholipids.
cholesterol in the cell membrane is to maintain stability, anchor other molecules.
Cholesterol acts as a bidirectional regulator of membrane fluidity because at high temperatures, it stabilizes the membrane and raises its melting point, whereas at low temperatures it intercalates between the phospholipids and prevents them from clustering together and stiffening.
write a short note on the fatty acids in cell membrane
They are also major component of cell membrane. 50% of fatty acid groups are saturated. The other half contains unsaturated and polyunsaturated fatty acids.
Oleic acid is the most abundant unsaturated fatty acids in animal membranes.
The degree of unsaturation determines the fluidity of the membranes.
which types of proteins form the cell membrane
Integral or intrinsic proteins
Peripheral or extrinsic proteins
Trans-membrane proteins
(span the whole width )
what is integral membrane protein and write about its signifiance
An integral membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane.
IMPs include transporters, linkers, channels, receptors, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction of energy, and proteins responsible for cell adhesion. Common examples are Insulin receptors, Glycophorin, Rhodopsins. Band-3 proteins etc
what is peripheral membrane protein and its significance in cell membrane
Peripheral membrane proteins are membrane proteins that adhere only temporarily to the biological membrane with which they are associated.
Peripheral enzymes participate in metabolism of different membrane components, such as lipids (phospholipases and cholesterol oxidases).
what is transmembrane protein and write about its significance
A trans membrane protein (TP) is a type of integral membrane protein that spans entirely the cell membrane to which it is permanently attached. Many trans membrane proteins function as gateways to permit the transport of specific substances across the membrane.
what are the major functions of membrane proteins
Transport Enzymatic activity Signal transduction Cell-cell recognition Intercellular joining Attachment to the cytoskeleton and extracellular matrix (ECM)
which carbohydrates are present in cell membrane
Glycoproteins
Glycolipids
what is glycosylation
The carbohydrate is attached to the protein in a posttranslational modification. This process is known as glycosylation.
what is the significance og glycoprotein and give a detailed example
Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. One example of glycoproteins found in the body is mucins, which are secreted in the mucus of the respiratory and digestive tracts. The sugars when attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
what are glycolipids and write about their significance
Glycolipids are lipids with a carbohydrate attached by a glyosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues. They include glyceroglycolipids and glycosphingolipids.
what is glycocalyx and write about its significance
The glycocalyx, is a glycoprotein and glycolipid covering that surrounds the cell membranes. This viscous coating consists of several carbohydrate moieties of membrane glycolipids and glycoproteins, which serve as backbone molecules for support. Generally, the carbohydrate portion of the glycolipids found on the surface of plasma membranes helps these molecules contribute to cell–cell recognition, communication, and intercellular adhesion.
how are caveolae formed
The caveolae are formed by the curving inward of the inner leaflet of the plasma membrane an integral protein named caveolin forces the formation of caveolae which are involved in the membrane transport and rigidity
how are rafts formed and write about their structure
The rafts are made by the clustering of sphingolipid with cholesterol in the outer monolayer of the plasma membrane. The rafts appear to have receptors and signaling proteins.
write about the clinical significance of cell membrane
ALZHEIMER’S DISEASE: Oxidative stress in brain results in alterations in phospholipids that comprise the cell membrane and disrupts the functions of effected brain cells.
CYSTIC FIBROSIS: Defect in calcium ion channels for the unclear reasons in excess production of fluid in lungs
what are ion channels and describe their types
Ion channels are transmembrane channels, pore like structures composed of proteins”.
All channels have gates & are controlled by opening
and closing.
TYPES:
Ligand gated channels:
In this a specific molecule binds to a receptor and opens the channel.
Voltage gated channels:
These channels open or close in response to changes in membrane potential.
write a short note on simple or passive diffusion
It depends on concentration gradient of a particular substance across the membrane
The solute passes from higher concentration to lower concentration till equilibrium is reached
The process neither requires any carrier protein nor energy
write a short note on facilitated diffuision
It is similar to passive diffusion in that the solutes move along the concentration gradient.
But it differs from passive diffusion in that it requires a carrier protein or transport protein.
Energy is not required.
write a short note on active transport
It occurs against a concentration gradient
Energy is required
40% of the total energy requirement in a cell is utilized for active transport system
Carrier or transport proteins are needed
write a short note on uniport
This system involves the movement of certain substance across the plasma membrane singly and independently of any other substance
The transporter involved is called uniporter
write a short note on symport
This system involves the movement of two substances across the membrane together & in the same direction
The transporter involved is called symporter
write a short note on antiport an give an example
Also called counter transport
This system involves the movement of two different substances simultaneously, but in two different directions
Example: Efflux of 3 Na + ions to cell exterior & a simultaneous influx of 2 K+ ions
what are the mechanisms for transport of macromolecules
The mechanism of transport of macromolecules such as proteins, hormones, immunoglobulins, LDL, and even viruses takes place across the membrane by two independent mechanisms Exocytosis Endocytosis Phagocytosis = “cellular eating” Pinocytosis = “cellular drinking
what is exocytosis
In exocytosis, transport vesicles migrate to the membrane, fuse with it, and release their contents. Many secretory cells use exocytosis to export their products.
what is endocytosis
In endocytosis, the cell takes in macromolecules by forming vesicles from the plasma membrane. Endocytosis is a reversal of exocytosis, involving different proteins
describe the types of endocytosis
Phagocytosis (cellular eating): Cell engulfs particle in a vacuole
Pinocytosis (cellular drinking): Cell creates vesicle around fluid
Receptor-mediated endocytosis: Binding of ligands to receptors triggers vesicle formation
describe the activity of sodium potassium pump and its significance
Transports sodium from inside to outside the cell and at the same time pumps K+ from outside to inside the cell.
Maintain sodium and potassium concentrations
Establishing a negative electrical voltage inside the cells
Complex of two separate globular proteins
subunit, with a molecular weight of about 100,000.
β subunit, with a molecular weight of about 55,000.
It has three receptor sites for binding sodium ions on the portion of the protein that protrudes to the inside of the cell.
