Basic structure of hair and hair growth cycle.pptx
Carbohydrates Lecture.pptx
1. Carbohydrates
Dr. Omeed Akbar Ali
P h D . C l i n i c a l B i o c h e m i s t r y
T i k r i t U n i v e r s i t y - C o l l e g e o f M e d i c i n e
1
2. Carbohydrates
2
Carbohydrate is a biomolecule consisting of carbon (C), hydrogen (H) and
oxygen (O) atoms with general formula of Cm(H2O)n
CH2O
(CH2O)x C6H12O6
Carbohydrates Biosynthesis
Carbohydrates are predominantly biosynthesized by plants through photosynthesis.
Glucose is synthesized in plants from CO2, H2O, and solar energy from the sun.
chlorophyll
CO2 + H2O CH2O + O2
Sunlight aldehyde
5. Sugar structure
Most names for sugars end in -ose
Classified by number of carbons
6C = hexose (glucose)
5C = pentose (ribose)
3C = triose (glyceraldehyde)
6. 6
Types of Carbohydrates
Classification based on the number of sugar units in
the total chain
Monosaccharides
Disaccharides
Oligosaccharides
Polysaccharides
9. Types of Carbohydrates
Oligosaccharides
up to 3-12 sugar units:
- Maltotriose
9
Polysaccharides
• Large polymers
> 13 sugar units:
Homo-polysaccharides are polysaccharides composed of a single type of sugar monomer. For
example, Starch, Cellulose and Glycogen.
Hetero-polysaccharides are polysaccharides that contain multiple monosaccharide units. Many
naturally occurring heteropolysaccharides have peptides, proteins, and lipids attached to them.
Some heteropolysaccharides examples are: Peptidoglycans, Agarose and Glycosaminoglycans.
10. Polysaccharides
10
Polymers of sugars
costs little energy to build
easily reversible = release energy
Function:
energy storage
starch (plants)
glycogen (animals)
in liver & muscles
11. Functions of Carbohydrates
Source of energy for living beings, e.g. glucose.
Storage form of energy, e.g. glycogen in animal tissue and starch in plants.
Serve as structural component, e.g. glycosaminoglycans in humans, cellulose in
plants and chitin in insects.
Non-digestable carbohydrates like cellulose, serve as dietary fibers.
Constituent of nucleic acids RNA and DNA, e.g. ribose and deoxyribose sugar.
Play a role in lubrication, cellular intercommunication and immunity.
Carbohydrates are also involved in detoxification, e.g. glucuronic acid.
11
12. 12
Thus Carbohydrates are chief
constituents of human food.
R.D.A for Dietary Carbohydrates=
400-600 gm/day.
13. Digestion, Absorption And Transport Of Carbohydrates
• The principal sites of carbohydrate digestion are the mouth and small intestine.
• Digestion in Mouth: Salivary glands secrete α-amylase (ptylin), which initiates the
hydrolysis of a starch. breaking some α-(1 → 4) bonds, α- amylase hydrolyzes starch
into dextrins.
• Digestion in Intestine: There are two phases of intestinal digestion.
1. Digestion due to pancreatic α-amylase
2. Digestion due to intestinal enzymes : sucrase, maltase, lactase, isomaltase.
13
15. Absorption And Transport Of Carbohydrates
Carbohydrates are absorbed as monosaccharides from the intestinal lumen.
• Two mechanisms are responsible for the absorption of monosaccharides:
1. Active transport against a concentration gradient, i.e. from a low glucose
concentration to a higher concentration.
2. Facilitative transport, with concentration gradient, i.e. from a higher
concentration to a lower one.
15
17. Introduction to Metabolism
17
Metabolism: The sum of the chemical changes that convert nutrients into energy and
the chemically complex products of cells Hundreds of enzyme reactions organized
into discrete pathways.
• Substrates are transformed to products via many specific
intermediates Metabolic maps portray the reactions.
• Metabolism consists of catabolism and anabolism
18. Introduction to Metabolism
Catabolism: degradative pathways
Usually energy-yielding!
“destructive metabolism”
FUELS -> -> CO 2 + H 2 O + useful energy.
Anabolism: biosynthetic pathways
Energy-requiring!
“Constructive metabolism”
Useful energy + small molecules --> complex molecules.
18
19. Metabolism of Carbohydrates
19
Carbohydrate metabolism is a fundamental biochemical process that ensures a
constant supply of energy to living cells.
The most important carbohydrate is glucose, which can be broken down via
glycolysis, enter into the Kreb's cycle and oxidative phosphorylation to generate
ATP.
