Beruflich Dokumente
Kultur Dokumente
BIOSYNTHESIS
“FIXING” OF ATMOSPHERIC N2
DIAZOTROPHS FIX N2 TO NH3
IN MICRO-ORGANISMS, PLANTS,
LOWER ANIMALS:
GLU DEHYDROGENASE RXN
GLU + NAD(P)+ + H2O -KG + NH3 +
NAD(P)H + H+
REVERSE RXN GLU
GLU SYNTHASE RXN’ GLU
NADPH + H+ + GLN + -KG 2 GLU +
NADP+
AMINO ACID BIOSYNTHESIS
DOES THE GLU DEHYDROGENASE RXN’ WORK IN
REVERSE IN MAMMALS?
THERE IS SOME CONTROVERSY ABOUT THIS
THE HYPERAMMONEMIA/HYPERINSULINEMIA SYNDROME
(HI/HA) IS CAUSED BY A MUTATION IN GDH THAT A GAIN IN
FUNCTION
SUGGESTS THAT THE PREFERRED DIRECTION IS TOWARD
THE RIGHT
DEPENDING UPON THE ORGANISM, THE GLU
DEHYDROGENASE MIGHT BE CLOSE TO EQUILIBRIUM, OR
FAVORED TO THE RIGHT OR LEFT
SO, PREFORMED -AMINO NITROGEN, IN THE FORM
OF GLU, MUST BE CONSIDERED AN ESSENTIAL
NUTRIENT
AMINO ACID BIOSYNTHESIS
ALANINE GLUTAMINE
ASPARAGINE GLYCINE
ASPARTATE PROLINE
*CYSTEINE SERINE
GLUTAMATE *TYROSINE
NOTE:
CYS GETS ITS SULFUR ATOM FROM MET
TYR IS HYDROXYLATED PHE
SO IT’S NOT REALLY NONESSENTIAL
AMINO ACID BIOSYNTHESIS
ALL ARE SYNTHESIZED FROM COMMON METABOLIC
INTERMEDIATES
NON-ESSENTIAL
TRANSAMINATION OF -KETOACIDS THAT ARE
AVAILABLE AS COMMON INTERMEDIATES
ESSENTIAL
THEIR -KETOACIDS ARE NOT COMMON
INTERMEDIATES (ENZYMES NEEDED TO FORM
THEM ARE LACKING)
SO TRANSAMINATION ISN’T AN OPTION
BUT THEY ARE PRESENT IN COMMON PATHWAYS
OF MICRO-ORGANISMS AND PLANTS
AMINO ACID BIOSYNTHESIS OVERVIEW
(USE OF COMMON INTERMEDIATES)
PYRUVATE
OXALOACETATE
-KETOGLUTARATE
3-PHOSPHOGLYCERATE
SYNTHESIS OF NON-ESSENTIAL
AMINO ACIDS
TRANSAMINATION REACTIONS: ONE STEP
B
SYNTHESIS OF NONESSENTIAL
AMINO ACIDS
+ NH3
NH3 UREA OR GLN (STORAGE)
NEAR-EQUILIBRIUM (REVERSIBLE)
REACTANTS, PRODUCTS ~ EQUIL. VALUES
ENZYMES ACT QUICKLY TO RESTORE EQUIL.
RATES REGULATED BY [REACT], [PROD]
FAR FROM EQUILIBRIUM (IRREVERSIBLE)
ENZYME SATURATED
NOT ENOUGH ACTIVITY TO ALLOW EQUIL.
RATE INSENSITIVE TO [REACT], [PROD]
“STEADY STATE” (CONSTANT FLUX)
“RATE-DETERMINING STEP”
BACTERIAL GLUTAMINE
SYNTHETASE
BRIEF REVIEW: REGULATING ENZYME
ACTIVITY
ALLOSTERIC REGULATION
COVALENT MODIFICATION
GENETIC CONTROL
AT LEVEL OF TRANSCRIPTION
BACTERIAL GLUTAMINE
SYNTHETASE
Synthetase O P O CH2
Adenine
O
Regulation O
H
H H
H
HO OH
Uridylyltransferase
-Ketoglutarate
ATP
Glutamine X Adenylyltransferase
PPi Pi X PII
Adenylyltransferase
UTP PPi Pi
PII
O
ATP
O P O CH2
Uracil ADP
OH UMP H2O O
H H
O
H H
HO OH
Uridylyl-removing Enzyme
Glutamine Synthetase
BACTERIAL GLUTAMINE
SYNTHETASE
IN-CLASS EXERCISE
HIGHLIGHTS:
STEP 1: ACTIVATE GLU; A KINASE
GLUTAMATE-5-SEMIALDEHYDE BRANCH POINT
SPONTANEOUS CYCLIZATION TO AN INTERNAL SCHIFF
BASE
PRO
TRANSAMINATION TO ORNITHINE ARG IN UREA CYCLE
SCHIFF BASE: AMINE + (ALDEHYDE OR KETONE)
IMINE (CONTAINS A C=N BOND)
NONESSENTIAL AMINO ACID
SYNTHESIS
3-PHOSPHOGLYCERATE IS PRECURSOR OF
CYSTEINE
SER + HOMOCYSTEINE
CYSTATHIONINE
HOMOCYSTEINEIS A BREAKDOWN
PRODUCT OF METHIONINE
CYSTATHIONINE -KETOBUTYRATE
+ CYS
NOTE: -SH GROUP COMES FROM MET
SO CYS IS ACTUALLY AN ESSENTIAL AMINO
ACID
NONESSENTIAL AMINO ACID
