bio l4,5
TRANSCRIPT
How is carbohydrate digested and absorbed
in our body.
Metabolism of Glycogen in the body
Glycogen metabolism diseases.
Difference between glycogen in the liver and
in the muscle.
Dr. Hani Alrefai 04/11/2014
1- Passive diffusion (Simple absorption): The absorption depends upon the concentration gradient of sugar between intestinal lumen and intestinal mucosa. This is true for pentoses and fructose.
2- Facilitative diffusion: by Na+-independent glucose transporter system (GLUT 5). There are a mobile carrier protein responsible for transport fructose, glucose, and galactose with their conc. gradient.
Dr. Hani Alrefai 04/11/2014
3- Active transport: by sodium-dependent glucose transporter system (SGLUT 1). In the intestinal cell membrane there is a mobile carrier protein coupled with Na+-K+ pump. The carrier protein has 2 separate sites one for Na+ & the other for glucose. It transports Na
+ ions (with cone. gradient) and glucose (against its cone. gradient) to the cytoplasm of the cell . Na+ ions is expelled outside the cell by Na+-K+ pump which needs ATP and expel 3 Na+ against 2 K+.
Dr. Hani Alrefai 04/11/2014
Glucose is transported through cell membrane of different tissues by different protein carriers or transporters as follows :
1- GLUT 1 : present mainly in red blood cells.
2- GLUT 2 : present in liver, kidneys, pancreatic B cells and lateral border of small intestine, for rapid uptake and release of glucose.
3- GLUT 3 : present mainly in brain.
4- GLUT 4 : present in muscles (Skeletal and cardiac) and adipose tissues. (Insulin)
5- GLUT 5 : present in small intestine for sugar absorption.
6- SGLUT 1 : present in small intestine and kidneys.
Dr. Hani Alrefai 04/11/2014
Def.: it is the formation of glycogen from
glucose in muscles and from CHO and non
CHO substances in liver.
Site and location: In the cytoplasm of every
cell mainly liver and muscles.
Steps:
Dr. Hani Alrefai 04/11/2014
Steps:
3. Glycogen synthase enzyme in presence of pre-existing glycogen primer (glycogenin) will add glucose mol. from UDP-G by forming l :4 glucosidic link.
4. When the chain has been lengthened, the branching enzyme (glucan transeferas) transfers a part of the a 1:4 chain to a neighbouring chain to form an l:6 glucosidic link. Thus establishing the branching points in the molecule. The branches grow by further addition of 1:4 glucosyl units.
Dr. Hani Alrefai 04/11/2014
Def.: It is the breakdown of glycogen into glucose in liver and lactic
acid in muscles.
Steps: 1. Phosphorylase enzymes attacks only a 1:4 glucosidic link at
the end of the chain until there are 4 molecules of glucose near the branching point giving G-l-P in presence of Pi.
2. Transferase enzyme transfers trisaccharides unite (from this 4 mol.) from one branch to another exposing a l: 6 branching point.
3. The branching point is splitted by debranching enzyme giving free glucose.
4. G-l-P is changed to G-6-P by the action of phosphoglucose mutase enzyme.
5. G-6-P is hydrolysed into free glucose and Pi by the action of G-6-phosphatase -> free glucose diffuse from liver cell to blood stream. In muscles there is no G-6-phosphatase -> so G-6-P by glycolysis will give lactic acid.
Dr. Hani Alrefai 04/11/2014
The key regulatory enzyme of glycogenesis is
glycogen synthase which present in 2 forms: - Active form which is dephosphorylated enzyme.
- Inactive form which is phosphorylated enzyme.
The key regulatory enzyme of glycogenolysis is
phosphorylase enzymes which present 2
forms. -Active form which is phospho -phosphorylase enzymes.
-Inactive form which is Dephospho-phosphorylase .
Dr. Hani Alrefai 04/11/2014
Epinephrine stimulates α adrenergic receptor → activate PLC → hydrolyse PIP2→ IP3 → Ca+
from endoplasmic reticulum → Ca+ reacts with calmoduline to give Ca+-calmoduline complex → stimulate PKC (protein kinase C) phosphorylation of :
→glycogen synthase (inactive form) → phosphorylase(active form)
→ → → → → stimulate glycogenolysis and inhibit glycogenesis.
Dr. Hani Alrefai 04/11/2014
Epinephrine stimulates β adrenergic
receptors and Glucagon stimulates its receptors → stimulate adenylate cyclase enzyme →
cyclic AMP formation → stimulate protein kinas A phosphorylation of:
→glycogen synthase (inactive form) → phosphorylase(active form)
→ → → → → stimulate glycogenolysis and inhibit glycogenesis.
