Transcript متابوليسم چربيها

‫متابولیسم چربیها‬
Introduction
Cholesterol
Phospholipid
Triglycerides Bile Salts T G Emulsion Lipase
Fatty acids +Monoglycrid+Diglycrid
<10 carbone
Absorbed
> 10 C in Intestine Cells with cholesterol
&phspholipid &M.G &D.G& Protein
Chylomicrones
Breakdown of Triacylglycerols
The lipases break the
triacylglycerols down to
fatty acids and glycerol
The fatty acids are
transportred in the blood by
serum albumin
Transport into Mitochondrial Matrix
Acyl-CoA Synthetase
Fatty acid oxidation
Acyl-CoA Synthetase
‫‪ATP Yield‬‬
‫درهرمرحله یک ‪FADH2‬تولید میشودکه در زنجیر انتقال الکترون ‪2ATP‬میدهد ‪.‬‬
‫درهرمرحله یک ‪NADH2‬تولید میشودکه در زنجیر انتقال الکترون ‪3ATP‬مدهید‪.‬‬
‫درهرمرحله یک استیل کوآنزیم آ تولید میشودکه در سیکل کربس ‪12ATP‬میدهد‪.‬‬
‫پس در هر مرحله بتااکسیداسیون ‪17ATP‬تولید میشود‪.‬‬
‫اگر اسید چرب ‪ 2n‬کربن در ساختمان آن باشد واکنشهای بتا اکسیداسیون ‪n-1‬مرتبه‬
‫تکرار میشود‪ .‬بنابراین خواهیم داشت‪.‬‬
‫چون در پایان دو استیل کوآداریم ودومی ‪ 12ATP‬تولید میکند‬
‫‪ATP=17(n-1)+12‬‬
‫وچون در ابتدا ‪2ATP‬مصرف شد ‪.‬بنابراین‪:‬‬
‫‪ATP=17(n-1)+10‬‬
‫‪ATP=17n – 7‬‬
‫اگر تعداد کربن اسید چرب فرد باشد ‪3 .‬کربن ازاسید چرب کم کرده وطبق باال عمل نموده ودر‬
‫پایان ‪6ATP‬به آن اضافه میکنیم‪.‬‬
‫اگر تعداد کربن اسید چرب فرد باشد ‪3 .‬کربن ازاسید چرب کم کرده ازرابطه زیر استفاده میکنیم‬
‫‪ATP= 17n-1‬‬
‫‪.‬‬
‫(جدید)محاسبه انرژی سوختن چربیها‬
‫درهرمرحله یک ‪FADH2‬تولید میشودکه در زنجیر انتقال الکترون‬
‫‪ATP1/5‬میدهد ‪.‬‬
‫درهرمرحله یک ‪NADH2‬تولید میشودکه در زنجیر انتقال الکترون‬
‫‪ATP2/5‬مدهید‪.‬‬
‫درهرمرحله یک استیل کوآنزیم آ تولید میشودکه در سیکل کربس‬
‫‪ATP10‬میدهد‪.‬‬
‫پس در هر مرحله بتااکسیداسیون ‪ATP 14‬تولید میشود‪.‬‬
‫اگر اسید چرب ‪ 2n‬کربن در ساختمان آن باشد واکنشهای بتا اکسیداسیون ‪n-‬‬
‫‪1‬مرتبه تکرار میشود‪ .‬بنابراین خواهیم داشت‪.‬‬
‫چون در پایان دو استیل کوآداریم ودومی ‪ ATP10‬تولید میکند‬
‫‪ATP=14(n-1)+10‬‬
‫وچون در ابتدا ‪2ATP‬مصرف شد ‪.‬بنابراین‪:‬‬
‫‪ATP=14(n-1)+8‬‬
‫‪ATP=14n – 6‬‬
‫اگر تعداد کربن اسید چرب فرد باشد ‪3 .‬کربن ازاسید چرب کم کرده وطبق باال عمل‬
‫نموده ودر پایان ‪5ATP‬به آن اضافه میکنیم‪.‬‬
‫اگر تعداد کربن اسید چرب فرد باشد ‪3 .‬کربن ازاسید چرب کم کرده ازرابطه زیر‬
‫‪ATP= 14n-1‬‬
‫استفاده میکنیم ‪.‬‬
Ketone Bodies
Use of fatty acids in the citric acid cycle
requires carbohydrates for the the
production of oxaloacetate.