It has two receptor sites for potassium ions on the outside.
The inside portion of this protein near the sodium binding sites has ATPase activity
write about the primary active transport of calcium
Calcium is actively transported from inside to outside the cell by calcium pump.
Energy is obtained from ATP by the catalytic activity of ATPase.
Present in the sarcoplasmic reticulum of muscle cells and the mitochondria of all the cells.
write about the primary active transport of hydrogen ions
In the gastric glands of the stomach
Involved in the formation of hydrochloric acid
In the late distal tubules and cortical collecting ducts of the kidneys
Hydrogen ions are secreted from the blood into the urine
what is the biochemical importance of carbohydrates
Glucose is major metabolic fuel for mammals & is precursor for synthesis of all other carbohydrates in the body
Glycogen for storage
Ribose & deoxyribose in nucleic acids
Galactose in the lactose of milk (milk sugar)
Carbohydrates occurs in cell membranes as glycoproteins & glycolipids
Present in lipoproteins
Diseases related to CHO metabolism include galactosemia, lactose intolerance, glycogen storage diseases, diabetes mellitus
what are carbohydrates
Poly hydroxy aldehydes
or
Poly hydroxy ketones
describe classification of carbohydrates
Monosaccharides Disaccharides Oligosaccharides Polysaccharides Derived carbohydrates
write a short note on monosaccharides
Monosaccharides are simple sugars
Can not be further hydrolyzed
A carbonyl group (aldehyde or ketone) & several hydroxyl groups
Eg. Glucose, fructose, galactose
General formula (CH2O)n ( n= 3 or some larger number
write a short note on disaccharides
Those sugars which yield two molecules of the same or different monosaccharides on hydrolysis
The two monosaccharides are linked by a glycosidic bond
Eg. lactose, sucrose, maltose, isomaltose, trehalose
General formula Cn(H2O)n-1
what are glucose dimers
Maltose α 1-4 linkage…..isomaltose α 1-6 linkage…..trehalose α 1-1 linkage…..all are glucose dimers
write a short note on oligosaccharides
Those sugars which yield 3 to 10 monosaccharides on hydrolysis
Monosaccharides are joined to each other covalently through O- glycosidic bonds or linkages
E.g α dextrins ( polymer of eight glucose molecules)
write a short note on polysaccharides
Those sugars which yield more than 10 molecules of monosaccharides on hydrolysis
General formula (C6H10O5)n
Further divided into
Homopolysaccharides (homoglycans)
Heteropolysaccharides (heteroglycans)what are homopolysaccharides
Polymer of same monosaccharide units
Eg . Starch, glycogen, dextrin, dextran, cellulose
what are heteropolysaccharides
Polymer of different monosaccharide units
Eg. Mucopolysaccharides ( GAGs)
Glycoconjugates, Mucilages
write a short note on complex/derived carbohydrates and their examples
Derived from carbohydrates by various reactions
Eg. Oxidation products, reduction products, amino sugars, deoxy sugar
Oxidation… gluconic acid glucaric acid ascorbic acid……. Reduction… polyhydroxy alcohols-glycerol….. Amino sugar ….glucosamine….. Deoxysugar… deoxyribose
monosaccharides can be classified into
aldoses
ketoses
aldoses can be classified into ——– according to number of carbon atoms
triose (3 C atoms) (glyceraldehyde) tetrose (4 C atoms) (erythrose) pentose (5 C atoms) (ribose) hexose (6 C atoms) (glucose, galactose, mannose) heptose (glucoheptose)
ketoses can be classified into ——— according to number of carbon atoms
tritulose (dihydroxy acetone) tetrulose (4 C atoms) (erthrulose pentulose (5 C atoms) (ribulose) hexulose (6 C atoms) (fructose) heptulose (sedoheptulose)
what are disaccharides and give some examples
A disaccharide consists of two monosaccharides.
Glucose + Glucose Maltose + H2O
Glucose + Galactose Lactose + H2o Glucose + Fructose Sucrose + H2o
what is fisher projection
straight chain representation
3D structure of stereoisomers can easily be drawn and represented in 2D
what is harworth projection
simple ring in perspective
what are conformational representation
chair and boat configuration
what are hemiacetal and hemiketal
aldehyde and alcohol from hemiacetal
ketone and alcohol form hemiketal
write a short note on D-glucose
Found in fruits, corn syrup, and honey.
An aldohexose with the formula C6H12O6.
Known as blood sugar in the body.
The monosaccharide in polymers of starch, cellulose, and glycogen.
write a short note D-fructose
Is a ketohexose C6H12O6.
Is the sweetest carbohydrate.
Is found in fruit juices and honey.
Converts into glucose in the body.
write a short note on D - galactose
An aldohexose C6H12O6 Not found free in nature. Obtained from lactose, a disaccharide A similar structure to glucose except for the –OH on C4.
how are glyosidic bonds formed
Glycosidic bonds are formed by the enzymes glycosyl transferases that use nucleotide sugars as substrate
write a short note on maltose
Maltose, a cleavage product of starch (e.g., amylose), is a disaccharide with an a(1® 4) glycosidic link between C1 - C4 OH of 2 glucoses.
It is the a anomer (C1 O points down).
write a short note on sucrose
common table sugar, has a glycosidic bond linking the anomeric hydroxyl of glucose & fructose, the linkage is α (12)
write a short note on lactose
milk sugar, is composed of galactose & glucose, with β (14) linkage from the anomeric OH of galactose
what is inversion phenomenon
In free form fructose occurs in pyranose form which is strong levorotatory
Rotation is reversed & process is called inversion phenomenon
Product of sucrose hydrolysis ( fructose) is called invert sugar
write a short note on reducing and non-reducing sugars
Sugars having atleast one free aldehyde or keto group in their structure are Reducing sugars
Those which do not have any free active group (aldehyde or keto) are known as Non-reducing Sugars
All monosaccharides & disaccharides are reducing except sucrose
A non-reducing sugar can be hydrolyzed using dilute hydrochloric acid. After hydrolysis and neutralization of the acid, the product may be a reducing sugar
what are structural and storage polysaccharides
Storage polysaccharides contain only α-glucose units. Important ones are starch & glycogen
Structural polysaccharides contain only -glucose units. Important ones are cellulose and chitin. Chitin contains a modified -glucose unit
write a short note on starch
Starch is a storage compound in plants, and made of αD-glucose units
It is a homo-polymer of glucose made up of two components: amylose and amylopectin.
