Cynthia_tss Blog

food contain lipid transport as chyloromicrons in intestine

undergoes digestion with the aid of bile acid and pancreatic lipase

give fatty acid and glycerol : provide energy, synthesize brain and nerve tissue, energy reserve

activated form of fatty acid is acyl-coA
           oxidation               hydration         
         2nd oxidation          cleavage
acyl-coA -  trans beta-enoyl-coA - beta-hydroxyacl-coA   - beta-ketocyl-coA - acyl-coA

odd number fatty acid - propionyl coA - succinyl coA - krebs cycle

ketone bodies@substances related to acetone produces when an excess of acetyl-coA arises from beta-oxidation

this condition occur when not enough oxaloacetate available to react with large amount of acetyl-coA that could enter citric acid cycle.

occur wif diabetic patiens, starvation(keep fit), high intake lipid low intake carbohydrate

formation of ketone bodies
1 acetyl coA  = acetoacetylcoA = acetoacetate = beta hydroxybutyrate + acetone

biosynthesis of cholesterol

acetyl coA 2C= 3-hydroxyl-3-methylglutaryl-coA ( HMG-CoA)   = mevalonate 6 C =
isoprene isopentenyl pyrophosphate (IPP) 5C= squalene  30C= cholesterol 27C

Chylomicrons 90% triacyglyceride = food, exogenous
lipoprotein = endogenous

VLDL= 60% triacyglyceride
IDL = 40% triacyglyceride
LDL = 50 % cholesterol
HDL = protein 25%  transport cholesterol back to liver

VLDL not mature form = IDL = LDL  mature form

cholesterol can be converted to
manufacture bile acid
precursor of vitamin D
manufacture of steroid hormones

bile acid synthesis is the only mechanism for the elimination of the excess cholesterol
bile acid = emulsifying agent
solubilise cholesterol preventing ppt of cholesterol in gallbladder

hypercholesterolimia : high blood cholesterol

plaque: narrowing of blood vessel  cause blood clot cause stroke or death

avoid , take poly.mono unsaturated oils .
mevastatin & lovastatin = inhibit HMG-CoA reductase
cholestyramine resin = interrupt enterohepatic circulation of bile acid
sitisterol = block absorption of cholesterol from GI tract
probucol = increase LDL catabolism
nicotinic acid = inhibit adipose tissue lipolysis

catabolism: breakdown of molecule to get energy
anabolism: synthesis of compounds needed by the cells

glycogenesis: glucose - glycogen
glycogenolysis: glycogen - glucose

glycolysis: glucose - pyruvic acid
aerobically - pyruvic acid’
Glucose - glucose -6- phosphate - fructose -6- phosphate - fructose 1,6 -biphosphate-
glyceraldehyde-3-phosphate - pyruvate

glucose + 2ADP +  2NAD+  + 2Pi  = 2 PYRUVATE + 2 ATP + 2NADH + 2H+

anaerobically - lactate
anaerobically: glucose + 2ADP + 2Pi = 2 lactate + 2ATP + 2H20

alcoholic fermentation by yeast: glucose +2ADP +2Pi = 2 ethanol + 2CO2 + 2ATP +2H20

gluconeogenesis: all mechanism responsible for converting non carbohydrate for glucose or glycogen
major substance: gluconeogenic amino acids, lactate, glycerol, propionate

it meet the need of body for glucose supply when carbohydrate is not available in sufficient amt from diet

clear the product of metabolism of other tissue from the blood eg lactate, glycerol, propianate

disorder
- fructose-1.6-biphosphatase deficiency cause lactic acidosis
- glycosuria
- hypoglycemia
- type 1 diabetes mellitus

deficiency

von gierke’s disease : deficiency of glucose-6-phosphatase
andersen’s disease : absence of branching enzyme
hers’s disease : deficiency of liver phosphorylase
cori’s disease : absence of debranching enzyme

protein - amino acids - amphibolic pathway :
either undergoes catabolic to give CO2 + H20
OR  anabolic pathway to giv protein, carbohydrate

Transamination
glutamate = alpha-ketoglutarate    NH3+ group replaced by ketone group

muscle generate more than 50 % total pool of amino acids

it release mostly glutamine and alanine to blood

in liver, glucose production from alanine higher than other amino acids
alanine - pyruvate - glucose

aspartate synthesis :  oxaloacetate - aspartate   
by enyzme aspartate aminotransferase