During starvation or diabetes, OAA is used to
make glucose
Fatty acids are then used to make ketone bodies
(acetoacetate and D–3–hydroxybutarate)
‫ترکیبات ستونی‬
‫‪-1‬استو استیک اسید‪.‬‬
‫‪ -2‬بتا هیدرکسی بوتیریک اسید‪.‬‬
‫‪ -3‬استون‬
‫هرگاه اختاللی در متابولیسم کربوئیدراتها‬
‫ایجاد شود استیل کوآ حاصل از سوختن‬
‫چربیها چون نمی تواند وارد سیکل‬
‫کربس شود جمع میشود وبا همدیگر‬
‫ترکیب وتولید ترکیبات ستونی میکند‪.‬‬
‫مواقع ایجاد؟‬
‫‪ -1‬در قحطی ها وگرسنگی های شدید‪.‬‬
‫‪ -2‬در دیابت‬
‫‪-3‬‬
‫‪-4‬‬
Fatty Acid Synthesis.
Fatty acid are synthesized and degraded by
different pathways.
Synthesis takes place in the cytosol.
Intermediates are attached to the acyl carrier
protein (ACP).
In higher organisms, the active sites for the
synthesis reactions are all on the same
polypeptide.
The activated donor in the synthesis is malonyl–
ACP.
Fatty acid reduction uses NADPH + H+.
Elongation stops at C16 (palmitic acid)
‫بیو سنتز‬
‫اسید‬
‫های‬
‫چرب‬
Acyl Carrier Protein
The intermediates in fatty acid synthesis are
covalently linked to the acyl carrier protein
(ACP)
Citrate Shuttle
Acetyl–CoA is synthesized in the
mitochondrial matrix, whereas fatty acids
are synthesized in the cytosol
Acetyl–CoA units are shuttled out of the mitochondrial matrix as citrate:
Eicosanoid Hormones
Eicosanoid horomones are synthesized from
arachadonic acid (20:4).
Prostaglandins
20-carbon fatty acid containing 5-carbon ring
Prostacyclins
Thromboxanes
Leukotrienes
contain three conjugated double bonds
6.2 Eicosanoid Hormones
Cholesterol: What is it?
Cholesterol is a fatty steroid made primarily in
the liver of most animals and humans. It is an
integral component in the synthesis of
hormones, can also be found in cell walls of
animals and humans.
Isolated cholesterol is a white, flaky solid that is
insoluble in aqueous environments.
Cholesterol
H O
‫بیو سنتز کلسترول‬
‫‪-‬‬
‫بیو سنتز‬
‫‪statin drugs&Cholesterol‬‬
‫کلسترول‬
‫دفع کلسترول‬
cholesterol.
‫متابولیسم پروتئین ها‬
‫و‬
‫اسیدهای امینه‬
Dietary protein
Pepsin
Polypeptide Mixture
Trypsin,
Chymotrypsin
carboxypeptid
ase
Aminopeptidase
Tripeptidase
dipeptidase
Non Protein Nitrogen (NPN)
‫انواع پروتئین های بافتی‬
‫سنتز‬
‫تجزیه‬
Aminoacid
Deamination
Aminoacid &
oligopepti
Blood
Aminoacid
R-CH-COOH
NH2
Liver
NH3
Urea
‫کتو اسید‬
Kidney
ATP
‫سیکل کربس‬
NH4
Urine
‫متابولیسم اسیدهای آمینه‬
‫اسیدهای امینه ازسه طریق وارد چرخه متابولیسم میشوند‪:‬‬
‫‪ -1‬ازطریق غذا‪ -2 .‬ازطریق انحالل پروتئینها‪ -3 .‬سنتز در‬
‫بدن‬
‫واکنشهای اسید های آمینه‪:‬‬
‫‪ -1‬واکنشهای عمومی شامل دآمینه و دکربوکسیله‪.‬‬
‫‪ – 2‬سرنوشت عامل آمین‪.‬‬
‫‪ – 3‬سرنوشت ریشه کربنی اسید آمینه‪.‬‬
‫دآمینه شدن‬Deamination
1-Transaminases: I(AST) aspartate
aminotransferase Serum
Glutamate:oxaloacetate
transaminase [SGOT]
COO
COO
COO
CH2
COO
CH2
CH2
CH2
CH2
CH2
HC
NH3+
+
COO
C
O

COOPyridoxal
phosphate
(PLP)-
C
O
+
COO
HC
NH3+
COO
aspartate -ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
II-Serum
Glutamate:pyruvate
transaminase [SGPT]
alanine
aminotransferase
(ALT)
CH3
HC
COO
COO
CH2
CH2
CH2
NH3+
COO
+
C
CH3
O
COO phosphate
Pyridoxal
C
CH2
O
COO
+
HC
NH3+
COO
(PLP)-
alanine
-ketoglutarate
pyruvate
glutamate
Aminotransferase (Transaminase)
‫دآمینه شدن‬Deamination
2-Glutamate dehydrogenase [GluDH]
‫دآمینه شدن‬Deamination
3- L –amioacid oxidase :
R-CH –COOH
NH2
H2O
R-CO-COOH
NH3
‫دآمینه شدن‬Deamination
Non Oxidativ Deamination
‫دآمینه شدن غیر اکسیاتیو‬
glutaminase
glutamine + H2O
glutamate + NH3
Aspargine +H20
Asparginase
Asparticacid + NH3
Serine Dehydratase catalyzes: serine  pyruvate + NH3
‫سرنوشت عامل آمین‬
.