Starch is 15-20% amylose and 80-85% amylopectin
It is also non-reducing (because no potential aldehyde group
describe amylose
Amylose – a straight chain structure formed by α 1→4 glycosidic bonds between α-D-glucose molecules.
The amylose chain forms a helix or coiled structure
describe amylopectin structure
Amylopectin-a glucose polymer with mainly α -(14) linkages, but it also has branches formed by α -(16) linkages
what is the action of enzymes on starch
Salivary & pancreatic amylases (α-amylases) hydrolyze starch into
Maltose
Maltotriose
α- dextrins
write a short note on starch
Structural polysaccharide
It is an unbranched polymer of -D-glucose mainly present in plant kingdom
Consists of large number of glucose residues joined to each other through (1→4) linkages
Cellulose is made up of repeating disaccharide units called cellubiose
Cellubiose has same structure as maltose, but unlike maltose it has (1→4) glycosidic linkage
write about significance of cellulose
Cellulose is important in our diet because it
Provides fiber & bulk to the food
Serves to satisfy appetite
& Assists with digestive movements in the small and large intestine
Humans can not digest cellulose because they lack the enzyme cellulase to hydrolyze the (1→4) glycosidic bond
write a short note on glycogen
Homo-polymer of α D-glucose
Storage polysaccharide also known as animal starch
Present in liver & muscles
Resembles amylopectin but it is more compact
A glucose polymer with mainly α -(14) linkages, but also has branches formed by α -(16) linkages
Glycogenesis
Glycogenolysis
what are dextrins
Intermediate products in the hydrolysis of starch by acids or enzyme amylase
Each dextrin molecule consists of 8 α D-glucose residues showing mostly α -(14) linkages in addition to α -(16) linkage at each of branching site
Sweet in taste
what are dextrans
Dextrans homo-polymer of α D-glucose residues
Showing mostly α -(16) linkages in addition to (12), (13) & (14) linkages
Used in medicine as plasma substitute or plasma extender in the treatment of hypovolemic shock
what are lipids
Heterogeneous group of organic compounds”
Soluble in organic solvents but in soluble in water
what is the biomedical importance of lipids
High energy dietary constituent Lipoprotein (lipid transporter) Structural components (plasma membrane) Protective covering to internal organs Production of hormones Fat soluble vitamins
lipids are classified into
simple lipids
compound lipids
derived lipids
simple lipids are derived into
fats
waxes
simple fats are
neutral fats/ triglycerides
esters of fatty acids with glycerol
what are waxes and their types
Esters of fatty acids with long chain alcohols 1. True Waxes Bees Wax, Lanolin, Spermaceti 2. Others Waxes Cholesterol Esters, Vitamins A & D Lipase can not hydrolyze waxes
compound lipids include
phospholipids sulfolipids gangliosides glycolipids lipopolysaccharides lipoproteins
phospholipids include
glycerophospholipids
(lecithin, cephalin, plasmalogens)
sphingophospholipids
(sphingomyelins)
derived lipids include
diglyceride fatty acids alcohols cholesterol fat soluble vitamins
what are fatty acids and their characteristics
“Aliphatic Mono-carboxylic Acids”
Double bonds are always spaced at 3-Carbon intervals from each other
Numbered from carboxyl end
CH3-R-COOH
Even number of carbon atoms
Unbranched
Saturated or unsaturated
Cis or Trans
what are the properties of enzymes
Protein catalysts ( except Ribozymes)
Increases the velocity of chemical reactions
Not consumed during reactions they catalyze
what are catalysts
Speeds up chemical reactions in living organisms by decreasing the energy needed to start the reaction (activation energy)
describe the location of enzymes
Enzymes are localized in specific organelles within the cell
This isolation separates reaction substrates or products from other competing reactions
what are characteristic of enzymes
Enzymes are highly specific, interacting with one or few substrates & catalyzing only one type of chemical reaction
Enzyme catalyzed reactions are faster than un catalyzed reactions
Each enzyme molecule is capable of transforming 100-1000 substrate molecules into product each second.
