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Edited by Dr.Liniyanti D Oswari, MNS,MSc.

What is biochemistry?
“Living things are composed of lifeless molecules. When these molecules are isolated and examined individually, they conform to all the physical and chemical laws that describe the behavior of inanimate matter.”
-Albert Lehninger (1917-1986)

Science concerned with chemical basis of life in Human being.  Science concerned with the chemical constituents of living cells and with the reaction and process that they undergo
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DNA and RNA  Medical Genetics . Course Overview ◦ Lipid Metabolism ◦ Carbohydrate Metabolism  Sugars. Mobilization  Production. Absorption. Energy ◦ Amino Acids and Proteins  Production. Absorption. Breakdown  Digestion. Conversion ◦ Nucleic Acids. Breakdown. Digestion. Starches. Transport.

and which are fundamental to life. Concise Encyclopedia of Biochemistry .Metabolism: the sum total of chemical (and physical) changes that occur in living organisms.

g histidine to histamine Tyrosine to thyroxines Tyrosine to melanin Choline to acetylcholine .   Anabolism Catabolism Conversion into derivatives ◦ ◦ ◦ ◦ e.

Catabolism: exergonic oxidation (Pemecahan dari molekul kebesar ke molekul lebih kecil contoh Sukrosa dg enzim Sukrase jadi Glukosa & Fruktosa) Anabolism: endergonic biosynthesis (Mensintesa dari molekul kecil kemolekul lebih besar contoh Asam amino memben tuk Protein Otot) .

Metabolism .

) .Proteins Fats Carbohydrates (Nutrients) ADP Catabolism (Oxidation) ATP NADP+ NADPH Intermediates Anabolism (Biosynthesis) Waste (CO2/Urea/etc.

Catabolism degradative Anabolism synthetic oxidative energy producing (exergonic) convergent makes pool molecules produces NADH & NADPH reductive energy requiring (endergonic) divergent uses pool molecules uses NADPH almost exclusively .

Anabolism and catabolism share many intermediates.Products from one provide substrates for the other. .

.The three stages of catabolism. carbon dioxide. and ammonia. Stage 3: Catabolism converges to three principal end products: water. Stage 1: Proteins. polysaccharides. and lipids are broken down into their component building blocks. the acetyl groups of acetyl-CoA. Stage 2: The building blocks are degraded into the common product.

FOOD Proteins Amino acids Carbohydrates Fats Fatty acids and glycerol Glucose Glycolysis Pyruvate Acetyl CoA Krebs (Citric acid) cycle Oxidative phosphorylation .

B2.G1. Example is aflatoxin (B1.G2) ◦ Converted to M1 in liver and P1 in kidney (urine) ◦ Carcinogenic ◦ Negatively affects immune system  Where do they come from? ◦ Molds growing on plant material produce toxins  Other toxins ◦ Fumonison(horses) [10-15-ppm]. bovarison . vomitoxin.

The metabolic activity represented in this diagram must be controlled for the cell/ organism to survive and reproduce. .

Long-Term Regulators Leptin • Secreted by adipocytes in proportion to amount of stored fat • Primary way brain knows how much body fat is stored • Obesity is related to receptor unresponsiveness Insulin • Secreted by beta cells in pancreas • Stimulates glucose & amino acid uptake • Promotes glycogen & fat synthesis • Additional way brain knows how much body fat is stored (effect weaker than leptin) .

Digestion is the first step of catabolism

Carbohydrates Proteins Lipids

glucose, fructose, galactose amino acids glycerol fatty acids

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Substances that connect metabolic pathways In reduction, coenzymes accept H atoms In oxidation, coenzymes remove H atoms FAD (flavin adenine dinucleotide)

FAD + -CH2-CH2-

FADH2 + -CH=CH-

NAD+ (nicotinamide adenine dinucleotide)

NAD+ + -CH-OH

NADH + H+ + -C=O

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Metabolism.
All chemical & physical changes that occur in living organisms appear to obey the “universal laws” of thermodynamics.