‫سرنوشت ریشه کربنی‬
‫اسید های امینه ای که ریشه کربنی آنها تبدیل به اسید پیرویک یا یکی‬
‫از واسطه های سیکل کربس شود به آنها اسید های امینه گلیکوژنیک‬
‫یا قند ساز میگویند‪.‬‬
‫اسید های امینه ای که ریشه کربنی آنها تبدیل به استیل کوا یا‬
‫استواستیل کوا شود به آنها اسید های امینه کتوژنیک یاستون ساز‬
‫میگویند‪.‬‬
Glucose
Phosphoenolpyruvate
Glycine
Cysteine
Serine
Alanine
Threonine
Tryptophan
Isoleucine
Leucine
Leucine
Lysine
Phenylalanine
Tyrosine
Tryptophan
Pyruvate
Asparagine
Aspartate
Tyrosine
Phenylalanine
Isoleucine
Valine
Methionine
Threonine
Acetyl CoA
Acetoacetyl CoA
Oxaloacetate
Fumarate
Succinyl
CoA
Citrate
-ketoglutarate
Glutamate
Glutamine
Histidine
Proline
Arginine
Fates of the carbon skeletons of amino acids. Glucogenic amino acids are
shaded red, ketogenic amino acids are shaded green and glucoketogenic
32
amino acids are shaded blue.
Histidine Metabolism:
Histamine Formation
H
N
+
NH 3
CH 2CHCO 2-
Histidine
decarboxylase
H
N
CH 2CH 2NH 2
N
Histidine
CO2
N
Histamine
Histamine:
• Synthesized in and released by mast cells
• Mediator of allergic response: vasodilation, bronchoconstriction
(H1 receptors)
• H1 blockers: Diphenhydramine (Benadryl)
Loratidine (Claritin)
• Stimulates secretion of gastric acid (H2 receptors)
• H2 blockers: Cimetidine (Tagamet); ranitidine (Zantac)
HO
HO
‫متابولیسم فنیل آالنین و تیروزین‬
‫فنیل کتون ها‬
‫سنتز انواع پروتئینها بافتی‬
NH 3+ Phenylalanine
(Essential)
CH 2CHCO 2-
(Phenylalanine
Phenylketonuria (PKU) Disease
‫سنتز انواع پروتئینها بافتی‬
hydroxylase)
HO
Tyrosine
NH 3+
NH 3 +
DOPA
CH 2 CHCO 2
CH 2CHCO 2 -
-
‫ ید‬+
T3& T4
Tyrosine
Tyrosinase
NADPH + H+
Albinism
Epinephrine
(Adrenaline)
‫تیروئید‬
Melanine
)‫الکاپتون‬Homogentisate
Alkaptonuria ×
Norepinephrine
Homogentisate
dioxygenase
Fumarate + acetoacetate
ATP
‫سیکل کربس‬
Catecholamine Biosynthesis
HO
HO
NH 3
Tyr hydroxylase
+
NH 3+
CH 2CHCO 2 -
O2
HO
CH 2CHCO 2 -
HO
Tyrosine
HO
Catechol
Dihydroxyphenylalanine
(DOPA)
DOPA
decarboxylase
Epinephrine
(Adrenaline)
CHCH 2NHCH 3
OH
Methyl
transferase
S-Adenosylhomocysteine
Dopamine
hydroxylase
HO
CH 2CH 2NH 2
HO
HO
CO2
Dopamine
SAM
HO
DOPA, dopamine, norepinephrine,
and epinephrine are all neurotransmitters
CHCH 2NH 2
OH
Norepinephrine
35
L-DOPA in Parkinsonism
Blood
Brain
L-DOPA
L-DOPA
Dopamine
HO
CH 3
HO
Blocks
CH 2 -C-CO 2 H
Carbidopa
NHNH 2
Dopamine
Blood
Parkinsonism associated with
dopamine in brain through loss of
neurons in basal ganglia.