Deamination

oxidative: amino acid to alpha-keto acid
l-glutamate - alpha ketoglutarate    by glutamate dehyrogenase
NAD+   -  NADH

Decarboxylation
tyrosine - tyramine

urea cycle - to avoid ammonia intoxication, synthesised in liver 
transported to kidney for excretion
90% of urinary nitrogen is urea

urea cycle disorder" carbomyl phosphate synthase 1 deficiency" hyperammonaemia type 1
ornithine transcarbamoylase deficiency: hyperammonaemia type ll
citrullinaemia: elevated citrulline levels in urine and plasma

impaired ability to convert phenylalanine to tyrosine
defects in phenylalanine hydroxylase
defects in dihydrobiopterin biosynthesis/reductase ( rare but severe)

alternative metabolite produce ie phenylpyruvic acid cause mental retardation

maple syrup urine disease
reduced of alpha keto acid decarboxylase
maple syrup odour to urine
must remove leu,ile,valine from diet.

albinism : tyrosine hydrolase absent
white hair , pink skin , photophobia coz lack of eye pigment

nearly all product of digestion of carbohydrate , fat and protein are
metabolised to acetyl-coA b4 final oxidation to CO2 in citric acid cycle

amino acids

- lactic acid - acetyl coA - krebs cycle - electron transport chain -ATP

- urea cycle - urea - urine 90%

                                    GLYCOLYSIS
glucose - glucose -6-phosphate  - pyruvid acid - acetyl coA - krebs cycle -
                                   GLUCONEOGENESIS
             electron transport chain - ATP

fatty acid - acetyl coA - krebs cycle - electron transport chain - ATP

Electron transport chain
in mitochondria H removed from substrate by dehydrogenase, donate their E- to ETC which transfer them oxygen reducing it to H20.cytochrome oxidase passes electons to O2 which require 4 H+ to reduce O2 completely to two H20.

ENERGY released in ETC is used for oxidative phosphorylation of ADP to ATP which takes place in the inner mitochondrial membrane.

ETC can be inhibited by
ET inhibitors prevent E- pass from 2 carrier to next carrier/complex
eg: rotenone,antimycin, cyanide, azide anion, malonate
uncoupling agents eg 2,4-DNP, FCPP
oxidative phosphorylation inhibitor : eg oligomycin : bind ATP synthase block proton channel

AA classfied by polarities : polar, non polar, acidic , basic

aliphatic group: alanine, glycine, isleucine, leucine, valine

hydroxyl : serine, threonine

sulphur: cysteine, mathionine

acidic: aspartic acid, asparagine, glutamic acid, glutamine

basic: arginine, histidine, lysine

aromatic: phenylalanine, tyrosine, tryptophan

pI is the midway btw pK values on either side of isoelectric species with net charged 0
isoelectric point: + and - charge equal

acid below pI  COOH remain, NH3+     charge = +1 
base above pI  COOH = COO-    NH3+  = NH2      charge = -1
at isoelectric point charge = 0

essential aa = cannot be synthesised in human , must supplu from diet
leu,lle,lys,trp,met,his,arg,phe,val,thr

non essential aa = can synthesise in body
gly,ala,ser,asn,gln,pro,asp,glu,cys,tyr

dipeptide = 2 aa
tripeptide = 3 aa
tetrapeptide , pentapeptide so on

amino acids link by peptide bond/amide bond to form polypeptide chain

classes of peptides: ribosomal peptides, non ribosomal peptides, digestive peptides

dipeptide eg l-aspartyl-l-phenylalanine  200x sweeter than sugar

tripeptide  eg gamma -glutamyl-l-cysteinylglycine / glutathione it is scavenger for oxidizing agent that are harmful to organism

pentapeptide , 2 pentapeptide found in brain are enkephalins eg leucine and methione enkephalin.natural analgesic

protein: made up of more than 1 polypeptide
functions: carriers, structural, catalytic, defense system, hormones

primary structure: order in which amino acids are linked together
secondary structure: arrangement in space of the atoms in the backbone of the polypeptide chain alpha helix and beta plated sheet hydrogen bonded arrangement are the most important secondary structure
tertirary structure: 3D arrangement of all atoms in protein including side chain and prosthetic group
quaternary structure: arrangement of subunit with respect to one another

alpha helix : rodlike involve only 1 polypeptide chain
beta sheet: H-bond can be formed btw diff part of single chain that is doubled back on itself or btw diff chain

eg collagen

tertiary structure: 3d arrangement of all atoms in molecules.

