Seminar Glucose Metabolism

8/6/2019 Seminar Glucose Metabolism

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SEMINAR ON METABOLISM OF CARBOHYDRATES

By Dr. Kshitij Chaurasia

CONTENTS

Definition

Metabolism

Free Energy

Carbohydrates

Classification

Glycolysis

Kreb’s cycle

Electron Transport Chain

Symmary of ATP production

Lactose fermentation

Metabolism of Lactic acid

Cori’s cycle

Glycogenesis and Glycogenolysis

Lipolysis and Lipogenesis

Protein metabolism

Metabolic disorders

Definitions:

Catabolism = the breakdown of complex substances.

Anabolism = the synthesis of complex substances from simpler ones.

Metabolism

Metabolism = Anabolism + Catabolism

EXAMPLE

Photosynthesis requires Respiration

Respiration requires Photosynthesis



Energy Production = Energy Consumption

Free Energy Changes in Metabolism

Overall ∆ G is negative (-) for catabolic processes example:

AÚBDCÚDÚE

higher energy lower

compound G1 energy compound G2

Carbohydrates



A carbohydrate is an organic compound with Aldehyde group attached to carbon

chain with hydroxyl groups

General formula Cn(H2O)n

Synonym of saccharide

Main source of energy for body

Complex carbohydrates (starches) are found in bread, cereal, flour, pasta, nuts, and potatoes

Simple carbohydrates (sugars) are found in soft drinks, candy, fruit, and ice cream

Major pathways of Carbohydrate metabolism begin or end with glucose

Glucose is the molecule ultimately used by body cells to make ATP

Neurons and RBCs rely almost entirely upon glucose to supply their energy needs

The minimum amount of carbohydrates needed to maintain adequate blood glucose

levels is 100 grams per day

Excess glucose is converted to glycogen or fat and stored.

Classification of carbohydrates

Stages of Metabolism

Monosaccharides Disaccharides Polysaccharides

Glucose Sucrose Starch

Glactose Maltose Glycogen

Fructose Lactose Cellulose

Ribose

Glyceraldehyde



Digestion of Carbohydrates

Monosaccharides

◦ Do not need hydrolysis before absorption

◦ Very little (if any) in most feeds

Di- and poly-saccharides

◦ Relatively large molecules

◦ Must be hydrolyzed prior to absorption

◦ Hydrolyzed to monosaccharides

◦ Only monosaccharides can be absorbed

Carbohydrate Digestion

Mouth

Salivary amylase breaks starches down to maltose.

Plays only a small role in breakdown because of the short time food is in the

mouth

Ruminants do not have this enzyme

Digestion in Small Intestine

Pancreas Pancreatic amylase hydrolyzes alpha 1-4 linkages

Produces monosaccharides, disaccharides and polysaccharides

Major importance in hydrolyzing starch and glycogen to maltose

Polysaccharides Disaccharides

Digestion in Small Intestine Digestion mediated by enzymes synthesized by cells lining the small intestine (brush

border)

AMYLAS

Brushbord



Disaccharides Monosaccharides

Exception is β-1,4 bonds in cellulose

Sucrose Glucose + Fructose

Maltose Glucose + Glucose

Lactose Glucose + Glactose

Overview Carbohydrate Digestion

Carbohydrate Metabolism

Since all carbohydrates are transformed into glucose, it is essentially glucose

metabolism

Oxidation of glucose is shown by the overall reaction:

C6H12O6 + 6O2 à 6H2O + 6CO2 + 36 ATP + heat

Glucose is catabolized in three pathways

◦ Glycolysis

◦ Krebs cycle

◦ The electron transport chain and oxidative phosphorylation

Cellular respiration

Glycolysis: cytosol; degrades glucose into pyruvate

Kreb’s Cycle: mitochondrial matrix; pyruvate into carbon dioxide

Electron Transport Chain: inner membrane of mitochondrion; electrons passed to

oxygen

Overview of Glycolysis

sucrase

maltase

lactase



The Embden-Meyerhof (Warburg) Pathway was discovered by Hans Buchner and

Eduard Buchner when sucrose was found rapidly fermented into alcohol by yeast;