what is turnover number
The number of molecules of substrate converted to product per enzyme molecule per second is called the turnover number
what are the mechanisms of enzyme catalysis
Lock & key model
Induced fit model
what is lock and key hypothesis
Enzyme and substrate both are rigid structures
Both fit in each other just like a specific key fix in a lock
what is induced fit model
Enzyme will induce change in its shape when substrate comes close to fit in it
what are the classifications of enzymes
site of action (intracellular/extracellular)
source of enzymes (plants, animals)
chemical composition (simple/conjugated)
type of reaction (hydrolase, oxidase, dehydrogenase)
type of substrate(proteinn, carb, lipids)
what is composition classification of enzyme
simple enzymes (composed completlyof protein)
complex enzymes (composed of protein plus non-protein part)
holoenzymes are complex enzymes
protein component is called apoenzyme
what is holoenzyme
active enzyme with its non-protein component
what is co-factor
non protein part
usually metal ion of iron and zinc
what is co enzyme and its types
Non-protein part is a small organic molecule
Coenzyme A & NAD+
Transiently associated coenzyme = Co-Substrate
Permanently associated coenzyme= Prosthetic Group
what are the factors that affect enzyme activity
Enzyme concentration Substrate concentration Temperature pH Product concentration Presence of cofactors, coenzymes & prosthetic group Inhibitors
what is the effect of enzyme concetration on rate of reaction
directly proportional
what is the effect of substrate concetration on rate of reaction
Enzyme reaction is directly proportional to the substrate concentration
Substrate concentration α velocity of reaction
When the maximum velocity is achieved the increasing concentration of substrate does not further increase the reaction rate
what is the effect of temperature on rate of reaction
Optimum temperature
Humans … 35 C- 40 C
The reaction velocity increases with temperature until a peak velocity is reached
Further elevation of the temperature results in a decrease in reaction velocity
(denaturation of the enzyme)
what is the effect of ph on rate of reaction
Enzymatic activity is maximum at optimum pH
Optimum pH is different for different enzymes
e.g Pepsin —pH 2
Extreme changes in pH may denature enzyme
The reaction rate is decreased
what is the effect of product conc on rate of reaction
Excess of products may lower the enzymatic reaction by occupying the active site of the enzyme
Reaction slows down or stops
what is the effect of inhibitors on rate of reaction
Enzymes are proteins which can be inactivated by the agents known inhibitors & this process is known as enzyme inhibition
Inhibitors of enzymes generally resemble particular enzymes substrate(s)
Many therapeutic drugs are some type of enzyme inhibitor
what is optimum ph for enzymes in humans
Optimum pH of most enzymes is 4-9
Exceptions:
Digestive enzymes in stomach (pH 2)
Digestive enzymes intestine (pH 8)
what are inhibitor and their types
Enzyme inhibitors inhibits the enzyme activity
Two types
Reversible inhibition (noncovalent bonds)
Competitive
Noncompetitive (mixed)
Uncompetitive
Irreversible inhibition (covalent bonds)
what are reversible competitive inhibitors
These are chemicals that resemble an enzyme’s normal substrate and compete with it for the active site
Increasing the conc. of substrate can reverse this type of inhibition
what are reversible non-competitive inhibitors
Do not enter the active site, but binds to another part of the enzyme change its shape & alters the active site
Increasing the conc. of substrate cannot reverse this type of inhibition
what is non-competitive inhibition
An uncompetitive inhibitor binds to the enzyme substrate complex but not to free enzyme
The effect of an uncompetitive inhibitor can not be overcome by high concentrations of the substrate
Result in the destruction or modification of an essential amino acid required for enzyme activity
Suicide inhibitors
what are allosteric enzymes
Allosteric means “occupy different sites”
In addition to active sites these enzymes possess other sites where certain reagents called effectors ( modifiers & modulators) can bound
Non-covalent linkages
e.g cAMP, cGMP
Allosteric enzyme + effector = change in 3 dimensional structure of enzyme
Inhibition or activation of enzyme activity
what are nucleic acids
These are non protein nitrogenous substances made up of a monomeric unit called a nucleotide.
what are nucleic acids and its types
These are non protein nitrogenous substances made up of a monomeric unit called a nucleotide.
DNA and RNA
what are nucleic acids types
DNA and RNA
what are the bases and nucleosides
adenine (adenosine) guanine (guanosine) cytosine (cytidine) uracil (uridine) thymine (thymidine)
what is nucleoside
base plus sugar
what the nucleosides in DNA
ATGC
what are the nucleosides in RNA
AUGC
what are purines and examples
two rings structure
AG
what are pyrimidine
one ring structure
TCU
what is the significance of phosphate group
Used to form phosphodiester linkage between 5’ and 3’ carbons of adjacent nucleotides in order to form polynucleotide chains.
number of hydrogen bonds between two nucleotides
AT 2
AU 2
GC 3
structure of DNA is
double stranded helix
describe detailed structure of DNA
In crystalline DNA the bases are separated by 0.34nm and each base is rotated 36 in relation to the previous base .
The helical structure repeats at interval of 3.4nm .
Therefore there are 10 base pairs in each completed helix .
The helix is 2nm in diameter .
The molecule shows a minor groove and a major groove .
These grooves wind along the molecule parallel to the phosphodiester linkage .
These grooves serves to accommodate proteins which binds with specific nucleotide sequences without disturbing the base pairing of double helical DNA molecule
what are the types of DNA replication
conservative
semi-conservative
write a short note on DNA replication
DNA in the chromosomes replicates itself every cell division .
Maintains correct genetic information .
Two strands of DNA unwind .
Each strand acts like a template .
New bases pair with their complementary base.
Two double helixes are formed that are copies of original DNA .
why is DNA called genetic material
Present in all cells and virtually restricted to the nucleus .
The amount of DNA in somatic cells (body cells) of any given species is constant (like the number of chromosomes) .
The DNA content of gametes (sex cells) is half that of somatic cells.
In cases of polyploidy (multiple sets of chromosomes) the DNA content increases by a proportional factor .
The mutagenic effect of UV light peaks at 253.7nm. The peak for the absorption of UV light by DNA .
why do we need both DNA and RNA
DNA holds all the genetic information/instructions for the proteins produced in a cell so why do we need RNA.
It is bcause DNA holds all the genetic information, this means it is Extremely important.
If DNA is damaged in any way, the coding sequence can change and a mutationwill arise that will potentially influence the particular protein and perhaps the whole cell or organism.
If DNA ventured into the cytoplasm to give instructions for protein synthesis it would be vulnerable to damage from chemicals, UV radiation and other mutagens.
RNA acts as a massenger. Damage to mRNA will not permanently affect function of the cell as the DNA template is undamaged.
what are the steps involved in DNA replication
Identification of site of origin of replication
Unwinding the DNA molecule
Formation of replication fork
Initiation and elongation
Formation of replication bubble and ligation
describe the process of unwinding in DNA molecule
Replication of DNA begins at a sequence of nucleotides called the origin of replication.
An enzyme called helicase unwinds the dsDNA helix and single-stranded binding proteins (SSBP) react with the ssDNA and stabilize it.
At the same time, DNA gyrase relieves the strain that unwinding causes on the molecule by cutting, winding and rejoining DNA strands.
Under an electron microscope the unwound section looks like a “bubble” and thus is known as the replication bubble.
describe step of the formation of new stands in DNA replication
DNA polymerase III is the major enzyme involved in DNA replication.
It adds nucleotides to the 3’ end of a pre-existing chain of nucleotides thus generating a new complementary strand of DNA, but it cannot initiate a nucleotide chain.
