Circadian Rhythm

   

      We all make timetable for our work, and we work on that perfect clock time. As the same our body also have a clock known as biological clock and that biological clock produce a circadian rhythm and regulate their timing.

Circadian rhythm:

Circadian rhythm is known as internal clocks that is present within human beings. These internal clocks control our sleep - wake rhythm/cycle. It also controls our metabolism, body temperature, cognition and many more things. There are many factors that regulate and control of circadian rhythm like light, darkness, and aging. Brain has great role in controlling the cycle.
To know more about circadian rhythms

Let's jump little deeper:

In 2017 three scientist name Jeffrey C Hall, Michael Rosbach and Michael young discovered the molecular mechanism of circadian rhythm and they get physiology Nobel Prize 2017.

  These three-scientist discovered that the circadian rhythm is regulated by the period gene which undergoes its oscillation. The PER protein facilitates the oscillation cycle.  These per protein is present in eye tissue, ovaries, brain neurons and in salivary gland. Scientist found that this PER protein work with TIMELESS gene and that gene code for TIM protein. These per protein work as shuttle between cytoplasm and nucleus and that regulates/maintain the level of PER mRNA.

MASTER CLOCK:

Circadian rhythm is related to our brain, and it is called master clock. In human, master clock is a bunch of 20000 neurons that creates a structure called SCN (suprachiasmatic nucleus) these SCN is present in hypothalamus and receives direct light from the eyes.

    Regulation of timing that is circadian rhythm determines our sleeping pattern. Melatonin is a hormone that are responsible for sleep, and the production of melatonin is regulates by SCN that is our master clock.
Circadian rhythm has two clocks, one is central clock that is located in the SCN and other is peripheral clock that is located in all tissue and organ.

  

Role of light:

When light comes from optic nerve from else to the brain the SCN indicated or stimulates the brain for the production of more melatonin. And thats the reason why people get drowsy. These happen like vice-versa when there is lighter. 

Effect of night shift work: 

Rhythm is disturbed by night shift work and may lead to specific diabetes and cancer. Not only night work but the blue light that comes from your laptop or mobile also disrupt the rhythm by suppressing the production of hormone melatonin by prolong release of PER protein.

Jet lag:

Disruption of circadian rhythm due to traveling to the different time zone is known as jet lag. (scientific term: Circadian dysrhythmia) for jet lag disorder there is no need of any medical treatment because it is a temporary disorder.  Not only light but physical activity also influence of circadian clock. Exercise can improve or reduce the risk of Disruption of circadian rhythmicity. But further research still needs to know the depth of these all reasons.

I Hope you liked it, Thank you :)

@Maulik Ramanandi.

G- PROTEIN COUPLED RECEPTOR

What is GPCR?

A large family of cell surface receptor that send signal to the intracellular targets by the help of intermediatory action of guanine-binding protein called G protein. 

GPCR Stands for G protein coupled receptor or G protein linked receptor. However, G protein binds to the GPCR receptor and stimulates the signal transduction Hence they are to be known as GPCR.

The GPCR signal transduction is based on three essential components; A seven transmembrane helical domain proteins that is associated with plasma membrane, an effector protein that generates an intracellular secondary messenger and A guanine binding protein that activate effector proteins.

What is G protein?

A family of guanine-binding protein that acts as molecular switches inside the cells are involved in transmitting the signal from outside the cell to inside the cell.

Without G protein, the seven membrane helices cannot produce signals.

What is stimulating G protein?

When G proteins involve in the activation of enzymes like effector adenylate cyclase is called stimulating G protein(Gs)

What is primary messenger?

Primary messengers are basically a ligand that interacts with the surface of receptors firstly such as neurotransmitters, Growth stimulating hormones, Nitric oxides etc.

What is Secondary messenger?

Secondary messengers are signal molecules that is produce when stimulatory G protein interacts with effector proteins like adenylyl cyclase. Secondary messengers are. 

• Cyclic adenosine monophosphate (cAMP)
• Cyclic guanosine monophosphate (cGMP)
• Inositol triphosphate (IP3) 
• Diacylglyceral (DAG) 

The removal and degradation of secondary messenger terminate cellular response.

GPCR signal transduction was discovered and explored by Nobel laureates ALFRED G. GILMAN and MARTIN RODBELL. They discovered β-adrenergic(epinephrine) receptor system.

How GPCR signal transduction works?

The GPCR has seven membrane helices domains that is known as serpentine receptor or hepta-helical receptor. It is transmembrane proteins with seven hydrophobic regions residue that is snakelike heads and tails across the plasma membrane. The outside of PM is -NH2 region and inside the PM is -COOH region. 

The ligand like neurotransmitters bind to the surface of the receptor of GPCR within the PM. see figure (a).

Transduction of epinephrine signal:the β-adrenergic pathway. (Pic: principle of biochemistry by leninger)

STEPS:

• It promotes the confirmational change in the receptor's intracellular domain.
• The stimulating G protein (Gs) is heterotrimeric protein with subunits α, β γ. The Gs is bounded with GDP then it doesn't produce secondary signal. Hence in this case it is off. While GTP replaces GDP and α subunit of Gs binds with effector proteins then it became active and produce secondary messenger. The βγ subunits dissociate from and go further for new.