Essentially all cells carry out glycolysis

Enzyme driven

Site of glycolysis is in cytosol

Ten reactions - same in all cells - but rates differ

Two phases:

◦ First phase converts glucose to Bishydroxyacetone phosphate and

Glyceraldehyde 3-phosphate

◦ Second phase produces two pyruvates

Products are pyruvate, ATP and NADH

Possible fates for pyruvate

Pyruvic acid:

◦ Moves on to the Krebs cycle in an aerobic pathway

◦ Is reduced to lactic acid in an anaerobic environment

Glycolysis

Glycolysis: Phases

Phase 1: Sugar activation

◦ Two ATP molecules activate glucose into

fructose-1,6-diphosphate

Phase 2: Sugar cleavage

◦ Fructose-1,6-bisphosphate is cleaved into two

3-carbon isomers Bishydroxyacetone phosphate



Glyceraldehyde 3-phosphate

Phase 3: Oxidation and ATP formation

◦ The 3-carbon sugars are oxidized (reducing NAD+)

◦ Inorganic phosphate groups (Pi) are attached to each oxidized fragment

◦ The terminal phosphates are cleaved and captured by ADP to form four ATP

molecules.◦ The final products are:

Two pyruvic acid molecules

Two NADH + H+ molecules (reduced NAD+)

A net gain of two ATP molecules

Krebs Cycle: Preparatory Step

Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids

Pyruvic acid is converted to acetyl CoA

◦ Decarboxylation Carbon is removed from pyruvic acid

Carbon dioxide is released

◦ Oxidation

Hydrogen atoms are removed from pyruvic acid

NAD+ is reduced to NADH + H+

◦ Formation of acetyl CoA – the resulting acetic acid is combined with

coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA

Krebs Cycle

An eight-step cycle in which each acetic acid is decarboxylated and oxidized,

generating:

◦ Three molecules of NADH + H+

◦ One molecule of FADH2

◦ Two molecules of CO2

◦ One molecule of ATP

For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter

the Krebs cycle



Electron Transport Chain

Food (glucose) is oxidized and the released hydrogens:

◦ Are transported by coenzymes NADH and FADH2

◦ Enter a chain of proteins bound to metal atoms (cofactors)

◦ Combine with molecular oxygen to form water ◦ Release energy

The energy released is harnessed to attach inorganic phosphate groups (Pi) to ADP,

making ATP by oxidative phosphorylation

Mechanism of Oxidative Phosphorylation

The hydrogens delivered to the chain are split into protons (H+) and electrons

◦ The protons are pumped across the inner mitochondrial membrane by:

NADH dehydrogenase (FMN, Fe-S)

Cytochrome b-c1 Cytochrome oxidase (a-a3)

◦ The electrons are shuttled from one acceptor to the next

Electrons are delivered to oxygen, forming oxygen ions

Oxygen ions attract H+ to form water

H+ pumped to the intermembrane space:

◦ Diffuses back to the matrix via ATP synthase

◦ Releases energy to make ATP

Mechanism of Oxidative Phosphorylation

ATP Synthetase



The enzyme consists of three parts: a rotor, a knob, and a rod

Current created by H+ causes the rotor and rod to rotate

This rotation activates catalytic sites in the knob where ADP and P i are combined to

make ATP

Summary of ATP Production

LACTOSE FERMENTATION

Anaerobic pathway

Occurs in reduced supply of oxygen

METABOLISM OF LACTIC ACID

Oxidation:

to pyruvate by well oxygenated muscle cells which is then directly used to fuel

the Krebs cycle,

Conversion: to glucose via gluconeogenesis in the liver and release back into the

circulation, (Cori cycle).