myoglobin: eg of globular protein
8 alpha helical regions and no pleated sheet regions.

quaternary: consist more than 1 polypeptide chain
eg dimers, trimers, tetramers  eg insulin

as a result of these non covalent interaction subtle changes in structure ar one site on a protein molecule may cause drastic change in properties at a distant site. this property = allosteric

denaturation
pH
heat
detergents eg urea, SDS

Hemoglobin   tetramer : 2 alpha chain 2 beta chain
heme group same in hemoglobin and myoglobin
both bind oxygen reversible

1 molecule of hemoglobin can bind 4 molecules of oxygen
binding of o2 is cooperative in hemoglobin meaning to say, after bind 1st, second o2 is easier to bind.
oxygen binding curve in myoglobin is hyperbolic
hemoglobin is sigmoidal

all enzyme = globular protein
biocatalyst = increase rate of reaction
highly specific to substrate

1.oxidoreductase = redox
2.transferase = group transfer
3.hydrolases = hydrolytic reaction
4.lyases = group to double bonds
5.isomerase = isomerisation
6.ligases = condensation

D-hexose-6-phosphotransferase    2.7.1.1   
2= class of enzyme, 7= subclass, 1= subsubclass,1 = specific enzyme

some enzyme need coenzyme for full activation

lock and key model
substrate and enzyme has complementary shape

induced fit model
shape of active site not exact complementary of shape of substrate
after binding, comformational change in shape of active site

types of catalytic mechanism

nucleophilic substitution , subtance seek positive charge
acid-base catalysis , donation or acceptance of proton
metal ion catalysis, metal ions is electron acceptor and complexed to substrate

low substrate conc, adding of substrate increase rate
high   ll                            ll                   little increase of rate coz reach maximum rate

increase temperature in crease rate
pH affect both ionic state and conformation

Km= michaelis constant - conct of substrate that produce half-maximal velocity
when conct Substrate very much less than Km, initial velocity depon in subs conct
   ll                                             greater ll                 ll                    is maximal
   ll                             equal to  Km                            ll                      half maxima

enzyme inhibitors

substrate analog , product of reaction, alternative substrate, substrate at high conct

competitive:  inhibition at active site V max unchanged, but Km increased
non competitive: inhibition at site other than active site , Km unchanges but Vmax decreased
irreversible: poisons eg heavy metal Hg2+  increase in sub conc do not relieve this inhibition

mixed inhibitor: inhibitor bind to enzyme and ES

BI-BI reaction = 2 substrate + 2 products
cleland nomenclature
ordered bi-bi sequential ordered : substrate A, then B , A induces conformation change that aligns residues essential for binding B
ping pong BI-BI : substrate , then product release , then substrate then second product released.

methanol bind to ethanol dehydrogenase, produce formaldehyde cause harmful effect, thus by increase conct of ethnaol, more ethanol will compete wif methanol and bind to enyzme ,thus reverse the effect of poisoning.

AG-1284 inhibitor for HIV protease , thus inhibit producing of new cell

insoluble in water
soluble in  non polar solvent

simple = fats`and waxes
complex = phospholipid and glycolipid
precursor and derived lipids

source of energy
storage energy in adipose tissue
thermal n electical insulator
cellular constituent in cell membrane

fatty acid   saturated anoid, no double bond, zigzag
                unsaturated , enoic , double bond , u shape

has carboxyl hydrophilic
non polar tail hydrphobic , thus it is amphiphilic

lauric acid = coconut
palmitic acid = palm oil
stearic acid = animal fats
oleic acid = olive oils
arachidonic acid = liver fats