Carbidopa + L-DOPA
Brain Barrier
36
Monoamine Oxidase (MAO)
HO
HO
MAO
(in mitochondria)
CHCH 2NHR'
HO
HO
R
R
R’
OH H
Norepi
OH CH3 Epi
H
H
Dopamine
R
Aldehyde
dehydrogenase
HO
HO
MAO inhibitors (e.g., tranylcypromine) are useful
in the treatment of depression
Brain levels of dopamine and norepi.; also
serotonin
CHCHO
CHCO 2H
Urinary R
metabolite
R=OH Vanillylmandelic acid (VMA)
R=H Homovanillic acid (HVA)
37
Tyramine
OH
MAO
CH 2 CH 2 NH 2
OH
CH 2CHO
Tyramine
( blood pressure)
• Tyramine found naturally in several types of cheese;
also beer and red wine.
• Tyramine intake can cause hypertensive crisis in
persons taking a MAO inhibitor ( norepi release)
38
Catechol-O-Methyl Transferase
(COMT)
HO
HO
HO
COMT
CHCH 2NHR'
Active
catecholamine
R
CHCH 2 NHR'
CH 3 O
SAM
S-Adenosylhomocysteine
R
Inactive
metabolite
• COMT found in cytoplasm
• Terminates activity of catecholamines
• Catecholamine excretion products result from
combined actions of MAO and COMT
• Inhibitors of COMT (e.g., tolcapone) useful
in Parkinson’s disease
39
Melanin Formation
HO
Tyr hydroxylase
NH 3+
CH 2CHCO 2 -
HO
NH 3+
O2
Tyrosine
CH 2CHCO 2 -
HO
DOPA
Tyrosinase
O
Melanin
(Black polymer)
Highly colored
polymeric
intermediates
O
Melanin formed in skin (melanocytes), eyes, and hair
In skin, protects against sunlight
Albinism: genetic deficiency of tyrosinase
CH 2CHCO 2+
NH 3
Dopaquinone
40
+
NH 3
Indole ring
+
NH 3
CH 2 CHCO 2 -
Trp
hydroxylase HO
CH 2 CH 2 NH 2
CH 2 CHCO 2 -
HO
Decarboxylase
N
H
O2
5-Hydroxytryptophan
Tryptophan
(Trp)
N
H
N
H
CO2
MAO
5-Hydroxytryptamine (5-HT);
Serotonin
CH 2CHO
HO
N
H
Dehydrogenase
CH 2 CO 2H
CO 2H
B3
HO
N
H
N
5-Hydroxyindole acetic
acid (5-HIAA) (Urine)
Amino Acids Formed From Ketoglutarate
O
O 2 CCH 2 CH 2 CCO
-Ketoglutarate
2
-
4 Steps
Transamination or
Glutamate
dehydrogenase
CO 2-
+
N
NH3+
-
O 2 CCH 2 CH 2 CHCO 2
-
Glutamate
Glutamine
synthase
O
H
5 Steps
Glutamine
Proline
NH3+
+
H3 NCH 2 CH 2 CH 2 CHCO 2 - Ornithine
Urea Cycle
NH3+
H2 NCCH 2 CH2 CHCO 2 -
H
NH 2
NH 3+
+
H2 N=C-HN CH 2 CH 2 CH 2 CHCO
Guanidino group
2
-
42
Arginine
Synthesis of Nitric Oxide
NH 2
NH 3+
+
H2 N=C-HN CH 2 CH 2 CH 2 CHCO
Arginine
2
-
Nitric oxide synthase (NOS)
NH 3+
NH 2 CONH CH 2 CH 2 CH 2 CHCO
2
-
+
NO
Citrulline
43
Nitric Oxide
• Cell messenger
• Implicated in a wide range of physiological
and pathophysiological events:
• Vasodilation:
• Activates guanylyl cyclase cGMP
• Nitroglycerin
Glycerin + NO
• Sildenafil (Viagra): in vascular smooth muscle:
NO
Blocks
cGMP
Phosphodiesterase-5
GMP
44
Formation of Serine
CO 2 -
Glucose
Glycolysis
Dehydrogenase
H C OH
NAD+
CH 2 OPO 3-2
3 Steps
NADH +
H+
3-Phosphoglycerate
Pyruvate
C=O
CH 2 OPO 3-2
3-Phosphohydroxypyruvate
Inhibits
CO 2
CO 2 -
Glutamate
Transaminase
-Ketoglutarate
-
CO 2 -
Phosphatase
H C NH 3 +
CH 2 OH
Serine (Ser)
H C NH 3 +
CH 2 OPO 3-2
3-Phosphoserine
45
Conversion of Serine to Glycine
H
Dihydrofolate
reductase
Folate
H2 N
N
N
CO 2 -
N
N
OH
CH2 NHR
H C NH 3 +
H
Tetrahydrofolate
(FH4)
CH 2 OH
Serine hydroxymethyl
transferase (PLP-dep.)