Dr. Hani Alrefai 04/11/2014
Insulin
Stimulate phosphatase enzyme dephosphorylation of :
→glycogen synthase (active form)
→ phosphorylase(inactive form)
→ → → → → inhibit glycogenolysis and
stimulate glycogenesis.
Also stimulate phosphodiesterase enzyme → destruct
cyclic AMP.
Dr. Hani Alrefai 04/11/2014
Liver glycogen Muscle glycogen
- Amount Liver has more conc. muscle has more amounts.
- Sources blood glucose and other
radicals
blood glucose only
- Hydrolysis give blood glucose due to absence of
phosphatase enzyme not
give free glucose but give
lactic acid
- Starvation changes to blood glucose not affected.
- Muscular ex. depleted. depleted.
- Hormones insulin → ↑↑↑
adrenaline →↓↓↓
thyroxine →↓↓↓
glucagons →↓↓↓
insulin → ↑↑↑
adrenaline → ↓↓↓
Thyroxine → ↓↓↓
glucagons → no
effect due to absence of its
receptors
Dr. Hani Alrefai 04/11/2014
A group of diseases results from genetic defects of certain enzymes.
1. Von Gierke (type I) hepatorenal glycogen storage disease: glucose-6-phosphatase enzyme
2. Pompe's (lysosomal glucosidase deficiency).
3. Forbe's (Debranching enzyme efficiency).
4. Andersen's (Branching enzyme system deficiency).
5. McArdle's (Muscle phosphorylase deficiency).
6. Hers's (Liver phosphorylase deficiency).
7. Taui's (Phosphofuctokinase deficiency).
Dr. Hani Alrefai 04/11/2014
Regulation of Glycolysis
Carbon sources of gluconeogenesis
Cori cycle
Krebs cycle
Energy production of glucose oxidation
Dr. Hani Alrefai 04/11/2014
Def.:
glycolysis is oxidation of glucose to give pyruvic
acid in presence of O2 and lactic acid in absence
of O2 and in RBCs.
Site:
Cytoplasm of all cells.
Dr. Hani Alrefai 04/11/2014
G → G-6-P -1
F-6-P → F l:6diphosphate -1
(1,3 DPG → 3-phosphoglycerate)X2 +2
(Phosphoenol pyruvate → pyruvate)X2 +2
Net ATP/mol glucose (anerobic) 2
2NADH+H from Glyceraldhyde3PD +4 or 6
Net ATP/mol glucose (aerobic) 6 or 8
If we started in the muscle from glycogen we start
from G-6-P so we have 1 extra ATP
Dr. Hani Alrefai 04/11/2014
Enzymatic:
Hexokinase
Glucokinase
PFK
PK
Hormonal:
Glucagon
cAMP
Represion of Key
reg. enzymes
Insulin
Phosphatase
cAMP
Induction of Key
reg. enzymes
Dr. Hani Alrefai 04/11/2014
Regulations:
1. Iodoacetate:
inhibits glyceraldehyde-3-P dehydrogenase
2. Fluoride:
inhibits enolase
Dr. Hani Alrefai 04/11/2014
Aerobic
glycolysis
Anaerobic
glycolysis
Site Cytoplasm of all
tissues
RBCs and
skeletal muscle
during muscular
ex.
End products Pyruvic acid +
NADH.H+
Lactic acid +
NAD+
Energy
production
6 OR, 8 ATP 2 ATP
Lactate
dehdyrogenase
Not needed Needed
Dr. Hani Alrefai 04/11/2014
Def.:
It is the formation of glucose form non CHO sources.
Function :
Its main function is to supply blood glucose in cases of
carbohydrate deficiency (fasting, starvation and low
carbohydrate diet).
Sites:
Cytoplasm and mitochondria of liver and kidney
tissues (due to presence of glucose-6-phosphatase and
fructose-1,6-biphosphatase)
Dr. Hani Alrefai 04/11/2014
1- Propionic acid:
It is the product of odd number fatty acid
oxidation by β oxidation
2- Glycerol
3-Glucogenic amino acids:
Amino acids by deamination can be converted
into α-keto acids as pyruvic, α ketoglutaric and
OAA → they can be converted into glucose.
Proteins are considered as one of the main
sources of blood glucose especially after 18
hours due to deplation of liver glycogen.
Dr. Hani Alrefai 04/11/2014
4-Lactic acid (Cori cycle):
In vigorous skeletal muscle activity, large amount
of lactic acid produced → passes to the liver
through blood stream → converted in liver into
pyruvic acid and lastly to glucose→ reach muscle
once again through blood → this cycle called
Cori cycle.