An RNA polymerase called primase is needed to start a new nucleotide chain.
Primase constructs an RNA primer (sequence of about 10 nucleotides complementary to the parent strand) which DNA polymerase III can then add nucleotides to.
The unwound DNA exposes two parental strands of DNA which are antiparallel. This means they are orientated in different directions and must be replicated by different mechanisms.
The leading strand elongates towards the replication fork (in the direction of unwinding) by the simple addition of nucleotides to is 3’ end by DNA polymerase III.
The lagging strand must elongate away from the replication fork. It is synthesized discontinuously as a series of short segments called Okazaki fragments. When DNA polymerase III reaches the RNA primer on the lagging strand, it is replaced by DNA polymerase I, which removes the RNA primer and replaces it with DNA. DNA ligase then attaches and forms phosphodiester bonds.
Since each new strand is complementary to its old template strand, two identical new copies of the DNA double helix are produced during replication.
In each new helix, one strand is the old template and the other is new synthesised, therefore replication is said to be semi-conservative.
The two DNA molecules rewind into the double-helices, then each double-helix is coiled around histone proteins and further wrapped up to form separate chromatids (still joined by a common centromere).
The two chromatids will become separated in the cell division process to form two separate chromosomes
what is transcription
Process of RNA synthesis from DNA template is called transcription.
write a detailed note on transcription of DNA
Process of transcription begins when a section of DNA (a gene) unwinds and the bases separate exposing two single strands of DNA with unpaired bases.
One of these strands act as a template for the formation of an mRNA molecule (it is transcribed).
Individual nucleotides of RNA align with the exposed bases on the DNA template according to base pairing rules. And nucleotides are added to 3’ end of growing RNA molecule.
The formation of the mRNA molecule is catalysed by the enzyme RNA polymerase.
This molecule is actually referred to as pre-mRNA. It is complementary to the template strand but requires some post-transcriptional modification.
Post-transcriptional modification of pre-mRNA or nuclear mRNA involves the removal of introns (non-coding regions within genes) and stitching together of exons (coding regions of genes). This process is known as RNA splicing.
Following RNA splicing a chemical cap is added to the 5’ end of the molecule and a poly-A tail (string of A nucleotides) to the 3’ end. The 5’ cap enables efficient protein synthesis as it is part of the structure recognized by the small ribosomal subunit. The poly-A tail is also important for initiating translation. It also has a role in regulating the degradation of mRNA molecules in the cytoplasm.
what is translation
It is the process by which RNA synthesizes proteins.
write a detailed note on transcription of mRNA
mRNA exits the nucleus through nuclear pores and binds to ribosomes within the cytoplasm.
Translation of mRNA begins with the sequence AUG (start codon).
Transfer RNAs (tRNA) bring specific amino acids to the ribosome and these are added to the growing polypeptide chain by condensation polymerisation. New amino acids are added to the carboxyl (COOH) end of the polypeptide.
The tRNA drops away from the mRNA and acquires another specific amino acid from the pool in the cytoplasm. Each tRNA can only carry one type of amino acid.
Translation ends when the ribosome reaches a stop codon – the tRNA molecules corresponding to the stop codons UAG, UGA and UAA don’t carry a amino acid.
The mRNA is then released from the ribosome .
what are interons
sequences in the DNA that are not used to make mRNA or to make proteins
they are not transcribed
what are exons
sequences in the DNA that are expressed or used to make mRNA and ultimately are used to make proteins
what is codon
Codon is the message on mRNA for specific aminoacid required for the protein, which is to b synthesized.
Each codon consists of 3 consecutive nitrogenous bases ,e.g for phenylalanine there are two codons i.e UUU and UUC .
what is anticodon
Every codon has its specific anti codon . Anti codon has a sequence of 3 nitrogenous bases, which give the tRNA the specific property to recognize the site of codon present on mRNA.
Nitrogenous bases of anti codon are complementary to the nitrogenous bases of the codons.
what is post translational modification
It is the modification of proteins after they have been synthesized .
Proteins may b modified by phosphorylation, glycosylation ,hydroxylation and addition of other groups .
describe the four types of RNA
Messenger RNA (mRNA) Copied portion of coding DNA Carries genetic information from the DNA out of the nucleus into the cytoplasm
Transfer RNA (tRNA) Transports amino acids to the ribosome during protein synthesis
Ribosomal RNA (rRNA) Structural component of ribosomes
snRNA (snRNA)
Involved in splicing of pre-mRNA message in the nucleus to remove introns
describe the structure of tRNA
Also called soluble RNA
Largely in cytoplasm
Small and single stranded
At least 20 different tRNA molecules
Consists of 75 nucleotides
Their basis include
A , G , C , U , pseudouridine ,
uracil 5 ribofuranoside and thymine
in one loop
A clover leaf structure
H- bonds between bases
All tRNA molecules contains 4 arms r loops
Once a tRNA gene is transcribed, the RNA that is produced folds to form the shape of a three-leafed clover. This is a functional tRNA molecule.
This tRNA is charged with the amino acid lysine at the amino acid attachment site. The anticodon UUU will bind to the complementary AAA sequence in the mRNA
what are the sources of calcium
• Sources in the diet • Milk • Yogurt • Cheese • Dark green vegetables • Fortified sources • Cereals • Bread • Orange Juice broccli figs spinach sesame seeds cabbage
what is daily requirement of calcium
Daily Recommended Intakes
• 9-18 years = 1300 mg
• 19-50 years = 1000 mg
• 51 years and older =1200 mg
what are he functions of calcium
Major component of bones and teeth •A small amount of calcium circulates in the blood •Essential for clotting of the blood •Aids in the normal functioning of the nerves, muscles, and heart
• Ca salts in bone provide structural integrity of the skeleton.
• Ca is the most abundant mineral in the body.
• The amount of Ca is balance among intake, storage, and
excretion.
• This balance is controlled by transfer of Ca among 3
organs: intestine, bone, kidneys.
