Edited byDr.Liniyanti D Oswari, MNS,MSc.

What is biochemistry?

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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Course OverviewCarbohydrate MetabolismSugars, Starches, Digestion, Absorption, Energy Lipid MetabolismDigestion, Absorption, Transport, MobilizationAmino Acids and ProteinsProduction, Breakdown, ConversionNucleic Acids, DNA and RNAProduction, BreakdownMedical 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

AnabolismCatabolismConversion into derivativese.g histidine to histamineTyrosine to thyroxinesTyrosine to melaninCholine to acetylcholine

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

Metabolism

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.

FOODProteinsCarbohydratesFatsAmino acidsFatty acids and glycerolGlucoseGlycolysisPyruvateAcetyl CoAKrebs (Citric acid) cycleOxidative phosphorylation

Gut-Brain Peptides(only a few out of many)Chemical signals from the G.I. Tract to the Brain

Short-term RegulatorsLast for minutes to hoursMake us want to start eating and stop eating

Long-term RegulatorsWork over periods of weeks to yearsRegulate our caloric intake & energy spent and amount of adipose tissue

Short-Term Regulators

GhrelinSecreted from parietal cells when stomach empty & stops within an hour of eatingProduces sensation of hunger & starts up eatingCauses hypothalamus to release GHRH ( hGH)

Peptide YYSecreted by ileum & colon in response to food in the stomach, in proportion to calories consumedSignals satiety & stops eating

CholecystokininSecreted by duodenum & jejunumProduces appetite-suppressing effect via Vagus N.

Long-Term Regulators

LeptinSecreted by adipocytes in proportion to amount of stored fatPrimary way brain knows how much body fat is storedObesity is related to receptor unresponsiveness

InsulinSecreted by beta cells in pancreasStimulates glucose & amino acid uptakePromotes glycogen & fat synthesisAdditional way brain knows how much body fat is stored (effect weaker than leptin)

*Digestion is the first step of catabolism

Carbohydratesglucose, fructose, galactose

Proteinsamino acids

Lipidsglycerol fatty acids

*Substances that connect metabolic pathwaysIn reduction, coenzymes accept H atomsIn 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

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.

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. Compartmentation of Metabolism

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

*BiochemistryNucleic acidProtein lipidCarbohydratesGeneticdiseaseSickle cell anemiaMedicinearteriosclerosisDiabetes mellitus

From StryerLet us take the case of the glycolytic pathway, which has several enzyme-catalysed steps:

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.[S]KM + [S]Vo =Vmax is the maximum velocity which the amount of enzyme used here can achieve.[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 k2E + S ES E + P k1 k-1+ k2KM = k1

Aerobic respirationAerobic metabolic pathways (using oxygen) are used by most eukaryotic cells

FermentationAnaerobic 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 divergeFermentation is completed in the cytoplasm, yielding 2 ATP per glucose moleculeAerobic respiration is completed in mitochondria, yielding 36 ATP per glucose molecule if all processes there go to completion

Three stagesGlycolysis (carried out in cytoplasm; necessary to set stage for mitochondrial processes that followAcetyl-CoA formation during Krebs cycleElectron 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 fermentationForms 2 pyruvate, 2 NADH, and 2 ATP

Pyruvate is converted to other molecules, but is not fully broken down to CO2 and waterRegenerates NAD+ but doesnt produce ATP

Provides enough energy for some single-celled anaerobic species

Alcoholic fermentationPyruvate is split into acetaldehyde and CO2Acetaldehyde receives electrons and hydrogen from NADH, forming NAD+ and ethanol

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

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

Slow-twitch muscle fibers (red muscles) make ATP by aerobic respirationHave many mitochondriaDominate in prolonged activity

Fast-twitch muscle fibers (white muscles) make ATP by lactate fermentationHave few mitochondria and no myoglobinSustain 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 secretionCells take up glucose faster, more ATP is formed, glycogen and fatty-acid production increases

When blood glucose concentration falls, the pancreas increases glucagon secretionStored 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 acidsGlycerol products enter glycolysisFatty 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 bloodstreamUsed to build proteins or other molecules

Excess amino acids are broken down into ammonia (NH3) and various products that can enter the Krebs cycle

Amino acids are absorbedfrom the small intestine

About 50% from dietAbout 25% from dead epithelial cellsAbout 25% from digested enzymes

1) Amino acids used for protein synthesis

Amino acids can be actively transported into body cells & used to build proteinsWhat are someexamples of proteins?

20 different amino acids are used to synthesize proteins

8 called essential amino acids because they must come from the diet

Histidine & arginine are semi essensial amino acids for adult and essential amino acids for baby.

Foods that contain all the essential amino acids are called complete proteins, for example; eggs, milk, meat.

The nonessential amino acids can be produced by the body through a process called transamination

Transamination = transfer of an amino group (NH2) from an abundant amino acid to a keto acid to make a new amino acid

Keto acid + amino group (NH2) amino acid

2) Amino acids can be used as fuel, or a source of energy

First step is deamination, which is removal of an amino group (NH2) from an amino acid creating a keto acid

Amino acid Keto acid + amino group (NH2)

p 1023Depending on which amino acid is deaminated,

the keto acid may be converted to;Pyruvic acidAcetyl CoAOne of the acids of citric acid cycle

p 1023Pyruvic acid could be converted back into glucose by cells in the kidney or liver

This is an example of gluconeogenesis, which is making glucose from a non-carbohydrate source

p 1023The amino group is transferred to ketoglutaric acid, making glutamic acid, that travels to the liver & is converted back to ketoglutaric acid

Left over ammonia (NH3) is converted to urea

p 1025Absorptive State = 4 hours during & after a mealNutrients are being absorbed & then immediately used or stored

Postabsorptive State = stomach & intestine are emptyStored fuel molecules are used for energy

* Biochemical research has impact on nutrition and preventive medicine

all disease has a biochemical basis

*(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

*(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 enzymeGenetic disorders:Congenital , molecular

*(6) Immunology reaction:Anaphylaxis,Autoimmune disease

(7) Nutritional imbalances:Deficiencies,excesses

(8) Endocrine imbalances :hormonal deficiencies, hormonal excesses

*Biochemical studies contribute to diagnosis, prognosis & treatment

Disease CausesScurvy deficiencies of vitamin CRickets deficiencies of vitamin D

Arteriosclerosis genetic,dietary environment factors

Phenylketonuria mainly mutation the gene coding phenylalanine hydroxylase

* Disease causesCystic fibrosis mutation in the gene coding the CFTR Protein Cholera exotoxin of Vibrio Cholera Diabetes type I genetic and environment factors resulting in deficiency of insulin

*Many biochemical studies illuminate disease mechanisms & disease inspire biochemical research

Use example1.To act as screening use of measurement of blood tests for the early tyrosine or TSH in the diagnosis of certain diseases neonatal diagnosis of congenital hypothyroidism

*Use example2.to reveal the fundamental demonstration of the genetic causes &mechanismsdefects in Cystic Fibrosis. of diseases3. to suggest rational use of a diet low in Phenyl- treatment of diseases alanine for the treatment of phenylketonuria4. to assist in the diagnosis use of the plasma enzyme of specific disease CK-MB in the diagnosis 0f Myocardial Infarction.

*Use example5. the progress of certain ALT in monitoring the disease 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

*****Figure 8.10Alcoholic fermentation in action. (a) A vintner examines a fermentation product of Saccharomyces. (b) A commercial vat of yeast dough rising with the help of yeast cells. (c) Scanning electron micrograph of yeast cells.