22. Glycolysis
22
Glycolysis: A process in which glucose is partially broken
down to two molecules of pyruvate (it is converted into lactate
finally ) by cells in enzyme reactions that do not need oxygen.
Glycolysis is also called anaerobic oxidation.
Position of glycolysis:cytoplasm
23. 23
Phase I------ glycolytic pathway: The six-carbon glucose break down
into two molecules of the three-carbon pyruvate.
Phase II: Pyruvate is converted to lactate or Acetyl-CoA.
1. Glycolysis Has Two Phases:
Glycolysis
(Cytoplasm)
Acetyl-CoA
(Mitochondria)
31. 6. Oxidation of Glyceraldehyde 3-
Phosphate to 1,3-Bisphosphoglycerate
32. 7. Phosphoryl Transfer from 1,3
Bisphosphoglycerate to ADP
The formation of ATP by
phosphoryl group transfer
from a substrate such as
1,3-bisphosphoglycerate is
referred to as a substrate-
level phosphorylation
35. ADP ATP
K+ Mg2+
pyruvate kinase
10. Transfer of the Phosphoryl Group
from Phosphoenolpyruvate to ADP
Phosphoenolpyruvate
COOH
C
CH2
P
P
O
Pyruvate
COOH
C=O
CH3
37. Position of glycolysis:cytoplasm
Glycolysis is an anaerobic process through which ATP is synthesized .
There are three irreversible steps in the process.
G G-6-P
ATP ADP
Hexokinase
ATP ADP
F-6-P F-1,6-2P
PFK-1
ADP ATP
PEP Pyruvate
Pyruvate kinase
Summary of glycolysis
Key
Enzymes
① Hexokinase
② Phosphofructokinase-1
③ Phosphoglycerate kinase
2. Regulation of Glycolysis: 3 key
enzymes
ADP ATP
F-1,6-P 3- P Glycerate
PGK
④ Pyruvate kinase
38. 38
38
Phase II: Pyruvate is converted to lactate or Acetyl-CoA .
Pyruva
te
COOH
C=O
CH3
Lacta
te
COOH
CHOH
CH3
NADH + H+
NAD+
Acetyl-CoA
NADH+H+
CO2
TAC
Citrate
Co2 + NADH + H+
CoA-SH + NAD+
39. 39
OVERVIEW
Acetyl coA, the precursor for fatty acid
synthesis is produced from pyruvate,
ketogenic amino acids, fatty acid
oxidation and by alcohol metabolism.
It is a substrate for TCA cycle and a
precursor for Oxidation , ketone bodies
and faty acids.
41. Definition of Tri-carboxylic Acid Cycle
The citric acid cycle is a series of reactions that brings about catabolism
of acetyl-coA liberating reducing equivalents which upon oxidation through
respiratory chain of mitochondria, generate ATP.
It plays a central role in the breakdown or catabolism of organic fuel molecules—i.e
glucose and some other sugars, fatty acids, and some amino acids. Before these rather
large molecules can enter the TCA cycle they must be degraded into a two-carbon
compound called acetyl coenzyme A (acetyl CoA). Once fed into the TCA cycle, acetyl
CoA is converted into carbon dioxide and energy.
41
42. CoASH
NADH+H+
NAD+
CO2
NAD+
NADH+H+
CO2
GTP
GDP+Pi
FAD
FADH2
NADH+H+
NAD+
H2O
H2O
H2O
CoA-SH
CoA-SH
⑧
①
②
③
④
⑤
⑥
⑦
②
H2O
① Citrate Synthase
② Aconitase
③ Isocitrate Dehydrogenase
④ α-ketoglutarate dehydrogenase complex
⑤ Succinyl-CoA Synthetase
⑥ Succinate Dehydrogenase
⑦ Fumarase
⑧ Malate Dehydrogenase
GTP GDP
ATP
ADP
Nucleoside Diphosphate Kinase
1. The condensation of acetyl-CoA
with oxaloacetate to form
citrate.
2. Formation of Isocitrate via cis-
Aconitate.
3. Oxidation of Isocitrate to α-
Ketoglutarate and CO2.
4. Oxidation of α-Ketoglutarate to
Succinyl-CoA and
CO2.
5. Conversion of Succinyl-CoA to
Succinate.