• α subunits of Gs associate with the effector protein (Adenylyl cyclase) and activate it.
• The Cyclic adenosine monophosphate (cAMP) activates protein kinase A.
• This protein kinase A phosphorylate cellular protein and produce cellular response to the cell.

When cAMP degrade it terminate cellular response.

Posted by Bharrat Bhassker.

β-Oxidation of saturated fatty acid

β-oxidation:

β-oxidation is the removal of successive two-Carbon atoms from the Carboxyl(-COOH) end of the Fatty Acyl Chain to form two carbons containing acetyl coA.

For example, the 16-carbon containing Palmitic acid undergoes seven β-oxidation process and in each oxidative process they lose two carbons containing Acetyl CoA. Thus, the overall conversion of 16-carbon containing Palmitic acid in seven cycle produces total 8-Acetyl coA. See figure-1 (b).   

β-oxidation takes place in mitochondria in eukaryotes and in cytosol in prokaryotes.

β-oxidation mechanism was explained by Franz Knoop in 1904. Knoop experimented on the dog he fed the long chain of linear fatty acid in which a phenyl chain attached at ω-Carbon of fatty acid.
They found that the urine of dog contains derivative of phenyl acetate when they were fed by phenylbutyrate (even noₛ of carbons).

Again, when dogs are fed by phenyl propionate (odd noₛ of carbons), the derivative of benzoate were formed. In both case two carbon molecule is cleaved from the fatty acids. Thus, Knoop hypothesized from these experiments that fatty acids are degraded by oxidation at β-carbon i.e fatty acid degrades into two-carbon units this is known as Knoop's hypothesis(β-oxidation).

The β-oxidation of Saturated fatty acid has basically four steps mechanism which is illustrated in figure.1(a).

First step: α,β-Dehydrogenation of acyl CoA

In this step, palmitoyl-CoA (Acyl CoA) is oxidized by an enzyme called acyl CoA dehydrogenase and produces trans-Δ²-enoyl CoA (Δ² symbolises the position of double bond) which having trans double bonds between α and β carbon atoms (C₂ and C₃).

N.B:  Note that the double bond in enoyl coA has trans configuration whereas the double bond in natural occurring unsaturated fatty acid are normally in cis configuration.

The first step is catalysed by three isozymes (same enzymes, same catalytic activity but differ in amino acid sequences) of Acyl-CoA dehydrogenase which is present in matrix of Mitochondria. Each Acyl-CoA dehydrogenase work specifically on specific range of fatty acyl chain. Acyl-CoA dehydrogenase is analogous to succinate dehydrogenase in the citric acid cycle.

(a) SCAD (short chain Acyl-CoA dehydrogenase)-acts on fatty acid of C₄ to C₆ carbons.

(b)MCAD (Medium chain Acyl-CoA dehydrogenase)- acts on fatty acid of C₆ to C₁₄ carbons.

(c)VLCAD (very long chain Acyl-CoA dehydrogenase)-acts on fatty acid of C₁₄ to C₁₈ carbons.

All three isoenzymes are flavoprotein which contain FAD as prosthetic group.

FAD acts as electron acceptor which accept electrons when electrons are removed from fatty acyl-CoA.

(a)

(b)

Figure-1: β-oxidation cycle (a) In each pass through this four-step sequence, one acetyl residue (shaded in Green) is removed in the form of acetyl-CoA from the carboxyl end of the fatty acyl chain —in this example palmitate(C₁₆), which enters as palmitoyl-CoA. (b) 6 more molecule of acyl CoA passes through to the β- oxidation pathway yield 7 more molecules of acetyl-CoA. The seventh arising from the last two carbon atoms of the 16-carbon chain, total eight molecules of of acetyl-CoA formed.

Second step: Hydration of α-,β-acyl CoA

 In the second step, water is added to the double bond of enoyl-Δ²-CoA to form the L-stereoisomer of β-hydroxacyl-CoA(3-hydroxyacyl-CoA) by the help of enoyl-CoA hydratase. It is analogous to fumarase enzyme of citric acid cycle.

Third step: Oxidation of β-hydroxyacyl CoA

In the third step,β-hydroxyacyl CoA is dehydrogenated by the help of β-hydroxyacyl CoA dehydrogenase to form β-ketoacyl CoA. NAD+ is the electron carrier molecule. This enzyme is closely analogous to malate dehydrogenase of citric acid cycle.

Fourth step: Thiolysis of β-ketoacyl CoA

The last step is catalysed by thiol(-SH) group of enzyme Acyl-CoA acetyltransferase, also known as thiolase, it promotes thiolysis of β-ketoacyl-CoA. The thiolase enzyme cleave β-ketoacyl-CoA at C₂ and C₃ carbons. Hence their end products are acetyl CoA that is first two carbon (C₁ and C²) containing original molecule and the another is acyl CoA chains which is less than two carbon undergo again in the β-oxidation cycle.


