Major metabolic pathways of glucose 10. Foundation Block/Team Work... · *G6PD *Lactonase *6PGD...
Transcript of Major metabolic pathways of glucose 10. Foundation Block/Team Work... · *G6PD *Lactonase *6PGD...
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Major metabolic pathways of glucose
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10
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objectivesDefine a metabolic pathway.
Describe the general metabolic pathways for glucose ( production and utilization ).
Briefly describe the HMP.
Recognize the mechanisms of glucose transport.
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Metabolic pathway➔ Definition:
➔ Site:
a sequence or a cascade of chemical reactions which results in a product that will be a substrate for other reaction.Usually 1 to 2 pathways.
● Cellular (Tissue): signaling between cells.
● Subcellular: reactions inside the cell.
➔ Reactions:
Rate-limiting enzymes.
➔ Regulatory Mechanisim(s):
(Enzymes that slow down the reaction)
Rapid, short-term. Slow, long-term.
Covalent modification.
Allosteric Induction Repression
This slide is not that important
“Usually hormones”
e.g. insulin e.g. glucose A molecule that can bind noncovalently at a site other
than the active site of an enzyme and affect its
activities “either activation or inhibition” without being involved in the reaction.
e.g. Moving phosphate group is adding phosphate group
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Metabolic pathways of glucose ( Production and utilization )
Production
Hexose interconversion
Gluconeogenesis
Glycogenolysis
Utilization
One glycogen gives 2 glucose molecules.
Production of glucose of non-carbohydrate substrates.
How to get glucose molecules?
The conversion between 2 hexoses which is aided by specific enzymes “epimerase-isomerase”.
6 carbon sugar —> 6 carbon sugarE.x. Fructose to glucose.
Hexose interconversion
6 carbon sugar —> 6 carbon sugar
E.x. Glucose to fructose.
HMP/PPP
Glycogenesis
Glycolysis
Krebs cycle
االستفاده من الجلوكوز*
*The most important
HMP : Hexose monophosphate pathwayPPP : pentose phosphate pathway
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Metabolic pathways of glucose catabolic and anabolicCatabolic cycles Anabolic cycles
● Gluconeogenesis.● Glycogenesis.
Glycolysis
➔ Oxidation of glucose to provide energy.
➔ Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen-aerobic glycolysis.
➔ In absence of oxygen and in cells that lack mitochondria, the end product is lactate-anaerobic glycolysis.
● Glycolysis. (Mainly)● Krebs cycle. (Mainly)● Glycogenolysis.● HMP.
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Glycogenesis and glycogenolysisGlycogenesis
➔ Synthesis of glycogen from glucose. Mainly liver, muscles, and cytosol.
Glycogenolysis
➔ Degradation of glycogen into glucose. Mainly liver, muscles, and cytosol.
Gluconeogenesis
➔ Synthesis of glucose from non-carbohydrate precursors.
➔ The precursors could be pyruvate, lactate, glycerol, and alpha-keto acid.
➔ It requires both mitochondria and cytosolic enzymes.
➔ Liver (mainly) , kidney.
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Hexose monophosphate shunt (hmp) / pentose phosphate pathway (ppp)➔ HMP shunt is an alternative pathway of glucose oxidation. The major pathway is glycolysis.
➔ It is not involved in the generation of energy.
➔ Around 10% of glucose is entered in this pathway.
➔ In liver and kidney, this percentage is up to 30%.
Biomedical importanceIt has two main functions:
1. Provides NADPH which is required for:
● Synthesis of fatty acid, steroids, and amino acids.● Detoxification of drugs, cytochrome P450.
● In scavenging the free radicals.1.2. Provides pentoses. Pentose and its derivatives
are useful in the synthesis of: Nucleic acids (DNA and RNA) + Nucleotides (ATP, NAD, FAD, CoA)
Note : NADH : in the electron transport chain as energy molecule .NADPH : cofactor in the glutathione system
The most important pentose is ribose.
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Tissue distribution ➔ Liver.
➔ Lactating mammary gland.
➔ Gonads.
➔ Adrenal cortex.
➔ Adipose tissue.
➔ Lens and cornea.
➔ Erythrocytes to reduce glutathione.