Reactions must be thermodynamically possible, even if seemingly unfavorable, for them to occur in biochemistry.

. ◦ In photosynthesis. ◦ Glycolysis occurs in the cytosol. ◦ The Krebs cycle reactions occur in the mitochondrial matrix.Compartmentation of Metabolism  Certain metabolic pathways are compartmentalized in different cell sites. some pathways are in the chloroplast. ◦ Other oxidative reactions occur in the microsomes.

* Biochemistry studies have illuminated many aspects of health & disease * the study of various aspects of health & disease has opened up new areas of biochemistry 21 .

Biochemistry Nucleic acid Protein lipid Carbohydrates Geneticdisease Sickle cell anemia arteriosclerosis Diabetes mellitus Medicine 22 .

which has several enzymecatalysed steps: From Stryer .Let us take the case of the glycolytic pathway.

.From Matthews & van Holde.

As can be seen. Since many of the effective units of metabolism are the metabolic pathways. desired biomolecules can be synthesised without flouting the laws of thermodynamics. how are they controlled? Let us go back to look at a simple reaction catalysed by a Michaelis-Menten enzyme. Thus by coupling unfavorable reactions to reactions that can go spontaneously. whereas others release it. . some reactions of glycolysis require an input of energy.

[S] Vo = K + [S] M [S] is the concentration of substrate being varied here. Vmax. KM is defined as the ratio of the rate constants of the component reactions in the derivation of the rate equation: Enzyme + Substrate  ES complex Enzyme + Product k-1+ k2 KM = k1 E + S  ES  E + P k1 k-1 k2 .Vmax is the maximum velocity which the amount of enzyme used here can achieve.

with some inhibition of pyruvate kinase by ATP in some tissues. .The control of glycolysis occurs mainly at PFK1.

etc. fatty acid synthesis and breakdown. From Matthews & van Holde . such as glycogen synthesis and breakdown.The full picture of the control of glycolysis naturally involves input from metabolically related pathways.

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 Aerobic respiration ◦ Aerobic metabolic pathways (using oxygen) are used by most eukaryotic cells  Fermentation ◦ Anaerobic metabolic pathways (occur in the absence of oxygen) are used by prokaryotes and protists in anaerobic habitats .

yielding 2 ATP per glucose molecule ◦ Aerobic respiration is completed in mitochondria. yielding 36 ATP per glucose molecule if all processes there go to completion  . which converts one molecule of glucose into two molecules of pyruvate After glycolysis. the two pathways diverge ◦ Fermentation is completed in the cytoplasm. Aerobic respiration and fermentation both begin with glycolysis.

necessary to set stage for mitochondrial processes that follow ◦ Acetyl-CoA formation during Krebs cycle ◦ Electron transfer phosphorylation (ATP formation) C6H12O6 (glucose) + O2 (oxygen) → CO2 (carbon dioxide) + H2O (water) ◦ Coenzymes NADH and FADH2 carry electrons and hydrogen . Three stages ◦ Glycolysis (carried out in cytoplasm.

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the breakdown of one glucose molecule yields 36 ATP for all three stages: ◦ Glycolysis: 2 ATP ◦ Acetyl CoA formation and Krebs cycle: 2 ATP ◦ Electron transfer phosphorylation: 32 ATP . Typically.

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 Fermentation pathways break down carbohydrates without using oxygen The final steps in these pathways regenerate NAD+ but do not produce ATP  .

2 NADH. Glycolysis is the first stage of fermentation ◦ Forms 2 pyruvate. and 2 ATP  Pyruvate is converted to other molecules. but is not fully broken down to CO2 and water ◦ Regenerates NAD+ but doesn’t produce ATP  Provides enough energy for some singlecelled anaerobic species .

 Alcoholic fermentation ◦ Pyruvate is split into acetaldehyde and CO2 ◦ Acetaldehyde receives electrons and hydrogen from NADH. forming NAD+ and lactate . forming NAD+ and ethanol  Lactate fermentation ◦ Pyruvate receives electrons and hydrogen from NADH.

