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Major metabolic pathways of glucose

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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.

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

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

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.

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.

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.

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

Main enzymes

HMP Shunt

Non-Oxidative OxidativeNADP+ NADPH

Dehydrogenase

Hydrolase

Transaldolasetransfers 3 carbons

Main outcomes

TransketolaseTransfers 2 carbons

Phases

NADPH

RiboseFor DNA,NAD,etc

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

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

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

Clinical correlations

G-6-PDDeficiency results in Hemolytic

anemia

Kidney failure

Neonatal jaundice

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

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

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

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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