AMINO ACID

BIOSYNTHESIS

NON-ESSENTIAL AMINO ACIDS

ESSENTIAL AMINO ACIDS
SINGLE CARBON TRANSFERS WITH THF
PHYSIOLOGIC AMINES

AMINO ACID BIOSYNTHESIS

FIXING OF ATMOSPHERIC N2

DIAZOTROPHS FIX N2 TO NH3

IN MICRO-ORGANISMS, PLANTS,
LOWER ANIMALS:
GLU

GLU + NAD(P)+ + H2O -KG + NH3 +

NAD(P)H + H+
REVERSE RXN GLU

GLU

DEHYDROGENASE RXN

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

ESSENTIAL AMINO ACIDS
*ARGININE
METHIONINE
HISTIDINE
PHENYLALANINE
ISOLEUCINE
THREONINE
LEUCINE
TRYPTOPHAN
LYSINE
VALINE
NOTE

ARG IS ESSENTIAL IN INFANTS AND CHILDREN

MOST SYNTHESIZED ARG ORNITHINE AND
UREA VIA THE UREA CYCLE

AMINO ACID BIOSYNTHESIS

NONESSENTIAL AMINO ACIDS

ALANINE
ASPARAGINE
ASPARTATE
*CYSTEINE
GLUTAMATE

GLUTAMINE
GLYCINE
PROLINE
SERINE
*TYROSINE

NOTE:
CYS GETS ITS SULFUR ATOM FROM MET
TYR IS HYDROXYLATED PHE
SO ITS 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 ISNT AN OPTION

BUT THEY ARE PRESENT IN COMMON PATHWAYS

OF MICRO-ORGANISMS AND PLANTS

AMINO ACID BIOSYNTHESIS OVERVIEW

(USE OF COMMON INTERMEDIATES)
GLUCOSE GLUC-6-PHOSPHATE RIB-5-PHOS HIS

3-PHOSPHOGLYCERATE

SERINE

GLYCINE
E-4-PHOS +
PEP
CYSTEINE

PHETYR
PYRUVATE

ALA
TRP

VAL
CITRATE
LEU, ILE

OXALOACETATE, -KETOGLUTARATE
ASP, ASN, GLU, GLN, PRO, ARG, LYS, THR, MET

SYNTHESIS OF NON-ESSENTIAL
AMINO ACIDS
ALL (EXCEPT TYR) SYNTHESIZED

FROM COMMON INTERMEDIATES

SYNTHESIZED IN CELL

PYRUVATE
OXALOACETATE
-KETOGLUTARATE
3-PHOSPHOGLYCERATE

SYNTHESIS OF NON-ESSENTIAL
AMINO ACIDS
TRANSAMINATION REACTIONS: ONE STEP

PYRUVATE + AA ALANINE + -KETOACID

OXALOACETATE + AA ASPARTATE + KETOACID
-KETOGLUTARATE + AA GLUTAMATE + KETOACID

TRANSAMINASES: EQUILIBRATE AMINO GROUPS

REQUIRE PYRIDOXAL PHOSPHATE (PLP)

ALL AAs, EXCEPT LYS, CAN BE TRANSAMINATED
MOST TRANSAMINASES GENERATE GLU OR ASP

WHY?

LOOK AT MECHANISM OF PLP (PAGE 987 IN TEXT)

SYNTHESIS OF NONESSENTIAL
AMINO ACIDS
ATP-DEPENDENT AMIDATION OF ASP, GLU
ASN, GLN
GLU + ATP + NH GLN + ADP + P
3
i
GLUTAMINE SYNTHETASE
NH IS TOXIC; ITS STORED AS GLN
3

GLN DONATES AMINO GPS IN MANY

REACTIONS

ASP + ATP + GLN ASN + AMP + PPi +

GLU
ASPARAGINE SYNTHETASE

SYNTHESIS OF NONESSENTIAL
AMINO ACIDS
NITROGEN METABOLISM IS CONTROLLED BY

REGULATION OF GLUTAMINE SYNTHETASE

IN MAMMALS, GLN SYNTHETASES ACTIVATED

BY -KG
EXCESS AAs TRANSAMINATED TO GLU
OXIDATIVE DEAMINATION OF GLU -KG
+ NH3
NH
3 UREA OR GLN (STORAGE)

-KG IS A SIGNAL THAT ACTIVATES GLN

SYNTHETASE

BACTERIAL GLUTAMINE
SYNTHETASE
VERY DETAILED CONTROL SYSTEM
12 IDENTICAL SUBUNITS (HEX PRISM)