• Ca ions in extracellular and cellular fluids is essential to
normal function of a host of biochemical processes
• Neuoromuscular excitability and signal transduction
• Blood coagulation
• Hormonal secretion
• Enzymatic regulation
• Neuron excitation
who is at risk of calcium deficiency
- Children and youth
- Post-menopausal women
- Elderly
- People with poor diets, lacking in dairy food
how to reduce risk of osteoporosis
Calcium in the diet
• habitual exercise
• avoidance of smoking and alcohol intake
• avoid drinking carbonated soft drinks
describe the formation and resorption of bone with respect to age and gender
The total bone mass of humans peaks at 25-35 years of age.
•Men have more bone mass than women.
•A gradual decline occurs in both genders with aging, but women
undergo an accelerated loss of bone due to increased resorption during
perimenopause.
•Bone resorption exceeds formation.
what is the relationship of calcium with blood
Ca2+ normally ranges from 8.5-10 mg/dL in the plasma.
•The active free ionized Ca2+ is only about 48% 46% is bound to
protein in a non-diffusible state while 6% is complexed to salt.
•Only free, ionized Ca2+ is biologically active.
what is the relationship of calcium with bone
• 99% of Ca is found in the bone. Most is found in hydroxyapatite
crystals. Very little Ca2+ can be released from the bone– though it is
the major reservoir of Ca2+ in the body.
describe the intake of calcium
•About 1000 mg of Ca is ingested per day.
•About 200 mg of this is absorbed into the body.
•Absorption occurs in the small intestine, two mechanisms ve been
proposed for absorption of calcium by gut mucosa
1/ simple diffusion and
2/ active transport .
describe the storage of calcium
•The primary site of storage is our bones (about
1000 grams).
• Some calcium is stored within cells (endoplasmic
reticulum and mitochondria).
•Bone is produced by osteoblast cells which
produce collagen, which is then mineralized by
calcium and phosphate (hydroxyapatite).
•Bone is remineralized (broken down) by
osteoclasts, which secrete acid, causing the release
of calcium and phosphate into the bloodstream.
•There is constant exchange of calcium between
bone and blood
describe the excretion of calcium
The major site of Ca excretion in the body is the
kidneys.
•The rate of Ca loss and reabsorption at the kidney
can be regulated.
•Regulation of absorption, storage, and excretion of
Ca results in maintenance of calcium homeostasis
describe the characteristics of plasma calcium and its subfractions
•Occurs in two forms.
Non- diffusible; This fraction cannot be dialyzed out bcoz it is in firm
combination with negatively charged plasma proteins specially albumin
and immunoglobulin.
Its level is 3.4 to 4.4mg/dl
Diffusible; It can b dialyzed out. It occurs in two subfractions.
• Ionized calcium
• Complexed calcium
•Ionized calcium 50%
• Protein-bound calcium 40%
• 90% bound to albumin
•Remainder bound to globulins
•Calcium complexed to serum constituents 10%
•Citrate and phosphate
•The normal level of plasma calcium is 9-10 mg / dl
•About 0.5 – 1 % of bone calcium is freely exchangeable
i.e in chemical equilibrium with calcium in ECF
•The exchange process is regulated primarily by the PTH, Active
Vitamin D & Calcitonin
what are the factors affecting calcium level in plasma
- Intestinal absorption
- Excretion in urine
- Amount of Ca absorbed from GIT
- Parathyroid hormone
- Inverse relation between plasma Ca and P levels
- Plasma protein level
- Renal excretion
- calcitonin
what are the actions of parathyroid hormone on bone
PTH acts to increase degradation of bone (release
of calcium).
- causes osteoblasts to release cytokines, which
stimulate osteoclast activity
- stimulates bone stem cells to develop into
osteoclasts
- net result: increased release of calcium from bone
- effects on bone are dependent upon presence of
vitamin D
describe PTH general characteristics
PTH is synthesized and secreted by the parathyroid
gland which lie posterior to the thyroid glands.
•The blood supply to the parathyroid glands is from
the thyroid arteries.
•The Chief Cells in the parathyroid gland are the
principal site of PTH synthesis.
•It is THE MAJOR of Ca homeostasis in humans.
how is PTH regulated
The dominant regulator of PTH is plasma Ca2+
.
• Secretion of PTH is inversely related to [Ca2+].
•Maximum secretion of PTH occurs at plasma Ca2+ below 3.5 mg/dL.
•At Ca2+ above 5.5 mg/dL, PTH secretion is maximally inhibited.
describe the action of PTH
•The overall action of PTH is to increase plasma Ca2+ levels and
decrease plasma phosphate levels.
• PTH acts directly on the bones to stimulate Ca2+ resorption and kidney
to stimulate Ca2+ reabsorption in the distal tubule of the kidney and to
inhibit reabosorptioin of phosphate (thereby stimulating its excretion).
• PTH also acts indirectly on intestine by stimulating 1,25-(OH)2
-D
synthesis.
what is the relationship between calcium and phosphate
Ca is tightly regulated with P in the body.
• P is an essential mineral necessary for ATP, cAMP 2nd messenger
systems, and other roles
describe calcitonin with respect to calcium regulation
•Calcitonin acts to decrease plasma Ca2+ levels.
•While PTH and vitamin D act to increase plasma Ca2+
– only
calcitonin causes a decrease in plasma Ca2+
.
•Calcitonin is synthesized and secreted by the parafollicular cells of the
thyroid gland.
•They are distinct from thyroid follicular cells by their large size, pale
cytoplasm, and small secretory granules.
•Role of calcitonin in normal Ca2+ control is not understood—may be
more important in control of bone remodeling.
•Used clinically in treatment of hypercalcemia and in certain bone
diseases in which sustained reduction of osteoclastic resorption is
therapeutically advantageous.
•Chronic excess of calcitonin does not produce hypocalcemia and
removal of parafollicular cells does not cause hypercalcemia. PTH and
Vitamin D3 regulation dominate.
•May be more important in regulating bone remodeling than in Ca2+
homeostasis.
The major stimulus of calcitonin secretion is a rise in plasma Ca2+
levels
•Calcitonin is a physiological antagonist to PTH with regard to Ca2+
homeostasis
The target cell for calcitonin is the osteoclast.
