Metabolism introduction

$**Metabolism**$ is classified into two aspects: anabolism and catabolism.

1. $Anabolism$: all the biosynthetic pathways which are concerned with %%synthesis of macromolecules%% e.g. glycogen, proteins, lipids

• endergonic
• require energy (mainly supplied by ATP)

1. $Catabolism$: all degradative process whereby complex molecules are %%broken into simpler compounds%%.

Electron Transport Chain (ETC) (Respiratory Chain)

$**ETC**$: formed of a %%series of electron carriers%%, which catalyze the transfer of electrons from reduced coenzymes to oxygen to %%form H2O%%. Part of the energy released during redox reactions is utilized for %%synthesis of high energy phosphate bonds%% (conversion of ADP and Pi to ATP)

Site: ==inner mitochondrial membrane==

Components of ETC

1. Complex I (NADH Dehydrogenase Complex):

• many polypeptides
• @@FMN@@
• seven-iron sulfur centers (@@FeS@@)
• transfer of electrons from NADH to CoQ to form @@CoQH2@@

1. Complex II (Succinate Dehydrogenase Complex):
   • succinate dehydrogenase enzyme
   • FAD
   • two iron sulfur centers (@@FeS@@)
   • transfer of electrons or hydrogens from succuinate to CoQ to form @@CoQH2@@
2. Complex III (Cytochrom bc1 Complex):
   • cytochrome b
   • one @@FeS@@ center
   • cytochrome C1
   • transfer of electrons from CoQH2 to @@cytochrome c@@ with the %%release of two protons (2H+)%%
3. Complex IV (Cytochrome Oxidase):
   • two cytochromes (a, a3)
   • two atoms of @@copper@@
   • transfer of electrons from cytochrome c to oxygen, which combines with two H+ to form H2O
4. Complex V (ATP synthase)
   • inner mitochondrial membrane
   • ^^synthesis of ATP^^ from ADP and Pi
   • main subunits:
     • F0: gate/ channel for protons
     • F1: synthesis of ATP from ADP and Pi. 3 alpha, 3 beta, one gamma subunits (gamma subunits rotates)

Inhibitors of ETC

1. %%Barbiturates%% inhibits complex I (NADH dehydrogenase)
2. %%Carboxin%% inhibits complex II (succinate dehydrogenase)
3. %%Antimycin A and dimercaprol%% inhibits complex III
4. %%H2S, CO and cyanide%% inhibit complex IV (cytochrome oxidase)
5. %%Oligomycin%% inhibits complex V (ATP synthase)

$**Uncouplers**$ in ETC: increase permeability of the inner mitochondrial membrane to protons

e.g. 2,4-dinitrophenol

Tricarboxylic Acid (TCA) Cycle

• $Citric acid cycle$: series of biochemical reactions that are responsible for %%complete oxidation of the acetyl residue.%%
• ^^final common metabolic pathway^^ for oxidation of carbohydrates, fats, and proteins (amino acids)
• @@1 mole acetyl-CoA = 12 moles of ATP@@

Site: mainly in the mitochondria, except succinate dehydrogenase (inner mitochondrial membrane)

==Production==: 2 molecules of CO2, 3 molecules of NADH, 1 molecule of FADH2, 1 molecule of ATP

Only source of ATP a synthesis under anaerobic condition: $glycolysis$

Disorders of carbohydrate digestion

1. Inherited ==lactase deficiency==
2. Inherited ==sucrase deficiency==

$GLUT-1:$ red blood cells $GLUT-2:$ liver, kidneys, pancreatic B cells, lateral border of small intestine, for rapid uptake and release of glucose

• B-cells: secretion of insulin
• Glucose homeostat: liver, kidney

$GLUT-3:$ brain

$GLUT-4:$ heart, skeletal muscles and adipose tissues, insulin stimulated/ dependent

• Translocation of glucose transporters
• No insulin = transporters are endocytosed, form intracellular pool, glucose uptake reduced

$GLUT-5:$ small intestine, kidneys, sodium-dependent

Oxidation of glucose

A. Major pathways for oxidation: %%energy production%%

1. Glycolysis: @@pyruvate@@ under aerobic condition and @@lactate@@ under anaerobic condition
2. Citric acid cycle (Kreb’s cycle): aerobic condition, pyruvate to @@active acetate@@ for oxidation through citric acid cycle

B. Minor pathways for oxidation: %%synthesis of other glucose derivative%%, not energy production

1. Hexose monophosphate pathway ( HMP): production of @@pentoses and NADPH@@
2. Uronic acid pathway: production of @@uronic acids@@