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133 . p. 8-10b.Fermentation gives “rise” to doughs by CO2 release. Fig.

p.Yeast powers the fermentation of alcohol making and baking Fig. 133 . 8-10c.

 Slow-twitch muscle fibers (“red” muscles) make ATP by aerobic respiration ◦ Have many mitochondria ◦ Dominate in prolonged activity  Fast-twitch muscle fibers (“white” muscles) make ATP by lactate fermentation ◦ Have few mitochondria and no myoglobin ◦ Sustain short bursts of activity .

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the net yield of ATP from fermentation is very small   . Fermentation pathways start with glycolysis Substances other than oxygen accept electrons at the end of the pathways Compared with aerobic respiration.

fats and proteins in the diet  . the entrance of glucose and other organic compounds into an energy-releasing pathway depends on the kinds and proportions of carbohydrates. Pathways that break down molecules other than carbohydrates also keep organisms alive In humans and other mammals.

glycogen and fatty-acid production increases   When blood glucose concentration falls. the pancreas increases insulin secretion ◦ Cells take up glucose faster. more ATP is formed. It’s a constant balancing act When blood glucose concentration rises. the pancreas increases glucagon secretion ◦ Stored glycogen is converted to glucose .

fatty acid breakdown yields more ATP per carbon atom . About 78% of an adult’s energy reserves is stored in fat (mostly triglycerides) Enzymes cleave fats into glycerol and fatty acids ◦ Glycerol products enter glycolysis ◦ Fatty acid products enter the Krebs cycle   Compared to carbohydrates.

 Enzymes split dietary proteins into amino acid subunits. which enter the bloodstream ◦ Used to build proteins or other molecules  Excess amino acids are broken down into ammonia (NH3) and various products that can enter the Krebs cycle .

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Biochemical research has impact on nutrition and preventive medicine all disease has a biochemical basis 51 .

(1)Physical agent: mechanical trauma. electric shock (2)Chemical agents: drugs.extremes of temperature. certain toxic compounds. radiation. therapeutic drugs 52 . sudden changes in atmospheric pressure.

Higher forms of parasites (4)Oxygen lack : loss of blood supply.Fungi.(3)Biologic agents: Viruses. molecular 53 . Bacteria. depletion of the oxygen-carrying capacity of the blood. poisoning of the oxidative enzyme (5) Genetic disorders: Congenital .

(6) Immunology reaction:Anaphylaxis. hormonal excesses 54 . Autoimmune disease (7) Nutritional imbalances:Deficiencies.excesses (8) Endocrine imbalances :hormonal deficiencies.

dietary environment factors Phenylketonuria mainly mutation the gene coding phenylalanine hydroxylase 55 . prognosis & treatment Disease Scurvy Rickets Causes deficiencies of vitamin C deficiencies of vitamin D Arteriosclerosis genetic.Biochemical studies contribute to diagnosis.

Disease Cystic fibrosis Cholera Diabetes type I causes mutation in the gene coding the CFTR Protein exotoxin of Vibrio Cholera genetic and environment factors resulting in deficiency of insulin 56 .

To act as screening tests for the early diagnosis of certain diseases example use of measurement of blood tyrosine or TSH in the neonatal diagnosis of congenital hypothyroidism 57 .Many biochemical studies illuminate disease mechanisms & disease inspire biochemical research Use 1.

to suggest rational treatment of diseases example demonstration of the genetic defects in Cystic Fibrosis. to assist in the diagnosis of specific disease use of the plasma enzyme CK-MB in the diagnosis 0f Myocardial Infarction.Use 2.to reveal the fundamental causes &mechanisms of diseases 3. use of a diet low in Phenylalanine for the treatment of phenylketonuria 4. 58 .

Use example 5. the progress of certain disease ALT in monitoring the progress of infectious hepatitis (6. To assist in assessing the use of measurement of response of diseases to therapy blood CEA in certain patients who have been treated for cancer of the colon 59 .