Triacylglycerols
ester of alcohol gylcerol with 3 fatty acids by ester bonding, can break down by lipases
main storage form of fatty acids
storage form of energy
hydrophobic
neutral fat

phospholipid    glycerol + phosphate ( hydrophilic head)+ fatty acid( hydrophobic tail)

plasmanogen , similar to phospholipid except fatty acid group at carbon 1 of glycerol contain either an o-alkyl or 0-alkenyl ether
platelet activating factor

sphingolipids
composed of backbone sphingosine which derive itself from glycerol

4 classes of glycosphingolipids
cerebrosides
sulfarides
globosides
gangliosides

functions of phospholipids
main lipid constituent of cell membrane
cardiolipin is major lipid of mitochondrial membranes
phosphotidylinositol is precurosr of second messenger
lysophospholipid = intermediate in metabolism of phosphoglycerol
plasmologens = 10% of phospholipid of brain and muscle
sphingomyelins = brain and nerve tissue
glycolipid = nerve tissue and cell membrane

STEROIDS

Bile acid
Adrenocortical hormone
sex hormone
D vitamins
cardiac glycosides
sitosteroids
alkoloids

(CH20 ) n

alpha anomer, at 1st carbon, OH facing down
beta anomer , at 1st carbon, OH upward

ketose= C=0
aldose CH=O

stable ring of monosaccharide, 5 ring is furanose, 6 is pyranose

D  OH group on the right
L  OH group on the left

Monosaccharide : simplest sugar
colourless, soluble in h20, crystalline solid,
eg , 5 c = pentose: ribose, xylose, ribulose,xylulose
      6c = hexose : glucose, galactose, fructose

Disaccharide : water soluble, sweet tasting, crystalline solid, yield 2 monosaccharide via hydrolysis, glycosidic bond 1.4

sucrose = glucose + fructose cane sugar
lactose = glucose + galactose  milk sugar
maltose = glucose + glucose

OLIGOSACCHARIDE : POLYMER contain a small no of component of sugar. component of glycoproten or glycolipid. eg raffinose, maltodextrins, cellodextrins

Polysaccharide : polymers made up of many monosaccharide, insoluble in h20 no sweet tasting. large ,  branched or linear

energy storage and structural material.
starch: amylose + amylopectin, food and enery storahe
glycogen: highly branced , storage in liver n muscle
cellulose: structural component of cell wall, insoluble
inulin: polymer of  fructose as food storage
chitin: important structural of invertebrate

Reducing sugar: sugar with ketone or aldehyde group
sucrose not coz no aldehyde group available for bonding .
consist glucose and fructose joined by glycosidic bond   

it is an alcohol, any organic co factor which is
essential to body’s normal biochemistry as carriers and chemical reactants.

2 group fat souble (  A
, D , E ,K )

Water soluble ( B1,B2,B3,B5,B6,B12    ,  C )

in conjugation with enzymes as carriers of functional group in synthesis of
new molecule. several Vit B are cofactor for certain enzymes

as component of electron and proton carrier molecules in coupling of chemical
oxidation to phosphorylaton and synthesis of energy ATP.  niacin and
riboflavin.

as chemical reactants . ascorbic acid, vit E  and
beta carotene strong chemical reactants act as anti oxidant.

oxidation of ascorbic acid ( vit c )

reduction of proline to hydroxyproline

reduction of dopamine to NA

maintenance of lymphocyte function

VITAMIN C  = ascorbic
acid

water soluble natural antioxidant

defiecinecy cause survy = loose teeth and bleeding gum

wound repairing is slow if lack vitamin C

VITMAIN B1 = thiamine

decarboxylation = loss of CO2, intermediate formed is acetyl-CoA

disorders- beri-beri :
polyneuropathy,sensory loss, muscle wasting, eshaustion and cardial failure. 
lead to incomplete glucose utilisation, impaired synthesis of myelin. chronis
alcoholic , may hav dry beri-beri because consume little food .

VITAMIN B2 = riboflavin

riboflavin is the basic of flavine adenine dinucleotide and flavine adenine
mononucleotide . important in oxidation/reduction of krebs cycle.

deficiency: angular stomatitic, glossitis, ocular symptoms

VITAMIN B3 : NIACIN

nicotinic acid, deficiency is pellagra, symptoms
are diarrhoea, dermatitis, dementia.

VITAMIN B5 :
pantothenic acid

synthesis of coenzmye A

no clinically deficiency syndrome in man.