Importance of Cori cycle:
1- It prevents loss of lactate as waste products in urine.
2- Oxidation of reduced NAD.
3- It supplies red cells and contracting muscles with
glucose for reutilization and ATP production.
Dr. Hani Alrefai 04/11/2014
5- Glucose – alanine Cycle:
During starvation there is muscle protein catabolism → NH3 and pyruvic acid (produced from glycosis), → alanine is formed → reach liver and converted into pyruvic acid which give glucose through gluconeogenesis and NH3 which converted into urea → excreted in urine.
Significant of glucose alanine cycle:
1. Disposal of NH3 produced from muscle protein catabolism through formation of urea which excreted in urine.
2. Prevent accumulation of lactic acid which change PH of blood.
3. Conserve NAD/NADH-H+ ratio.
4- It supplies muscles with glucose for ATP production.
Dr. Hani Alrefai 04/11/2014
Def.:
It is conversion of pyruvic acid and other α-keto acids
into CoA derivatives.
Site:
In mitochondrial matrix of all tissues except RBCs.
Enzyme:
pyruvate dehydrogenase complex which composed of
3 enzymes act cooperative with each other
5 co-enzymes: TPP - lipoic – acid – CoASH – FAD –
NAD
Energy production:
NAD ---- NADH+H = 3ATP (1 mol gluc = 6 ATP)
Dr. Hani Alrefai 04/11/2014
Def.:
It is the series of reactions in mitochondria which
oxidize acetyl CoA to CO2 , H20 and energy.
During oxidation in the cycle, hydrogens are
transferred to NAD+ and FAD then to the
respiratory chains for ATP synthesis.
Site:
Mitochondria of all tissue cells except RBCs.
The enzymes of the cycle are present in
mitochondrial matrix except succinate
dehydrogenase which is tightly bound to inner
mitochondrial membrane
Dr. Hani Alrefai 04/11/2014
- Isocitrate → α-ketogluterate 3 ATP
- α-ketogluterate → succinyl COA. 3 ATP
- Succinyl CoA → succinate 1 ATP
- Succinate → fumarate 2 ATP
- Malate → O.A.A. 3 ATP
12 ATP
Energy production from oxidation of acetyl CoA in Kreb's cycle is 12 ATP.
Total energy production from oxidation of pyruvic a. is 15 ATP.
Energy production from oxidation of glucose to CO2 + H2O + energy is 36 or 38 ATP : 6 or 8 ATP in glycolysis.
6 ATP from conversion of Pyruvic to acetyl COA
24 ATP for acetyl CoA in Kreb's cycle.
Dr. Hani Alrefai 04/11/2014
1-It is the final pathway for complete oxidation
of all food-stuffs CHO, lipids and protein
which are converted to acetyl CoA.
2. It is the major source of energy for cells
except cells without mitochondria as RBCs.
3-It is the major source of succinyl CoA which
used for:
Porphyrine and HB synthesis.
Ketone bodies activation.
Converted to OAA → glucose.
Detoxication by conjugation.
Dr. Hani Alrefai 04/11/2014
4. Synthetic functions of Kreb's cycle: a- Amphibolic reactions.
- In fasting oxaloacetic acid is used for synthesis of glucose by gluconeogenesis.
- In feeding state: citric acid is used for synthesis of fatty acids.
- Reactions of Kreb's cycle are used for synthesis of amino acid as O.A.A. →Aspartic acid and α-ketogluterate → glutemic acid
b- Anaplerotic reactions
- O.A.A. can synthesized from pyruvic acid by pyruvate carboxyalse which used in gluconeogenesis.
- Aspartic acid. → O.A.A.
- Glutamic acid → α-ketogluterate
Dr. Hani Alrefai 04/11/2014
1) Flouro-acetate reacts with oxalacetate
forming flourocitrate, which inhibits the
aconitase enzyme.
2) Arsenite inhibits α-ketoglutarate
dehydrogenase.
3) Malonate acts as competitive inhibitor for
succinate dehydrogenase.
Dr. Hani Alrefai 04/11/2014
Roles of vitamins in citric acid cycle:
1. Riboflavin, the form of FAD , cofactor in ketoglutarate dehydrogenase complex and in succinate dehydrogenase
2. Niacin in the form of NAD, the coenzyme for isocitrate dehydrogenase ,α-ketoglutarate dehydrogenase and malate dehydrogenase
3. Thiamine : as TPP the coenzyme for decarboxylation in α-ketoglutarate dehydrogenase
4. Pantothenic acid as part of coenzyme A which present in the form of acetyl-COA and succinyl -COA
Dr. Hani Alrefai 04/11/2014