ALLOSTERIC CONTROL
9 FEEDBACK INHIBITORS (CUMULATIVE INH)
INDIVIDUAL BINDING SITES
6 ARE END-PRODS OF PATHWAYS FROM GLN
HIS, TRP, CARBAMOYL PHOSPHATE, AMP,
CTP, GLUCOSAMINE-6-PHOSPHATE
3 REFLECT CELLS N LEVEL (ALA, SER, GLY)

ALSO COVALENTLY MODIFIED BY

ADENYLYLATION

BACTERIAL GLUTAMINE
SYNTHETASE
BRIEF REVIEW: REGULATING ENZYME

ACTIVITY

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

CONTROL OF ENZYME ACTIVITY

ALLOSTERIC REGULATION
COVALENT MODIFICATION
GENETIC CONTROL

AT LEVEL OF TRANSCRIPTION

BACTERIAL GLUTAMINE
SYNTHETASE
SEE REGULATORY DIAGRAM (PAGE 1035)
ADENYLYLATION OF A SPECIFIC TYR
RESIDUE
LESS ACTIVITY OF THE ENZYME
ENZYME IS ADENYLYLTRANSFERASE IN A
COMPLEX WITH A TETRAMERIC
REGULATORY PROTEIN, PII
URIDYLYLATION OF P (AT A TYR)
II
DEADENYLYLATION
A URIDYL-REMOVING ENZYME RESULTS IN
ADENYLYLTRANSFERASE CATALYZING
ADENYLYLATION OF GLN SYNTHETASE

BACTERIAL GLUTAMINE
SYNTHETASE
SEE REGULATORY DIAGRAM (PAGE 1035)

WHAT CONTROLS ACTIVITY OF URIDYLYL

TRANSFERASE?
ACTIVATED BY -KG AND ATP
DEACTIVATED BY GLN AND P
i

URIDYL-REMOVING ENZYME INSENSITIVE

TO THESE

BACTERIAL GLUTAMINE
SYNTHETASE
IN-CLASS EXERCISE

EXPLAIN THE SIGNIFICANCE OF -KG AS AN

ACTIVATOR OF GLUTAMINE SYNTHETASE
SHOW, IN DETAIL, THE EFFECT OF LEVEL
OF -KG ON THIS ENZYME.
DO THE SAME FOR ATP, GLN AND Pi

NONESSENTIAL AMINO ACID

SYNTHESIS
PRO, ORNITHINE, ARG ARE DERIVED FROM GLUTAMATE

NOTE: 7 OF THE 10 NONESSENTIALS ARE ULTIMATELY

DERIVED FROM PYR, -KG AND OXALOACETATE

SEE PATHWAYS ON PAGE 1036

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

SER (A 3-STEP PATHWAY)

(1) 3-PG + NAD+ 3-PHOSPHOHYDROXYPYRUVATE + NADH + H+
(2) 3-PHP + GLU 3-PHOSPHOSERINE + -KG
(3) 3-PHOSPHOSERINE + H2O SER + Pi

GLY (2 DIFFERENT WAYS)

(1) SER + THF GLY + N5,N10 METHYLENE-THF (DIRECT)
(2) N5,N10 METHYLENE-THF + CO2 + NH4+ GLY + THF
(CONDENSATION)

NONESSENTIAL AMINO ACID

SYNTHESIS
CYSTEINE

SER + HOMOCYSTEINE
CYSTATHIONINE
HOMOCYSTEINE

IS 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:

ALL NONESSENTIALS (EXCEPT TYR) ARE

DERIVED FROM ONE OF THE
FOLLOWING COMMON INTERMEDIATES:
PYRUVATE
OXALOACETATE
-KG

3-PHOSPHOGLYCERATE

IN-CLASS EXERCISE

WHICH OF THE 4 AMINO ACID INTERMEDIATES OF THE

UREA CYCLE IS ESSENTIAL IN CHILDREN?

OUTLINE A PATHWAY BY WHICH ADULTS CAN

SYNTHESIZE THIS AA FROM 1 GLUCOSE MOLECULE.