6. Oxidation of Succinate to Fumarate.
7. Hydration of Fumarate to Malate.
8. Oxidation of Malate to
Oxaloacetate
1. The Citric Acid Cycle Has Eight Steps
43. Energetics : 2 Acetyl CoA from 2 Pyruvate
1NADH+H+ = 3/2.5 ATP
1FADH2 = 2/1.5 ATP
1GTP = 1 ATP
Acetyl-CoA + 3 NAD+ + [FAD] + GDP + Pi + 2 H2O CoA-SH
+ 3 NADH+3 H + +[FADH2] + GTP + 2 CO2
12 ×2=24
44. Indicator molecules of higher energy
state i.e. ATP, NADH, citrate, Acetyl
CoA – inhibit TCA cycle
Indicator molecules of low energy
state i.e. ADP, AMP, NAD+ – stimulate
TCA cycle
*
*
*
*
45. Citrate synthase- There is allosteric inhibition of citrate synthase by ATP and long-chain
fatty acyl-CoA.
Isocitrate dehydrogenase- is allosterically stimulated by ADP, which enhances the
enzyme's affinity for substrates. In contrast, NADH inhibits iso-citrate dehydrogenase by
directly displacing NAD+. ATP, too, is inhibitory.
α-ketoglutarate dehydrogenase -α- Ketoglutarate dehydrogenase is inhibited by
succinyl CoA and NADH. In addition, α-ketoglutarate dehydrogenase is inhibited by a
high energy charge. Thus, the rate of the cycle is reduced when the cell has a high level
of ATP.
Succinate dehydrogenase is inhibited by oxaloacetate, and the availability of
oxaloacetate, as controlled by malate dehydrogenase, depends on the [NADH]/[NAD+]
ratio.
48. 48
Distribution of glycogen
Hepatic glycogen:
The glycogen content of the liver
is up to 8% of the fresh weight.
Muscle glycogen:
The glycogen concentration
in muscle is 1-2%.
49. 49
Position:
Cytoplasma of liver, muscle …
1. Most anabolism of glycogen occurred
in liver and muscle.
Definition:
The synthesis progress of glycogen from monosaccharide is named glycogenesis.
Monosaccharide:
Glucose (main), fructose, galactose …
50. 50
Glucose is converted to glucose 6-phosphate
ATP ADP
Glucokinase
Mg2
+
glucose
O H
H
H
H
O
H
OH
H OH
OH
CH2OH
glucose-6-
phosphate
O H
H
H
H
O
H
OH
H OH
OH
CH2OPO3H2
Glucose + ATP glucose-6-phosphate + ADP
Glucose-6-phosphate is isomerized to glucose-1-phosphate
O
H
OH
O
P
O
H
O
CH2
OH
OH
OH
O
Glucose-1-phosphate
Phosphogluco Mutase
P
O
OH
OH
O
O
CH2
OH
OH
OH
OH
Glucose-6-phosphate
51. 51
The generation of UDP-glucose
O H
H
H
H
O
H
OH
H OH
O
CH2OH
P
O
OH
OH
glucose-1-
phosphate
UDPG
pyrophosphorylase
O H
H
H
H
O
H
OH
H OH
O
CH2OH
P
O
OH
O ÄòÜÕ
P
O
O
H
O
UDPG
(uridine diposphate glucose)
PPi
Urdine
UTP
52. 52
The glucose in UDPG is attached to glycogen primer
ÄòÜÕ
P
P
O H
H
H
H
O
H
OH
H OH
CH2OH
UDPG
R
O
H O
O H
H
H
H
OH
H OH
CH2OH
O
O
H
H
H
H
OH
H OH
CH2OH
Gn
(Glycogen Primer)
R
O O
O H
H
H
H
OH
H OH
CH2OH
O
O
H
H
H
H
OH
H OH
CH2OH
O H
H
H
H
O
H
OH
H OH
CH2OH
Glycogen synthase
Gn+
(glycog
UDP
Urdine
α-(1,4)
53. 53
Energy consumption
need primer
nonreducing end
glucose
G-1-P
Glycogen (1→4 and 1→6
glucose unit)
G-6-P
ATP
ADP
UDPG
UTP
PPi
Glycogen (1→4 glucose unit)
Glycogen primer
UDP
Branching enzyme
54. 54
2. The production of glycogen degradation: glucose could replenish the blood
glucose
Position:
Liver
Production:
Glucose
Glycogen-degrading
The progress that glycogen is degraded to glucose.