•Calcitonin acts via increased cAMP concentrations to inhibit
osteoclast motility and cell shape and inactivates them.
•The major effect of calcitonin administration is a rapid fall in Ca2+
caused by inhibition of bone resorption.
what are the actions of calcitonin
•The major action of calcitonin is on bone
metabolism.
•Calcitonin inhibits activity of osteoclasts, resulting
in decreased bone resorption (and decreased
plasma Ca levels).
how does vitamin D facilitate calcium absorption
It facilitates intestinal absorption of calcium, as
well as stimulates absorption of phosphate and
magnesium ions.
In the absence of vitamin D, dietary calcium is not
absorbed at all efficiently.
Vitamin D stimulates the expression of a number of
proteins involved in transporting calcium from the
lumen of the intestine, across the epithelial cells
and into blood.
The vitamin D form, 1,25-dihydroxcholecalciferol
[1,25(OH)2D3],
•stimulates the synthesis of the epithelial calcium channels in the
plasma membrane calcium pumps , and
• induces the formation of the calbindins.
Once joined with ingested vitamin D, facilitate
increased serum calcium levels
Shows Expressed Calbindins and How this facilitate
transport of Calcium through the Membranes
•Calcium absorption is transport across the epithelial cell,
which is greatly enhanced by the carrier protein calbindin, the
synthesis of which is totally dependent on vitamin D
describe excretion of calcium
Reabsorption occurs in proximal convoluted tubules, thick ascending
loop of Henle and in distal convoluted tubules amounting to 65%,
20%, and 10% respectively.
1… is coupled to Na+ reabsorption and takes place paracellularly.
2… is helped by protein paracellin & also paracellularly.
3… is occuring transcellularly. Ca enters the luminal surface of the
cell through apical Ca channels followed by its entry into cell interior
with calcium binding proteins Calbindin- D 28 K.
what are the factor affecting absorption of calcium
Ph of intestinal milieu •Composition of the diet a) high protein diet b) fatty acids c) minerals d) sugars and organic acids • State of the health of the individual and old age •Hormonal a) PTH b) calcitonin c) glucocorticoids
what is hypo and hyper calcium with their causes
Hypercalcemia
Serum calcium level exceeds 11.0 mg/dl
- Hyperparathyroidism
- Malignancy
- Over dosage of vitamins
- Drug induced hypercalcemia
- Acute renal failure
Hypocalcemia
When serum calcium less than 8.5mg/dl
- Hypoparathyroidism
- Renal disease
- Hypoalbuminaemia
- Neonatal hypocalcemia
what are macrominerals
required in amounts greater than 100mg/dl
what are microminerals
required in amount less than 100mg/dl
name the macrominerals
calcium MG K S Cl P Na
what is the requirement of phosphorus
WBC contain 47mg P /dl as inorganic phosphate
RBC contain more P than plasma
Plasma contain more phosphorus than plasma
it plasma level is 3-4.5 mg/dl in adults
plasma level in children is 4-7 mg/dl (due to growth hormone)
dietary requirement is 1.5g
sources of P are
cheese
milk
nuts
egg
sources of iron are
Animal sources are the best and include liver, meat & egg yolk.
• Plant sources include spinach and green leafy vegetables.
• Milk is very low in iron.
• Cooking in iron utensils increases iron content of food
what is the function of iron
Helps in the formation of very important structures and compounds of the body e.g • Hemoglobin • Myoglobin • Cytochromes • Catalase
describe absorption of iron
Only 10% of ingested iron is absorbed.
• Absorption takes place at mid jejunum.
• Iron is first converted to ferrous form.
• It enters the intestinal mucosal cells by an energy dependant
transport mechanism.
• From the mucosal cells iron enters the plasma
factors that increase iron absorption are
Increased erythropoieses e.g. At high altitude ,blood loss.
• Decreased iron stores e.g. In iron deficiency anemia and also after multiple
pregnancies.
• Increased iron absorption e.g. in case of taking vitamin C with iron.
• Inorganic form e.g. In iron supplements is absorbed very quickl
factors that decrease iron absorption are
• Malabsorption as in steatorrhea, celiac disease.
• Diarrhoea because there is less time for iron to stay in intestine.
• Excess of phosphates and oxalates because these make insoluble
complexes with iron preventing its absorption.
• Antacid therapy.
describe loss of iron from the body
- Males ….0.5 -1 mg of iron /day
- Females….35-70 ml of blood/day
- Women lose iron during and after pregnancy
describe iron deficiency
• Iron deficiency leads to Hypochromic- microcytic anaemia
what are the causes of iron deficiency
Nutritional deficiency of iron
• Lack of absorption: Subtotal gastrectomy and hypochlorhydria
• Hookworm infection: One hookworm will cause the loss of
about 0.3 mL of blood per day.
what is the required daily intake of iron
Adult - 20 mg of iron
•
• Children between 13–15 years need 20–30 mg/day.
• Pregnant women need 40 mg/da
sources of copper and its content in body
The body contains about 100mg coThe body contains about 100mg
copper distributed in different organs.
• Liver is the richest source
• Copper distributed in different organs.
describe absorption and secretion of cooper from the body
Only 5-10% of the ingested Cu is absorbed mainly in duodenum and
the remaining passes out in feces.
• Metallothionein is a transport protein that facilitates copper
absorption.
• Zinc and Molybedenum decrease copper uptake
what are copper containing substances in the body
Ceruloplasmin • Erythrocuprin • Cerebrocuperin • Copper containing enzymes: • Cytochrome oxidase • Catalase • Tyrosinase • Monoamine oxidase
what are the functions of copper
Copper is an essential constituent of several enzymes:
• Cytochrome oxidase
• Catalase
• Tyrosinase
• Monoamine oxidase
• Hemoglobin synthesis
• Lysyl oxidase (Cu containing enzyme):
• It is required for the conversion of certain lysine residues of collegen and
elastin to allysine which are necessary for cross-linking these structural
proteins.