HINTS: YOU WILL NEED TO CONSIDER THE
FOLLOWING METABOLIC PATHWAYS:
GLYCOLYTIC
GLUCONEOGENIC
CITRIC ACID CYCLE
GLUTAMATE DEHYDROGENASE REACTION

ASSUME IT CAN GO IN REVERSE DIRECTION

ORNITHINE PRODUCTION
UREA CYCLE

TRANSFER OF C1 UNITS TO
METABOLIC PRECURSORS
MOST CARBOXYLATION REACTIONS USE A

BIOTIN COFACTOR

EXAMPLE: PYRUVATE CARBOXYLASE

REACTION

S-ADENOSYLMETHIONINE (SAM) AS A

METHYLATING AGENT

CYTOSINE METHYLATION OF CpGs IN GENE

PROMOTER REGIONS

TETRAHYDROFOLATES
CAN TRANSFER SINGLE C UNITS IN A NUMBER
OF DIFFERENT OXIDATION STATES

TETRAHYDROFOLATES
REVIEW STRUCTURE (PAGE 1028 OF TEXT)
FOCUS ON HETEROCYCLIC RING STRUCTURE
2-AMINO-4-OXO-6-METHYLPTERIN
NOTICE THE NUMBERING OF THE ATOMS
LOOK AT N5
PABA JOINS TO 2-AMINO-4-OXO-6METHYLPTERIN TO FORM PTEROIC ACID
FIND N10
COVALENT ATTACHMENT OF C1 UNITS AT
N5
N10
BOTH

TETRAHYDROFOLATE
THREE DIFFERENT OXIDATION STATES

METHANOL

METHYL (-CH3)

FORMALDEHYDE

AT N5
AT N5,N10

METHYLENE (-CH2-)

FORMATE

FORMYL (-CH=O)
FORMIMINO (-CH=NH)
METHENYL ( -CH=)

AT N5 OR N10
AT N5
AT N5,N10

LOOK AGAIN AT THE 2 REACTIONS FOR SYNTHESIS OF

GLY

SERINE HYDROXYMETHYLTRANSFERASE
GLYCINE SYNTHASE

THF IS INVOLVED IN EACH

TETRAHYDROFOLATE
C1 UNITS ENTER THE THF POOL MAINLY

FROM THESE TWO REACTIONS

AS N5,N10 METHYLENE-THF

OXIDATION STATES OF C1 UNITS ATTACHED

TO THF ARE INTERCONVERTIBLE
VIA ENZYMATIC REDOX REACTIONS

WE WILL SEE THF AGAIN

METHIONINE SYNTHESIS
HIS SYNTHESIS
PURINE SYNTHESIS
dTMP (THYMIDYLATE) SYNTHESIS

TETRAHYDROFOLATE
THF IS DERIVED FROM FOLIC ACID
MAMMALS CANNOT SYNTHESIZE IT
DEFICIENCY DURING EARLY PREGNANCY CAN
LEAD TO NEURAL TUBE DEFECTS
ANENCEPHALY
SPINA BIFIDA
BACTERIA SYNTHESIZE FOLIC ACID

SULFONAMIDES COMPETITIVELY INHIBIT

STRUCTURAL ANALOGS OF PABA
GOOD ANTIBACTERIAL AGENTS
WHY ARE MAMMALS UNAFFECTED?

TETRAHYDROFOLATE
STUDY QUESTION: IF I GIVE YOU THE

STRUCTURE OF THF, NUMBERING THE

ATOMS ACCORDINGLY, BE ABLE TO SHOW
WHERE TO ATTACH THE 5 DIFFERENT C1
GROUPS.

TRANSAMINATION REACTIONS
IN-CLASS STUDY QUESTION
DRAW THE STRUCTURES OF THE KETO-

ACID PRODUCTS OF THE REACTIONS OF

THE FOLLOWING AMINO ACIDS WITH -KG.

GLY
ARG
SER

DRAW THE STRUCTURE OF THE AMINO

ACID PRODUCT COMMON TO ALL 3 RXNS

REFERENCES
HERE ARE TWO ARTICLES THAT MIGHT

HELP YOU TO ORGANIZE YOUR THINKING

ABOUT AMINO ACID METABOLISM:
(1) Glutamate and Glutamine, at the Interface between Amino Acid and
Carbohydrate Metabolism
(Brosnan JT, The Journal of Nutrition, Apr 2000, 130,4S: 988S 990S)
(2) Disorders of Glutamate Metabolism
(Kelly A, Stanley CA, 2001. Mental Retardation and Developmental
Disabilities Research Reviews, 7:287-295

SYNTHESIS OF ESSENTIAL AMINO

ACIDS
ALL SYNTHESIZED FROM COMMON METABOLIC

PRECURSORS

ASPARTATE
PYRUVATE
PHOSPHOENOLPYRUVATE
ERYTHROSE-4-PHOSPHATE
PURINE + ATP (HISTIDINE)

PATHWAYS ONLY IN MICRO-ORGANISMS AND

PLANTS

PROBABLE EVOLUTIONARY LOSS IN MAMMALS

PATHWAYS ARE VERY COMPLICATED
ACTUAL PATHWAYS VARY ACROSS SPECIES!