VITMAIN B12 = cobalamin
and cyanocobalamin

intrinsic factor

deficiency cause pernicious anemia, a form of megaloblastic anaemia, cause by
reduced secretion of intrinsic factor

VITAMIN B6 =
pyridoxine, pyridoxal phosphate

amino acid metabolism, decarboxylation, synthesis NA

overdose cause sensory neuropathy, should not exceed 200mg

FOLATE - folic acid

nucleic acid synthesis

deficiency cause megaloblastic anaemia

VITAMIN  H - biotin

uncooked egg white, contain avidin bind to biotin cause deficiency.

LIPID SOLUBLE VITAMIN = A E D K

VITAMIN A

retinol and beta carotene, latter is provitamin of retinol.vit A bind to
opsin, product is rhodopsin, activated when has cis orientation.

deficiency = night blindness, xerophthalmia, keratomalacia

overdose : increase intracarnial pressure, neurological symptoms, liver
toxicity

VITAMIN D -
calciferol

require action of UVlight, increase intestinal uptake of calcium and
phosphate  elimination by kidney.

deficiency : rickets in child and osteomalacia in adults

toxicity: mental retardation in child

VITAMIN E :
tocopherol

antioxidant prevent oxidation of cholesterol hence prevent formation of
plaque

VITAMIN K

formed in gut by intestinal bacteria

formation of blood clotting factos by liver

deficiency may cause by lack of intestinal flora, prolonged antibiotc
therapy, fat malasorption

Nucleic acid formed by nucleotides which consist of phosphate head, sugar and bases which could be purine or pyrimidine( single ring)

nucleotides are termed ribonucleotides if sugar is ribose sugar or deoxyribonucleotide if sugar is deoxy ribose.

nucleotides are phosporylated nucleosides

DNA      A G C T                        A G  = PURINE = double ring

mRNA   U C G A                        C T U = PYRIMIDINES = single ring

tRNA    A G C U

DNA : double helix/ stranded

very stable due to hydrogen bond

located in cell nucleus and packed into 46 chromosome

has repair mechanism

A T G C = bases    A-T    G-C   link via hydrogen bond

monomes unit held by phosphodiesterase bridge

RNA : single stranded

no repair mechanism

A G C U

mRNA , tRNA, rRNA, snRNA

DNA replication

duplication of DNA give rise to a new DNA molecule with the same base sequence as the original. consist of template strand and coding strand.

it is semi conservative

origin of replication start where DNA unwind breaking of H-bond.

RNA transcription occur in nucleus, where base sequence of DNA is reflected in the base sequence of RNA.

3 modification : capping by adding special nucleotide at 5 end of mRNA

add poly A tail to 3 end of mRNA

removal of non coding intron from mRNA by splicosome

then mRNA leave cytoplasm via nuclear pore to cytoplasm for translation

where base sequence of mRNA is translate into amino acid sequence of the corresponding specific protein.

ribosome is the translation center

tRNA help to translate mRNA info into specific sequence chain of amino acids in the ribosome.

Protein synthesis 3 steps

initiation : dissociation of ribosome into 40s and 60s subunit

elongation: elongation factor 1 alpha is required for binding of aminoacyl tRNA to A site. peptidyl transferase catalyses the formation of new peptide bond in protein synthesis.

elongation factor 2 needed for translocation in which mRNA moves with respect to ribosome, expose codon for next amino acid.

MUTATION: change in the nucleotide sequence of a gene

point mutation : change in a single gene

transition : purine to purine       A TO G

transversion : purine to pyrimidine   T TO G

deletion , insertion

splice site mutation

ATGCA GGGCAC TAGTA

AUGCA UAGUA

deletion of an exon

ATGCA GGGCAC TAGTA

AUGCA UAGUA

Insertion of nucleotide

ATGCA  =  ATGACA = AUGACA

deletion of a nucleotide

ATGCA = ATCA = AUCA

missense mutation

GGGCAC = GAGCAC

NEUTRAl polymorphism: alter in necleotide yet do not result in a change in encoded amino acid.

cytochrome P450 enzymes: responsible for metabolism of many drugs and chemicals. CYP2D6 amongs highest in liver metabolise 20 % drugs

CYP2D6 = significance

ultra-extensive metabolizer: rapid drug clearance

poor metabolizers : delayed drug clearance