• Ceruloplasmin serves as ferroxidase and is involved in the conversion of
iron from Fe⁺⁺ to Fe⁺⁺⁺ ,a form in which iron is transported in plasm
Copper is necessary for the synthesis of melanin and phospholipids.
• Development of bone and nervous system require Cu.
• Hemocyanin, a copper protein complex in invertebrates, functions
like hemoglobin for O₂ transpor
what is RDA of copper
Adults __ 2-3 mg/day
• Infants and children__ 0.5-2 mg/day
what are the clinical disorder associated with copper
- Wilson’s disease
* Menke’s disease
describe wilsons disease
Hepatolenticular degeneration)
• In liver, lenticular nucleus of brain and the descements membrane of
the cornea.
• Diagnostic feature is the presence of Kaeyser Fleischer ring in
the cornea
describe menke’s disease
Genetic disorder of poor Cu++ absorption.
• Failure to grow
• Mental deterioration
• Degenerative changes in the metaphysis
and in the elastin of aorta
what are sources of zinc
shellfish
poultry
meat
mushrooms
legumes
whole grains
what is the RDA of zinc
• Men: 11 mg/day
• Women: 8 mg/day
• The total content of zinc in an adult body is about 2 g.
• Erythrocytes contain higher content of Zn (1.5 mg/dl) which is
found in association with the enzyme carbonic anhydrase
what are the functions of zinc
It is an essential component of several enzymes e.g
Carbonic anhydrase, Alkaline phosphatase etc
• It may be regarded as an antioxidant since the enzyme superoxide dismutase
protects the body against free radical damage.
• The storage and secretion of insulin from β-cells of pancreas require Zn.
• It is required for wound healing
• Gusten, a zinc containing protein of the saliva, is important for taste
describe zinc deficiency
• Zinc deficiency is associated with growth retardation, poor wound
healing, anaemia, loss of appetite, loss of taste sensation, impaired
spermatogenesis .
• Deficiency of Zn may result in depression, dementia and other
psychiatric disorders.
• Acrodermatitis Enteropathica:
Rare inherited metabolic disease of zinc deficiency caused by defect
in Zn absorption from intestine.
describe zinc toxicity
Is often observed in welders due to inhalation of zinc oxide fumes.
• Manifested by nausea , gastric ulcer , pancreatitis and excessive
salivation
what are the sources of sulfur
meat fish eggs cheese tea cocoa dried apricots
what are the functions of sulfur
Sulfur containing amino acids are important constituents of body
proteins.
• The disulfide bridges keep polypeptide units together, e.g. insulin,
immunoglobulins.
• Chondroitin sulfates are seen in cartilage and bone.
• Keratin is rich in sulfur, and is present in hair and nail
• Co-enzymes derived from thiamine, biotin, pantothenic acid and
lipoic acid also contain sulfur.
• Sulfates are also important in detoxification mechanisms, e.g.
production of indoxyl sulfate
describe content, absorption, excretion of iodine
• The total body contains about 20 mg iodine, most of it (80%) being
present in the thyroid gland.
• It is mainly absorbed from the small intestine.
• Iodine absorption also occurs through skin and lungs.
• Its excretion mostly occurs through kidney & also through saliva, bile,
skin and milk (in lactating women)
what is the RDA of iodine
ADULTS ➔ 100-150 µg/day
• PREGNANT WOMEN ➔ 200 µg/day
what are the sources of iodine
Sea foods • Drinking water • Vegetables • Fruits • Iodized salt
describe deficiency of iodine
- Simple Goitre:
- Thyroxin function is low
- Weight gain
- Thick skin
- Sleepiness
- Coarse voice
- Constipation.
describe toxic goiter
Hyper functioning of the thyroid gland • Weight loss • Anxiety • Lack of sleep, • Fine tremors of fingers • Bulging eyes (Exophthalmos) • Diarrhoea
describe cretinism
Deficiency of Iodine in newborns
may lead to hypothyroidism
which may cause problems
with brain growth.
what is RDA of selenium
• Upper level for adults: 400 g/day
what are the sources of selenium
Seafood, meat
• Whole grains
• Vegetables
what are the functions of selenium
Acts as co-factor of glutathione (an antioxidant tripeptide).
• Defends against oxidation (antioxidant role).
• Regulates thyroid hormone
describe role of selenium as antioxidant
Helps in lowering oxidative stress
in the body, which reduces
inflammation and enhances
immunity
describe deficiency of selenium
• Predisposition to heart disease characterized by cardiac tissue
becoming fibrous.
describe toxicity of selenium
Loss and brittleness of hair and nails
• Skin rash, fatigue, irritability, and nervous system disorders
• Garlic breath odor
what is the RDA of fluoride
Men: 3.8 mg/day.
• Women: 3.1 mg/day.
• Upper level for adults: 10 mg/day
what are chief functions of fluoride
- Involved in the formation of bones and teeth.
* Helps to make teeth resistant to decay
sources of flouride
- Drinking water (if fluoride containing or fluoridated).
* Tea, seafoo
describe deficiency of fluoride
• Susceptibility to tooth decay.
what are symptoms of fluoride toxicity
Fluorosis (pitting and discoloration of teeth).
what is RDA manganese
- Men: 2.3 mg/day
- Women: 1.8 mg/day
- Upper level for adults: 11 mg/day
what are the sources of manganese
Nuts
• Whole grains
• Leafy vegetables
what are the functions of manganese
: cofactor for many enzymes that metabolize carbohydates,
lipids and amino acids
what is the RDA of chromium
Men: 35 g/day.
• Women: 25 g/day.
what is the function of chromium
• Enhances insulin action.
what are sources of chromium
Meats (especially liver).
• Whole grains, brewer’s yeast
what are symptoms of chromium deficiency
Diabetes-like condition
what is RDA of molybdenum
for adults: 45 g/day.
• Upper level for adults: 2 mg/day.
what are sources of molybdenum
- Legumes, cereals.
- Organ meats.
- Reproductive effects in animals
what is the function of molybdenum
• Cofactor for several enzymes e.g. xanthine oxidase