H
N
Key intermediate
in biosynthesis of
purines and
formation of
thymine
Serine
CO 2 N
Glycine
CH2
H C NH 3 +
N
H
H2C
N5,
N10-Methylene
FH4
Important in
biosynthesis of heme,
porphyrins, and purines
46
Sulfur-Containing Amino Acids
NH 3
Methionine
Synthase
(Vit. B12-dep.)
+
CH 3SCH 2CH 2CHCO
Methionine
(Essential)
- + FH4
2
NH 3+
HS CH 2CH 2CHCO 2 + 5-Methyl
L-Homocysteine
CO 2 -
Cystathionine
b-synthase
(PLP-dep.)
NH 3+
OH
-
CH 3CHCH 2CO 2
b-Hydroxybutyrate
FH4
Cystathionine
lyase
+ HS CH 2CHCO 2Cysteine
(Non-essential)
H C NH 3 +
Serine
CH 2 OH
NH 3+
-
SCH 2CH 2CHCO 2
CH 2CHCO 2NH 3
+
Cystathionine
47
Homocysteine
Homocysteinuria
• Rare; deficiency of cystathionine b-synthase
• Dislocated optical lenses
• Mental retardation
• Osteoporosis
• Cardiovascular disease
death
High blood levels of homocysteine associated with
cardiovascular disease
• May be related to dietary folate deficiency
• Folate enhances conversion of
homocysteine to methionine
48
Methionine Metabolism: Methyl Donation
NH 2
N
N
NH 3+
CH 3SCH 2CH 2CHCO
2
S-Adenosyl methionine
synthase
-O
+
2 CCHCH 2 CH 2 -S-H2 C
NH 3 +
ATP
Methionine
N
+
H3 NCH 2 CH 2CH 2-S-H 2C
+
CO2
CH 3
OH OH
N
N
-O
O
S-Adenosyl
Methionine
(SAM)
N
N
N
N
CH 3
NH 2
NH 2
N
O
OH OH
SAM
Decarboxylase
Decarboxylated
SAM
N
N
2 CCHCH 2 CH 2 -S-H2 C
O
Methyltransferases
R-CH3
NH 3 +
S-Adenosyl
homocysteine
R-H
OH OH
49
Polyamines
•
Spermidine and spermine found in virtually
all procaryotic and eucaryotic cells
• Precise role undefined
• Bind to nucleic acids
• Inhibition of biosynthetic pathway:
CO 2H
NH 2
H2N
CHF 2
-Difluoromethylornithine (DFMO)
(Eflornithine) - inhibits ODC;
used to treat
Pneumocystis carinii infectons
50
Polyamine Biosynthesis
NH3+
+
H3 NCH 2 CH 2 CH 2 CHCO 2 Ornithine
(from urea cycle)
Ornithine
decarboxylase
(ODC)
(PLP-dep.)