Posted by Bharrat Bhassker.

Amino Acids and it's classification

Amino acid:

An amino acid is the basic molecule of proteins. It is structural and functional unit of proteins. It has four different functional  groups attached to the central carbon atom. It general structure contains one carboxyl group(-COOH), one amino group(-NH2), one alkyl group(-R) and one Hydrogen atom.

General structure:

Note: Alkyl group of amino acid either may have aliphatic or aromatic chains.
[e.g-alanine(CH3-as R-groups),Phenylalanine(CH3+Benzene ring)]

There are total 20 common amino acids that encodes for protein synthesis. (Exception: Selenocysteine -21st Amino acid is derivative of cysteine contains selenium rather than sulfur. While pyrrolysine -22nd amino acid that means lysine contains pyrrole ring.

Classification of Amino acid:

Amino acid can be classified based on their:

(I) Location of amino group (-NH2).
(II) Polarity
(III) Nutritional value
(IV) Metabolic rate
(V) structure

(I) Based on the location of amino group(-NH2)

(II)Based on Polarity : 

A.A classified into 4
different categories.
(a) Nonpolar A.A.
(b) Polar A.A with No charge on R-groups.
(c) Polar A.A with +ve R groups.
(d) Polar A.A with -ve R groups.

              (a)Nonpolar Amino acid

	Non Polar A.A
Aliphatic R Groups		Aromatic R Groups
Glycine (G)		Phenylalanine (F)
Alanine (A)		Tryptophan (W)
Valine (V)
Leucine (L)
Isoleucine (I)
Proline (P)
Methionine (M)

             (b) Polar A.A with No charge on R groups

Sr. NO:	Amino Acid
1	Glycine (G)
2	Serine (S)
3	Threonine (T)
4	Cysteine (C)
5	Tryptophan (W)
6	Asparagine (N)
7	Glutamine(Q)
8	Tyrosine (Y)
Mnemonics	whY GST Comes Without Notice ?(Question mark)

            

 (c) Polar with +R groups

Sr. NO:	Amino Acid
1	Lysine(K)
2	Arginine(R)
3	Histidine(H)

             

(d) Polar with -R groups

Sr. NO:	Amino Acid
1	Proline (P)
2	Aspartic Acid(D)

(III)Based on Nutritional Value
     (a) Essential: A.A that cannot be systhesize by our body, only taken as diets.

     (b)Semi-essential: A.A that can synthesize in adults but not in growing children.

      (c) Non-essential: A.A that can synthesize in our body and doesn't require to take from outside as in diets.

	Based on Nutritional Value
Essential A.A	Semi- Essential A.A	Non-Essential A.A
Methionine (M)	Histidine (H)	Glycine (G)
Phenylalanine (F)	Arginine (R)	Alanine (A)
Isoleucine (I)		Proline (P)
Lysine (K)		Serine (S)
Leucine (L)		Cysteine (C)
Valine (V)		Aspartic Acid (D)
Tyrosine (Y)		Glutamic Acid (E)
Threonine (T)		Glutamine (Q)
Tryptophan (W)		Asparagine (N)

(IV) Based on Metabolic Rate
   (a)Glycogenic A.A: Precursor for the formation of glucose or glycon.

   (b) Ketogenic A.A: Fats can be synthesized from these amino acids and it's precursor.

   (c) Glycogenic & Ketogenic A.A:  Four A.A are precursor for the synthesis of glucose and fats.

	Based on Metabolic Rate
Gluconic A.A	Ketonic A.A	Gluconic & Ketonic A.A
Glycine (G)	Lysine (K)	Isoleucine (I)
Alanine (A)	Leucine (L)	Phenylalanine (F)
Methionine (M)		Tryptophan (W)
Aspartic Acid (D)		Tyrosine (Y)
Mnemonics: GAMD	Mnemonics: KL-Rahul	Mnemonics: WIFY

(V) Based on Structure 

   (a) A.A with Aliphatic side chain

Sr. NO:	Amino Acid
1	Glycine (G)
2	Alanine (A)
3	Valine (V)
4	Leucine (L)
5	Isoleucine (I)

      

(b) A.A containing -OH groups.

Sr. NO:	Amino Acid
1	Threonine (T)
2	Serine (S)
3	Tyrosine (Y)

      

(c) A.A containing Sulfur groups

Sr. NO:	Amino Acid
1	Methionine (M)
2	Cysteine (C)
3	Cystine

       

 (d) Acidic A.A with their amides 

Sr. NO:	Amino Acid
1	Aspartic Acid(D)
2	Glutamic Acid (E)
3	Asparagine (N)
4	Glutamine(Q)

      

   (e) Basic A.A

Sr. NO:	Amino Acid
1	Lysine(K)
2	Arginine(R)
3	Histidine(H)

      

   (f) Aromatic A.A

Sr. NO:	Amino Acid
1	Phenylalanine (F)
2	Tyrosine (Y)
3	Tryptophan (F)

   (g) Imino group A.A

Sr. NO:	Amino Acid
1	Proline (P)

Posted and created by @Bharrat 

Bhassker

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