Bio l4,5

Dr. Hani Alrefai 04/11/2014

Dr. Hani Alrefai

04/11/2014


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.


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.


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+.


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.


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:


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.


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.


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 .


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.


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.


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.


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


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

11/11/2014


Regulation of Glycolysis

Carbon sources of gluconeogenesis

Cori cycle

Krebs cycle

Energy production of glucose oxidation


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.



Glucokinase/

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


Enzymatic:

Hexokinase

Glucokinase

PFK

PK

Hormonal:

Glucagon

cAMP

Represion of Key

reg. enzymes

Insulin

Phosphatase

cAMP

Induction of Key

reg. enzymes


Regulations:

1. Iodoacetate:

inhibits glyceraldehyde-3-P dehydrogenase

2. Fluoride:

inhibits enolase


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


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)


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.


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.


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.


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)


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



Pyruvate

FA oxid.

- 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.


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.


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


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.


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


Bio l4,5

Education

Transcript of Bio l4,5