+
H3N
Putrescine
CO2
Decarboxylated
SAM
Spermidine
synthase
H
+
H3N
N+
+
N
H
H
+
NH 3
+
NH 3
Spermine
synthase
H
Spermine
5’-Methylthioadenosine
Decarboxylated
SAM
+
H3N
5’-Methylthioadenosine
H
+N
H
+
NH 3
Spermidine
51
Creatine and Creatinine
NH 2
Arginine-glycine
transamidinase
(Kidney)
+
NH 3
+
H2 N=C-HN CH 2 CH 2 CH 2 CHCO
2
NH 2
+
H2 N=C-HN CH 2 CO 2 -
-
Glycine
Arginine
Ornithine
Guanidoacetate
SAM + ATP
H
N
Creatinine HN
(Urine)
O
Guanidoacetate
Methyltransferase
(Liver)
Non-enzymatic
(Muscle)
N
CH 3
NH 2
Creatine
Creatine kinase
(Muscle)
+
H2 N=C-N CH 2 CO 2 CH 3
ATP
ADP
+ Pi
S-Adenosylhomocysteine
+ ADP
NHPO 3-2
+
H2 N=C-N CH 2 CO 2 CH 3
Phosphocreatine
52
Creatine and Creatinine
Creatine:
• Dietary supplement
• Used to improve athletic performance
Creatinine:
• Urinary excretion generally constant;
proportional to muscle mass
Creatinine Clearance Test:
• Compares the level of creatinine in urine (24 hrs.)
with the creatinine level in the blood
• Used to assess kidney function
• Important determinant in dosing of several drugs
in patients with impaired renal function
53
‫ساختمان نوکلئوتید ها و‬
‫اسیدهای نوکلئیک‬
‫ساختمان نوکلئوتید ها و اسیدهای نوکلئیک‬
Nucleic Acid Structure
A.
B.
C.
D.
E.
F.
G.
Structure of nucleotides
Nitrogenous bases
Pentose sugars
Nucleosides
Nucleotides
Nucleotide chains
Structure of B-DNA
A. Structure of Nucleotides
• A nucleotide is composed of
A nitrogenous base:Purines:Adenine& Guanine
Pyrimidines:Cytosine &Thymine&Uracil
A pentose sugar
A phosphate group
Nucleosides & Nucleotides
•
•
Base + sugar  nucleoside
Base + sugar + phosphate(s)  nucleotide
• Nucleoside
A pentose sugar molecule with a nitrogenous
base attached to the 1´ carbon
Nucleosides are named by using the root of the
base name, plus the suffix “-osine” (for
purines) or “-idine” (for pyrimidines)
Nucleosides with deoxyribose sugars are
designated with the prefix “deoxy-”
NUCLEIC ACID STRUCTURE
• DNA and RNA are large macromolecules with
several levels of complexity
• Nucleotides form the repeating units
• Phosphodiester bonds link
nucleotides to form a strand
• Two strands interact to form
a double helix
• The double helix interacts with
proteins resulting in 3-D structures
in the form of chromatin
3D structure
Nucleotide Polymerization Reaction:
Phosphodiester Bond Formation
Figure 9.11
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
9-30
Base Pairing Key to DNA Structure
Features of the DNA Double Helix
2 nm
5end
3end
H
H HH
H
P
One complete
turn 3.4 nm
A S
S
P
P
S
G C
P
S
P
5phosphate
S
G C
P S
SC P S
P S
P
S P
S
A T S P
G C S P
S
P
C G S
S P
T A P
S
P S
P
3hydroxyl
P S G
P S
C G P
S
P
T A
S
P
S G C
S
P
One nucleotide
A T
S
0.34 nm
S
P
S
P
P
SC G
S P
S C G
P
N
O
N
O–
H
N
O P O CH2
O
O–
HH
HH
N
O
H
HH
N
H
O
O
N
O
O P O CH2 O
N
NH2
O–
HH
HH
H
H
H
H N
N
H2N
N
N
O H
O
N
O P O CH2 O
N
O
O–
HH
HH
H CH3
OH H
3end
O–
CH2 O P O
O
H
NH22
N NH
N
H
HH
O
N
H2N
HO
HH
O
H
O–
CH2 O P O
O
H
HH
N
N
HH
O
H
O–
CH2 O P O
O–
H2N
5 end
Features of the DNA Double Helix
Minor
groove
Major
groove
Minor
groove
Major
groove
Ball-and-stick model of DNA
Space-filling
model of DNA
‫انواع‪DNA‬‬
‫‪ BDNA :‬‬
‫هلیکس آن راست گرد می باشد‪.‬‬
‫در هر دور آن ‪ 10‬جفت باز وجود دارد‪.‬‬