SYNTHESIS
SUMMARY POINT:
PYRUVATE
OXALOACETATE
-KG
3-PHOSPHOGLYCERATE
IN-CLASS EXERCISE
METHANOL AT N5
METHYL (-CH3)
FORMALDEHYDE AT N5,N10
METHYLENE (-CH2-)
FORMATE
FORMYL (-CH=O) AT N5 OR N10
FORMIMINO (-CH=NH) AT N5
METHENYL ( -CH=) AT N5,N10
LOOK AGAIN AT THE 2 REACTIONS FOR SYNTHESIS OF
GLY
SERINE HYDROXYMETHYLTRANSFERASE
GLYCINE SYNTHASE
THF IS INVOLVED IN EACH
TETRAHYDROFOLATE
FOUR “FAMILIES”
ASPARTATE
LYS
MET
THR
PYRUVATE
LEU, ILE, VAL (THE “BRANCHED CHAIN”
AMINO ACIDS)
AROMATIC
PHE
TYR
TRP
HISTIDINE
THE ASPARTATE FAMILY
CONTROL OF ASPARTOKINASE
ISOENZYMES
CHORISMATE
BRANCH POINT FOR TRP SYNTHESIS
CHORISMATE ANTHRANILATE TRP
CHORISMATE PREPHENATE
PREPHENATE
BRANCH POINT FOR PHE, TYR SYNTH
AMINOTRANSFERASES IN EACH FINAL STEP
TRYPTOPHAN SYNTHASE
CATALYZES FINAL 2 STEPS
“CHANNELING”
INDOLE IS SEQUESTERED BETWEEN THE
TWO ACTIVE SITES
DIFFUSES BETWEEN TWO SITES
IT’S NONPOLAR
STUDY QUESTION:
WHAT ARE THE BENEFITS OF CHANNELING?
SEE RIBBON DIAGRAM OF TRP SYNTHASE
ON PAGE 1044
MECHANISM?
PHENYLKETONURIA (PKU)
HISTAMINES INVOLVED IN
CONTROL OF ACID SECRETION IN STOMACH
H2 RECEPTORS
STIMULATION HCl SECRETION
H2 ANTAGONISTS
CIMETIDINE
RANITIDINE
H2 RECEPTORS IN HEART
STIMULATION HEART RATE
SEROTONIN
TRP 5-HYDROXYTRYPTOPHAN
TRP HYDROXYLASE
REQUIRES 5,6,7,8 TETRAHYDROBIOPTERIN
5-HT SEROTONIN + CO2
AROMATIC ACID DECARBOXYLASE
SEROTONIN CAUSES
SMOOTH MUSCLE CONTRACTION
BRAIN NEUROTRANSMITTER
MELATONIN SYNTHESIZED IN PINEAL GLAND
CATECHOLAMINES
REACTIONS:
TYR L- DOPA
TYR HYDROXYLASE
L-DOPA DOPAMINE + CO2
AROMATIC ACID DECARBOXYLASE
DOPAMINE NOREPINEPHRINE
DOPAMINE β-HYDROXYLASE
NOREPINEPHRINE EPINEPHRINE
REQUIRES SAM
L-DOPA AND DOPAMINE
CIRCULATORY SYSTEM
CONSTRICTS GREAT VEINS (2)
VASOCONSTRICTIVE TO SKIN (1)
VASOCONSTRICTION (1) EFFECTS ON
GI TRACT
SPLEEN
PANCREAS
KIDNEYS
AS AN INSULIN ANTAGONIST
ACTIVATES MUSCLE GLYCOGEN
PHOSPHORYLASE
GLUCOSE-6-P USED IN GLYCOLYSIS
TRIGGERS PHOSPHORYLATION (ACTIVATION) OF
HORMONE-SENSITIVE LIPASE IN FAT CELLS
MOBILIZES FAT BY HYDROLYZING TGs
GLYCOGEN BREAKDOWN IN LIVER
ACTIVATES GLUCONEOGENESIS IN LIVER
INHIBITS FATTY ACID SYNTHESIS
ACTIONS OF EPINEPHRINE
ON CARDIAC MUSCLE
β1 -ADRENERGIC RECEPTOR STIMULATION
HEART RATE AND CARDIAC OUTPUT
β-BLOCKERS BLOOD PRESSURE
DILATES CORONARY ARTERIES (β2)
ON SMOOTH MUSCLE (β2-ADRENERGIC)
IN BRONCHIOLES, FOR EXAMPLE
MUSCLE RELAXATION
ACTIVATION OF G-PROTEINS
cAMP , ETC
ASTHMA MEDICATIONS
AMINO ACID METABOLISM
SUMMARY 1
SYNTHESIS
ESSENTIAL
ASPARTATE FAMILY
PYRUVATE FAMILY
AROMATIC
HISTIDINE
NON-ESSENTIAL
PYRUVATE
OXALOACETATE
-KETOGLUTARATE
3-PHOSPHOGLYCERATE
AMINO ACID METABOLISM
SUMMARY 2
DEGRADATION TO:
PYRUVATE
ACETYL-CoA
ACETOACETATE
-KETOGLUTARATE
SUCCINYL-CoA
FUMARATE
OXALOACETATE
AMINO ACID METABOLISM
SUMMARY 3
KETOGENIC
LEU
LYS
GLUCOGENIC
ALL NON-ESSENTIALS + HIS, VAL,MET
BOTH
ILE
PHE
THR
TRP
TYR
IN-CLASS STUDY QUESTION
CO2
Pyruvate
Glucose
Acetyl-CoA Acetoacetate
Asn Leu• Trp*
Asp Lys• Tyr*
Citrate Phe*
Oxaloacetate
Asp Citric
Phe* Acid Isocitrate
Tyr* Fumarate Cycle
CO2