Glycogenolysis
55. Glycogen is phosphorolytic cleavaged to G-1-P
PHOSPHORYLASE Rate-limiting enzyme
Gn
Gn-1
H3PO4
O
H
OH
O
P
O
H
O
CH2
OH
OH
OH
O
glucose-1-phosphate
Gn+ H3PO4 G-1-P + Gn-1
Phosphorylase
R
O
H O
O H
H
H
H
OH
H OH
CH2OH
O
O
H
H
H
H
OH
H OH
CH2OH
Gn
(glycogen primer)
R
O O
O H
H
H
H
OH
H OH
CH2OH
O
O
H
H
H
H
OH
H OH
CH2OH
O H
H
H
H
O
H
OH
H OH
CH2OH
56. 56
The function of
debranching enzyme
G
G-1-P
Pi
Debranching enzyme
has two activities:
α-1,4- transglycosylase
α-1,6- glycosidase
Debranching enzyme
Debranching enzyme
57. 57
G-1-P is converted to G-6-P
O
H
OH
O
P
O
H
O
CH2
OH
OH
OH
O
glucose-1-phosphate
P
O
OH
OH
O
O
CH2
OH
OH
OH
OH
glycophosphomutase
glucose-6-phosphate
G-6-P is hydrolyzed to Glucose
glucose
O H
H
H
H
O
H
OH
H OH
OH
CH2OH
glucose-6-phosphate
O H
H
H
H
O
H
OH
H OH
OH
CH2OPO3H2
H3PO4
H2O
Glucose -6 - phosphatase
(liver)
This enzyme is deficient in brain and muscle
58. 58
Scheme of the glycogen-
degradation
Glycogen
Gn+1
G-1-P
Pi
Gn
phosphorylase
G-6-P
glucophosphomutase
Glucose
H2O
Pi
Glucose-6-phosphatase
Catabiosis of
carbohydrate
59. 59
The synthesis and degradation of glycogen
UDPG pyrophosphorylase
G-1-P
UTP
UDPG
PPi
Gn+1
UDP
G-6-P Glucose
Glycogen synthase
glucophosphomutase
Hexokinase (glucokinase)
Gn
Pi
phosphorylase
Glucose-6-phosphatase(liver)
Gn
60. 60
liver glycogen Muscle glycogen
Storage 90-100g 200-500g
≤5% 1-2%
Raw material Monosaccharide/no-
carbohydrate material
Glucose
cleavage Glucose lactate
function To maintain relatively
stable of blood glucose
To meet the energy
requirement of muscles
strenuous exercise
consumption 12-18h after meal After heavy exercise
Comparison of liver glycogen and muscle glycogen
62. 62
Gluconeogenesis is the synthesis progress of glucose or glucogen from
non-carbohydrate sources.
Position:
Substrance:
Definition:
Cytoplasma and mitochondria of liver , kidney cells.
Pyruvate, lactate, glycerine, glycogenic amino acid.
Gluconeogenesis
Wher
e
64. 64
Progress:
Three irreversible reactions catalyzed by three key enzymes in
glycolysis must by bypassed in gluconeogenesis.
Most reactions of gluconeogenic pathway and glycolytic pathway
are shared and reversible.
gluconeogenic pathway is the synthesis progress of glucose
from pyruvate.
①
②
65. 65
1. Pyruvate is converted to PEP by pyruvate carboxylation bypass
Pyruvate oxalacetate PEP
ATP ADP+Pi
CO2
①
GTP GDP
CO2
②
① pyruvate carboxylase, coenzyme is biotin (in mitochondria).
② PEP-carboxykinase ( mitochondrion, cytoplasma)
67. 67
Pyruvate Pyruvate
oxaloacetate
pyruvic carboxylase
ATP + CO2
ADP + Pi
Malate
NADH + H+
NAD+
Aspartate
glutamate
α-ketoglutarate
Aspartate
Malate oxaloacetate
PEP
PEP-carboxykinase
GTP
GDP + CO2
mitocondria
cytoplasma
Lactate
Alanine
NADH + H+
NAD+
NADH + H+ NAD+
ALT LDH
68. 68
The resource of NADH+H+ in glyconeogenesis:
The generation of glyceraldehyde-3-phosphate from 1,3-bisphosphoglycerate
need NADH+H+ in glyconeogenesis.
NADH+H+ is provide from latate when the latate is the resource of glyconeogenesis.
If amino amid is the resource of glyconeogenesis, NADH+H+ come from mitochondria
where NADH+H+ are derived from β- oxadation of fatty acid or TAC. The transport of
NADH+H+ dependent on the conversion of oxaloacetate and malate.
69. 69
2. Conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate
3. Conversion of Glucose 6-Phosphate to Glucose
71. 71
1. The Main Function Of Gluconeogenesis: Maintain The Stable Of Blood Glucose
The maintenance of stable blood glucose is dependent on the gluconeogenesis from amino
acid, glycerine when fasting or starvation.
Under normal conditions, brain utilized energy derived from glucose because brain cells could
not take energy from fatty acid; erythrocytes get the energy through glycolysis totally in
the absence of mitochondria; and, bone marrow, nerves tissure are used to take
glycolysis because of their active metabolism. Above mentioned glucose are generated
through the gluconeogenesis.