CORI’S CYCLE



Glycogenesis and Glycogenolysis

Glycogenesis – formation of glycogen when glucose supplies exceed cellular need for

ATP synthesis

Glycogenolysis – breakdown of glycogen in response to low blood glucose

Gluconeogenesis

The process of forming sugar from noncarbohydrate molecules

Takes place mainly in the liver

Protects the body, especially the brain, from the damaging effects of hypoglycemia by

ensuring ATP synthesis can continue

LIPOLYSIS

LIPOGENESIS



PROTEIN METABOLISM

METABOLISM DISORDERS

What is a metabolic disease? “Inborn errors of metabolism”

“any disease originating in our chemical individuality”

inborn error : an inherited (i.e. genetic) disorder

metabolism : chemical or physical changes undergone by substances in a biological

system

What is a metabolic disease?

Garrod’s hypothesis

A B C (product)

deficiency

substrate excess

D toxic metabolite

Classification:

Small molecule disease

◦ Carbohydrate

◦ Protein

◦ Lipid

◦ Nucleic Acids

Organelle disease



◦ Lysosomes

◦ Mitochondria

◦ Peroxisomes

◦ Cytoplasm

G6-PD DEFICIENCY

G6PD is one of many enzymes that help the body process carbohydrates and turn

them into energy

G6PD also protects red blood cells from potentially harmful byproducts that can

accumulate when a person takes certain medications or when the body is fighting an

infection.

Without enough G6PD to protect them, RBCs can be damaged or destroyed.

G6PD deficiency is an X linked inherited condition.

This deficiency can cause hemolytic anemia, usually after exposure to certain

medications, foods, or even infections. Normally don't have any symptoms

Symptoms disappear once the cause, or trigger, is removed

Rarely leads to chronic anaemia.

With right precautions patient can lead healthy life.

Pyruvate kinase (PK) deficiency:

This is the next most common red cell enzymopathy after G6PD deficiency, but is

rare.

It is inherited in a autosomal recessive pattern and is the commonest cause of the so-

called "congenital non-spherocytic haemolytic anaemias" (CNSHA).

PK catalyses the conversion of phosphoenolpyruvate to pyruvate with the generation

of ATP.

Inadequate ATP generation leads to premature red cell death.

CLINICAL FEATURES

Most patients are anaemic or jaundiced in childhood.

Gallstones, splenomegaly, aplastic crises and skeletal deformities due to marrow

expansion may occur.

Individuals who are most severely affected may die in utero of anemia or may require

blood transfusions or splenectomy.

TREATMENT

Most affected individuals do not require treatment.

Treatment can include a blood transfusion or removal of the spleen. Treatment is

usually effective in reducing the severity of the symptoms.

Glycogen storage disease (Glycogenoses)



CLINICAL FEATURES

Impairs the ability of the liver to produce free glucose from glycogen and from

gluconeogenesis

Some neonates die at first year of life while others have asymtomatic disease

Enlarged liver.

Hyperlipidaemia

Hypoglycaemia

Muscle weakness, myopathy, Exercise intolerance and cramps.

Growth failure

Heart failure

Renal failure

Heamolytic anaemia

Disorder Affected Tissue

Type 0 Liver

Type IA Liver, kidney,intestine

Type IB Liver

CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROMES (CDGS)

Autosome recessive disorders characterised by disorder in glycosylation.

Clinical features- hypoglycaemia, vomiting , diarrhea, hepatic fibrosis, retinopathy

and recurrent thrombosis.

No treatment

REFERENCES

Wikipaedia Text book of biochemistry by Thomas M. Devlin

http://www.unisanet.unisa.edu.au/08366/timages/aametab.gif

http://www.metabolic-database.com/html/lipogenesis_main_page.html

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qoVm8zaO_qir0=&h=604&w=383&sz=19&hl=en&start=17&um=1&itbs=1&tbnid=

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http://www.pathologyportal.org/97th/pdf/companion22h03.pdf

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http://www.pathologyportal.org/97th/pdf/companion22h03.pdf

http://emedicine.medscape.com/article/125096-overview

http://kidshealth.org/parent/general/aches/g6pd.html

Documents

Seminar Glucose Metabolism