Phases of HMP shunt
● Oxidative phase
● Non-oxidative phase
The cytosol of:
Glucose NAD+ NADPH Oxygenation
+
It has two phases:
Oxidative phase:-produce NADPH -Irreversible
•Non-oxidative phase:-produce pentose- reversible
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Main enzymes
HMP Shunt
Non-Oxidative OxidativeNADP+ NADPH
Dehydrogenase
Hydrolase
Transaldolasetransfers 3 carbons
Main outcomes
TransketolaseTransfers 2 carbons
Phases
NADPH
RiboseFor DNA,NAD,etc
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Phases :-O
XID
ITIV
E
Dehydrogenase
Hydrolase
Note : in oxidative phase
1 Glucose 2 NADPH
NO
N –
O
XID
ATI
VE
Isomerase
epimerase
Trnasketolase
Transaldolase
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Oxidative PhaseIrreversible
*G6PD
*Lactonase
*6PGD
Glucose-6-phosphate dehydrogenase (G6PD): G6P is oxidized to 6-phosphogluconolactone with reduction of NADP+ to NADPH
Lactonase: The lactone ring is then oxidized to form 6-phosphogluconic acid
6-Phosphogluconate dehydrogenase: 6-Phosphogluconate is oxidatively decarboxylated to yield ribulose 5-phosphate (Rbl5P), CO2 and another NADPH
*Glucose -6-phosphate dehydrogenase
*6-phosphogluconolacton hydrolase
*6-phosphogluconate dehydrogenase
Names of enzymes you have to memorize it
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Non-Oxidative PhaseReversible
Names of enzymes you have to memorize it
*phosphopentose epimerase*phophopentose isomerase
D-Ribose-1-P
D-Ribose-1,5-di-P*Transketolase
*Transketolase
*Transaldolase
TPP *Thiamine pyrophosphate “ cofactor “
Fructose-6-phosphate
TPP
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Clinical correlations
G-6-PDDeficiency results in Hemolytic
anemia
Kidney failure
Neonatal jaundice
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Glucose Transport Na+-Monosaccharide Cotransporter :
Against concentration gradient
Energy dependent
Carrier-mediated
Coupled to Na+ transport
Small intestine, renal tubules & choroid plexus
Na+-Independent Facilitated Diffusion:Transport only 1 molecule of Glucose each time
Down the concentration gradient
Energy Independent
Glucose Transporters (GLUT 1-14)
*From low to high
*From high to low
*doesn’t require energy
* requires energy
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Transporter Location Function
GLUT-1 Blood (RBCs )& Brain & ( baby ) fetus
Glucose uptake from blood
GULT-2(Gluconeogenesis for maintain
Homeostasis)
Liver , Kidney & Pancreas Blood & cells (either direction )
GULT-3 Neurons & Placenta & kidney
Glucose uptake from blood
GULT-4(Insulin dependent)
Adipose tissues ( fat ) & skeletal muscles
Glucose uptake from blood
GULT-5 Small intestine & testes Fructose transport
GULT-7 Liver ( ER – membrane ) —
Glucose Transporters Function نحفظ المتشابھ عشان یسھل الباقيال
BBB
Kids Lips
Pink
Mother Father
BBB kids lips are pink mother father
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Take home messageThere are multiple pathways for glucose that can be grouped in to catabolic (utilizing glucose) or anabolic (producing glucose)
Glycolysis is the major metabolic pathway of glucose breakdown to provide energy
Alternative pathway for glucose oxidation but not meant for producing energy
Has two phases- oxidative and non-oxidative
During oxidative phase, glucose-6-P is oxidized with generation of 2 moles of NADPH, and one mole of pentose phosphate, with liberation of CO2
During non-oxidative phase, pentose phosphate is converted to intermediates of glycolysis
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Quiz Q1: The metabolic pathway of HMP shunt is:
A) Catabolic B) Glycogenesis C) Gluconeogenesis D) Anabolic
Q2::The end product of aerobic glycolysis is
A) Glycerol B) glucose-6-phosphate C) pyruvate D) lactate
Q3:The conversion of ribulose-5-phosphate into ribose-5-phosphate is aided by:
A) Ribose-5-phosphate dehydrogenase
B) glucose-6-phosphate dehydrogenase
C) transketolose D) isomerase
Q4: The end product of the oxidative phase of HMP pathway is:
A) Glyceraldehyde-3-phosphate
B) ribulose-5-phosphate C) xylulose-5-phosphate D) glucose
Q1 :what is the molecule responsible for Fructose transportation and in what organ is it located ?
Q2 :what is the final product of the oxidative phase of HMP shunt ?
MCQs SAQ
1)A2)C3)D4)B
MCQs answers
SAQ answer:
Q1:GULT-5 & it’s in small intestine and testesQ2:Ribulose-5-phosphate
For extra MCQs and SAQs, Click Here
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Team members
Team leaders
Girls Team : Boys Team :● Alia Zawawi ● Nada Babilli● Rania Aqil● Reem alamri ● Reema Alomar● Reem Alqahtani● Renad Alhumaidi● Samar Almohammedi ● Shaden Alobaid● Budoor Almubarak● Somow Abdulrahman● Noura Alsalem● Lama Alahmadi● Sadem Alhazmi
● Mansour albawardi● Hassan alshurafa● Abdulrahman almebki● Mohammed alsayyari● Abdullaziz alomar● Ahmed Alkhayat● Abdulaziz alrabiah● Saud alrasheed● abdullah almazroo● Hamad almousa
● Shatha Aldhohair ● Mishal AlthunianMade by :
● Nuha Alkudsi● Norah Alsheikh● Muneerah Alssdhan● Mayasem Alhazmi