‫طول هر دور آن ‪ 4/3Å‬می باشد‪.‬‬
‫فاصله دو رشته آن ‪)2 nm ( 20Å‬است‪.‬‬
‫بازها نسبت به محور هلیکس بصورت عمود قرار‬
‫می گیرند‪.‬‬
‫در ساختمان آن ‪ 2‬نوع شیار دیده می شود‪:‬‬
‫‪major grove - minor grove‬‬
‫طول شیار بزرگ ‪)2/2 nm ( 22Å :‬‬
‫طول شیار کوچک ‪)2/1 nm ( 12Å :‬‬
‫انواع‪DNA‬‬
‫‪ ‬در صورت کم بودن رطوبت محیط یا زیاد بودن نمک محیط‬
‫‪ZDNA‬و ‪ ADNA‬بوجود می آیند‪.‬‬
‫‪:ADNA ‬‬
‫هلیکس آن راست گرد می باشد‪.‬‬
‫در هر دور آن ‪ 11‬جفت باز وجود دارد‪.‬‬
‫بازها نسبت به محور هلیکس زاویه ‪ 23‬درجه دارند‪.‬‬
‫در ساختمان آن فقط یک نوع شیار دیده می شود‪.‬‬
‫‪:ZDNA ‬‬
‫هلیکس آن چپ گرد می باشد‪.‬‬
‫در هر دور آن ‪ 12‬جفت باز وجود دارد‪.‬‬
‫بازها نسبت به محور هلیکس زاویه ‪ 180‬درجه دارند‪.‬‬
‫در ساختمان آن فقط یک نوع شیار دیده می شود‪.‬‬
‫‪BDNA‬‬
‫‪ADNA‬‬
Comparison of A, B, and Z forms of
DNA
RNA Structure
• The primary structure of an RNA strand is much
like that of a DNA strand
• RNA is made as a single strand only, however it
may form a double stranded structures
• RNA strands can be a 10s to1000s of nt in length
• RNA is made from a DNA template - only one of
the two strands of a DNA helix is used as the
template
• RNA contains uracil rather than thymine
Messenger RNA=mRNA
Transfer RNA=tRNA
Ribosomal RNA=rRNA
9-57
Figure 9.22
9-58
Messenger RNAs
• Contain protein coding information
ATG start codon to UAA, UAG, UGA Stop Codon
A cistron is the unit of RNA that encodes one
polypeptide chain
• Base pairing/3D structure is the exception
Can be used to regulate RNA stability termination,
RNA editng, RNA splicing
Transfer RNA (tRNA)
• Is a single strand folded into a cloverleaf
shape
• Has a specific site to which specific amino
acids can attach
• There is a different type of tRNA for each
type of amino acid
• Each type of tRNA has three bases which
are specific to the type of amino acid which
will attach
• These three bases are called the anticodon
tRNA
Specific amino acid attaches
More simply
drawn
Anticodon – specific to the amino acid which
attaches to this tRNA molecule
‫متابولیسم اسیدهای نوکلئیک‬
Degradation of nucleic acid
Nucleoprotein
In stomach
Gastric acid and pepsin
Nucleic acid
Protein
In small intestine
Endonucleases: RNase and
DNase
Nucleotide
Nucleotidase
Phosphate
Nucleoside
Nucleosidase
Base
Ribose
Significances of nucleotides
1. Precursors for DNA and RNA synthesis
2. Essential carriers of chemical energy, especially
ATP
3. Components of the cofactors NAD+, FAD, and
coenzyme A
4. Formation of activated intermediates such as
UDP-glucose and CDP-diacylglycerol.
5. cAMP and cGMP, are also cellular second
messengers.
There are two pathways leading to
nucleotides
• De novo synthesis: The synthesis of nucleotides
begins with their metabolic precursors: amino
acids, ribose-5-phosphate, CO2, and one-carbon
units.
• Salvage pathways: The synthesis of nucleotide
by recycle the free bases or nucleosides released
from nucleic acid breakdown.
§ 2.1 De novo synthesis
• Site:
in cytosol of liver, small intestine and thymus
• Characteristics:
a. Purines are synthesized using 5phosphoribose(R-5-P) as the starting material
step by step.
b. PRPP(5-phosphoribosyl-1-pyrophosphate) is
active donor of R-5-P.
c. AMP and GMP are synthesized further at the
base of IMP(Inosine-5'-Monophosphate).
