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
3

Course Overview
Lipid Metabolism

Carbohydrate Metabolism

Sugars, Starches, Digestion, Absorption, Energy

Amino Acids and Proteins

Production, Breakdown

Digestion, Absorption, Transport, Mobilization

Production, Breakdown, Conversion

Nucleic Acids, DNA and RNA

Medical Genetics

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

Anabolism Catabolism Conversion into derivatives

e.g histidine to histamine Tyrosine to thyroxines Tyrosine to melanin Choline to acetylcholine

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

Products from one provide substrates for the other.

Anabolism and catabolism share many intermediates.

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

FOOD

Proteins
Amino acids

Carbohydrates

Fats
Fatty acids and glycerol

Glucose Glycolysis

Pyruvate
Acetyl CoA
Krebs (Citric acid) cycle

Oxidative phosphorylation

Example is aflatoxin (B1,B2,G1,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], vomitoxin, bovarison

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

17

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

18

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.

Compartmentation of Metabolism Certain metabolic pathways are compartmentalized in different cell sites.

Glycolysis occurs in the cytosol. The Krebs cycle reactions occur in the mitochondrial matrix. Other oxidative reactions occur in the microsomes. In photosynthesis, some pathways are in the chloroplast.

* 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

Let us take the case of the glycolytic pathway, which has several enzymecatalysed steps:

From Stryer

From Matthews & van Holde.

As can be seen, some reactions of glycolysis require an input of energy, whereas others release it. Thus by coupling unfavorable reactions to reactions that can go spontaneously, desired biomolecules can be synthesised without flouting the laws of thermodynamics.

Since many of the effective units of metabolism are the metabolic pathways, how are they controlled?
Let us go back to look at a simple reaction catalysed by a Michaelis-Menten enzyme.

Vmax is the maximum velocity which the amount of enzyme used here can achieve.

Vmax.[S] Vo = K + [S] M

[S] is the concentration of substrate being varied here.

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

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

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

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

Aerobic respiration and fermentation both begin with glycolysis, which converts one molecule of glucose into two molecules of pyruvate After glycolysis, the two pathways diverge
Fermentation is completed in the cytoplasm, 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

Three stages
Glycolysis (carried out in cytoplasm; 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

Typically, 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

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

Glycolysis is the first stage of fermentation

Forms 2 pyruvate, 2 NADH, and 2 ATP

Pyruvate is converted to other molecules, but is not fully broken down to CO2 and water
Regenerates NAD+ but doesnt 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 ethanol

Lactate fermentation
Pyruvate receives electrons and hydrogen from NADH, forming NAD+ and lactate

Fermentation gives rise to doughs by CO2 release.

Fig. 8-10b, p. 133

Yeast powers the fermentation of alcohol making and baking

Fig. 8-10c, p. 133

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

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

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

Its a constant balancing act

When blood glucose concentration rises, the pancreas increases insulin secretion
Cells take up glucose faster, more ATP is formed, glycogen and fatty-acid production increases

When blood glucose concentration falls, the pancreas increases glucagon secretion
Stored glycogen is converted to glucose

About 78% of an adults 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, fatty acid breakdown yields more ATP per carbon atom

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

Biochemical research has impact on nutrition and preventive medicine

all disease has a biochemical basis
51

(1)Physical agent:
mechanical trauma,extremes of temperature, sudden changes in atmospheric pressure, radiation, electric shock

(2)Chemical agents: drugs, certain toxic compounds, therapeutic drugs

52

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

(6) Immunology reaction:Anaphylaxis,

Autoimmune disease

(7) Nutritional imbalances:Deficiencies,excesses

(8) Endocrine imbalances :hormonal deficiencies, hormonal excesses

54

Biochemical studies contribute to diagnosis, prognosis & treatment

Disease
Scurvy Rickets

Causes
deficiencies of vitamin C deficiencies of vitamin D

Arteriosclerosis genetic,dietary environment factors Phenylketonuria mainly mutation the gene coding phenylalanine hydroxylase
55

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

Many biochemical studies illuminate disease mechanisms & disease inspire biochemical research
Use
1.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

Use 2.to reveal the fundamental causes &mechanisms of diseases 3. to suggest rational treatment of diseases

example demonstration of the genetic defects in Cystic Fibrosis.

use of a diet low in Phenylalanine for the treatment of phenylketonuria

4. to assist in the diagnosis of specific disease

use of the plasma enzyme CK-MB in the diagnosis 0f Myocardial Infarction.

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