2. The Physiological Significance Of Gluconeogenesis Is To Maintain
The Stable Of Blood Glucose.
72. 72
The substrate of gluconeogenesis are lactate, amino acid and glycerine.
Lactate come from the muscle glycogenolysis related with exercise intensity.
Amino acid and glycerine are the substrate of gluconeogenesis when in hungry.
73. 73
2. Gluconeogenesis is an important pathway to replenish and restore the
storage of liver glycogen
C3 pathway: After meal, most glucose is broken down to lactate or pyruvate which
contain three carbons outside the liver cells, then these C3 substrates enter the liver cells
and generate to glucogen by gluconeogenesis.
In muscle lactate can by produced by glycolysis. Gluconeogenic capacity of muscle is very low, so
lactate diffused into blood and transported to the liver. In the liver, glucose is synthesized from
lactate by gluconeogenesis. After glucose is released into blood, it can be taken up by muscle,
which formed a cycle named Lactate cycle or Cori cycle.
Because the enzymes in the liver and muscle are different, they could contribute to the formation
of lactate cycle.
3. Lactate cycle:
75. 75
Significance:
Avoid waste of lactate
Protect from acidosis caused by accumulation of lactate
Lactate cycle consumes energy:
6 ATP are needed when 2 lactate are generated to 1 glucose.
78. Definition
Pentose phosphate pathway is the progress
of glucose produces pentose phosphates and
NADPH+H+, then the pentose phosphates is
converted into Glyceraldehyde 3-phosphate and
fructose 6-phosphate.
Pentose phosphate pathway produces pentose phosphates and
NADPH + H+
79. Position:Cytosol
Phase I: The Oxidative Phase
1. The Progress Of Pentose Phosphate Pathway has Two
Phases:
The reaction has two phases:
Phase II:The Nonoxidative Phase
Produces Pentose Phosphates, NADPH+H+ and CO2
Including a series of group transfer.
81. The glucose 6-phosphate dehydrogenase which catalyze the first step is the
key enzyme of the pathway.
H+ produced in two dehydrogenations were accepted by NADP+ to generate
NADPH + H+ .
ribose phosphate generated in reaction is a very important intermediated
product.
G-6-P
Ribose
5-phosphate
NADP+ NADPH+H+ NADP+ NADPH+H+
CO2
82. The significance of phase II is the transformation of ribose to fructose 6-
phospherate and Glyceraldehyde 3-phosphate by a series of group transfer
reaction, then enter the glycolysis. So, pentose phosphate pathway is also named
pentose phosphate shunt.
2.Enter the glycolysis by the group transfer reaction
86. Hydrogen receptor of dehydrogenation is NADP+ , to generate NADPH+H+。
Transaldolase and transketolase catalyze the interconversion of three-, four-,
five-, six-, and seven-carbon sugars, with the reversible conversion of six
pentose phosphates to five hexose phosphates.
The reaction provides specialized intermediated product: ribose 5-phosphate.
One CO2 and two NADPH+H+ were generated by one G-6-P through one
decarboxylation and two dehydrogenation in a cycle.
Characteristic of pentose phosphate pathway:
87. 2. The pentose phospherate pathway is regulated mainly by
the ratio of NADPH/NADP+
Glucose-6-phosphate dehydrogenase is the key enzyme of the pentose phosphate
pathway, the activity of this enzyme decide the flow of glucose-6-phosphate which
enter the pathway.
The G-6-P-D is inhibited by a high ratio of NADPH/NADP+ and increased
consumption of NADPH .
Therefore, the flow of pentose phospherate pathway meets the needs of the cells
for NADPH.
88. 3. the significance of pentose phospherate is the generation of
NADPH and ribose 5-phosphate
2.Provide NADPH as hydrogen donor to participate in various metabolic
reactions
1.Provide ribose for biosynthesis of nucleotides.
(1)NADPH is the hydrogen donor in various anabolic;
(2)NADPH participate the hydroxylation in vivo.
(3)NADPH could keep the regeneration of reduced
glutathione (GSH).
89. Favism:
some people are Glucose 6-Phosphate Dehydrogenase (G6PD) deficient. their
erythrocytes will lyse after ingestion of the beans (containing divicine or other oxidizing
agents), releasing free hemoglobin into the blood (acute hemolytic anemia).
G6PD deficiency is a X-linked recessive genetic disease. X-linked diseases usually occur in
males. Males have only one X chromosome. A single recessive gene on that X
chromosome will cause the disease. The geographic distribution of G6PD deficiency is
instructive. It is common in the South than in the northern population