Purine Nucleotide Synthesis
Purine Nucleotide Synthesis
2-
O3P O CH2
H
O
H

H
H
OH
OH
OH
-D-Ribose-5-Phosphate (R5P)
ATP
Ribose
Phosphate
Pyrophosphokinase
AMP
2-
O3P O CH2
O
H
H
H
H

O
O
P
O
O
P
O
OH
OH
O
O
5-Phosphoribosyl--pyrophosphate (PRPP)
Glutamine
+ H2O
Amidophosphoribosyl
O
C
Transferase
HN
Glutamate
+ PPi
2-
O3P O CH2
H
b
H
H
H
OH
HC
NH2
O
OH
b-5-Phosphoribosylamine (PRA)
C
C
N
4
CH
5
N
N
2-
O3P O CH2
H
H
OH
O
H
H
OH
Inosine Monophosphate (IMP)
P
P
O CH2 O
Bas e
ribonucleotide
reductase
Mg 2+
OH
OH
P
P
O CH2 O
H 2O
thioredoxin S
S
SH
thioredoxin
NDP
SH
£¨ N=A, G, C, U£©
FAD
+
NADP
thioredoxin
reductase
NADPH + H
OH
Bas e
H
dNDP
ATP
+
kinase
ADP
dNTP
Deoxyribonucleotide synthesis at the NDP level
Purine nucleotide biosynthesis is regulated by feedback
inhibition
Purine Salvage Pathway
.
adenine
phosphoribosyl transferase
Adenine
PRPP
AMP
PPi
O
N
O
N
2-O
N
N
N
Hypoxanthine
O
N
N
hypoxanthine-guanine
phosphoribosyl transferase
(HGPRT)
PRPP
N
N
Guanine
NH2
3POH2C
O
N
N
N
HO OH
IMP
O
PPi
N
2-O
3POH2C
O
N
N
N
NH2
HO OH
GMP
.
Absence of activity of HGPRT leads to Lesch-Nyhan syndrome.
‫تجزیه و دفع بازهای پورین‬
‫‪-‬‬
Gout
Impaired excretion or overproduction of uric acid
Uric acid crystals precipitate into joints (Gouty
Arthritis), kidneys, ureters (stones)
Lead impairs uric acid excretion – lead poisoning
from pewter drinking goblets
Fall of Roman Empire?
Xanthine oxidase inhibitors inhibit production of
uric acid, and treat gout
Allopurinol treatment – hypoxanthine analog that
binds to Xanthine Oxidase to decrease uric acid
production
The uric acid and the
gout
Out of body
In urine
Diabetese
nephrosis
……
Hypoxanthine
Xanthine
Uric acid 
Over 8mg/dl, in the plasma
Gout, Urate crystallization
in joints, soft tissue, cartilage and kidney
ALLOPURINOL IS A XANTHINE OXIDASE INHIBITOR
A SUBSTRATE ANALOG IS CONVERTED TO AN INHIBITOR, IN
THIS CASE A “SUICIDE-INHIBITOR”
Element source of pyrimidine
base
C
Gl n
N3
4
C
5
As p
C O2
C
2
1
N
6C
synthesis of carbamoyl phosphate
•Carbamoyl phosphate synthetase(CPS) exists in 2 types:
•CPS-I, a mitochondrial enzyme, is dedicated to the urea cycle and
arginine biosynthesis.
•CPS-II, a cytosolic enzyme, used here. It is the committed step in
animals.
2 ATP +
2 ADP +
Glutamate +
Pi
HCO3 + Glutamine
+ H2O
Carbamoyl
Phosphate
Synthetase II
Pyrimidine Synthesis
NH2
O
TMP
C
PO3-2
O
CMP
Carbamoyl Phosphate
Aspartate
Aspartate
HO
Transcarbamoylase
(ATCase)
2
Pi
O
Dihydroorotase
C
O
C
C
O
PRPP
PPi
2-
O3P
O
CH2
H
C
N
H
Orotate
CH
C
CH
N
O
CH
HN
HN
O
H
COO
Orotate Phosphoribosyl
Transferase
b
H
H
OH
OH
Uridine Monophosphate
(UMP)
Synthesis of UMP from carbamoyl phosphate
5. Regulation of de novo synthesis
ATP + CO2 + Gln
carbamoyl phosphate
purine
nucleotide
carbamoyl aspartate
PRPP
ATP + R-5-P
UM P
pyrimidine nucleotide
UTP
CTP
‫تجزیه ودفع بازهای پیریمیدین‬
Thymidine
Cytosine
Uracil
γ aminoisobutyrate
γ aminoisobutyrate
CO2+NH3
β alanine +CO2+NH3
Succinyl COA
Pyrimidine Catabolism
enzyme specification.