IN CONTRAST TO LIPID AND CARBOHYDRATE

PATHWAYS, WHICH ARE ALMOST UNIVERSAL

ESSENTIAL AMINO ACID SYNTHESIS

FOUR FAMILIES
ASPARTATE
LYS
MET
THR
PYRUVATE
LEU, ILE, VAL (THE BRANCHED CHAIN
AMINO ACIDS)
AROMATIC
PHE
TYR
TRP
HISTIDINE

THE ASPARTATE FAMILY

FIRST COMMITTED STEP IS

ASP + ATP ASPARTYL-PHOSPHATE + ADP

ENZYME:

ASPARTOKINASE

3 ISOZYMES IN E.coli
EACH RESPONDS DIFFERENTLY AS FAR
AS FEEDBACK INHIBITION AND
REPRESSION OF ENZYME SYNTHESIS

THR,LYS,

MET PATHWAYS
INDEPENDENTLY CONTROLLED

THE ASPARTATE FAMILY

CONTROL OF ASPARTOKINASE
ISOENZYMES

ENZYME

FEEDBACK INHIB COREPRESSOR

ASP I
ASP II
ASP III

THR
NONE
LYS

THR, ILE
MET
LYS

COREPRESSOR: TRANSCRIPTIONAL REPRESSION

ASPARTATE FAMILY
ALSO CONTROL AT BRANCH POINTS
NOTE THE FOLLOWING REACTION:

HOMOCYSTEINE + N5-METHYL-THF MET + THF

ENZYME: METHIONINE SYNTHASE (?)

HOMOCYSTEINE CV DISEASE RISK FACTOR

EAT FOODS CONTAINING FOLATE
RECALL:SER + HOMOCYSTEINE CYSTATHIONINE
ENZYME DEFECTS IN REMETHYLATION OF HOMOCYSTEINE TO
MET OR IN RXN FROM CYSTATHIONINE CYS
HOMOCYSTEINE
DEFECT IN SYNTHESIS OF CYSTATHIONE--SYNTHASE

HYPER HOMOCYSTENEMIA HOMOCYSTEINURIA

SYMPTOMS:

PREMATURE ATHEROSCLEROSIS
THROMBOEMBOLIC COMPLICATIONS
SKELETAL ABNORMALITIES
ECTOPIA LENTIS
MENTAL RETARDATION

THE PYRUVATE FAMILY

BRANCHED CHAIN AMINO ACIDS
LEU
ILE
VAL
VAL, ILE: SAME PATHWAY AFTER 1st STEP
LEU PATHWAY BRANCHES FROM VAL

PATHWAY
FINAL STEPS ALL CATALYZED BY AMINOTRANSFERASES

GLU IS THE AMINO DONOR

THE PYRUVATE FAMILY

THE FIRST STEP:

PYR + TPP HYDROXYETHYL-TPP

FIRST

PYR AND TPP FORM AN ADDUCT

THEN DECARBOXYLATED TO HE-TPP
A RESONANCE-STABILIZED CARBANION

A STRONG NUCLEOPHILE
ADDS TO KETO GROUP OF
PYRUVATE VAL, LEU
-KETOBUTYRATE ILE

THE PYRUVATE FAMILY

LOOK AT THE REACTION MECHANISM OF PYRUVATE

DECARBOXYLASE (PAGE 605)

THIS SHOWS THE FORMATION OF THE

HYDROXYETHYL-TPP ADDUCT
THIAMINE (VIT B1)

SOME INTERESTING CHEMISTRY

THIAZOLIUM RING

ACIDIC HYDROGEN
ELECTRON SINK

TRANSITION STATE STABILIZATION MECH.

YLIDS
RESONANCE

THE AROMATIC FAMILY

IN PLANTS AND MICRORGANISMS

PHE
TYR
TRP

PECURSORS ARE:

PEP
ERYTHROSE-4-PHOSPHATE
THESE CONDENSE WITH ULTIMATE
CONVERSION TO CHORISMATE

THE AROMATIC FAMILY

CHORISMATE
BRANCH POINT FOR TRP SYNTHESIS
CHORISMATE ANTHRANILATE TRP
CHORISMATE PREPHENATE
PREPHENATE

BRANCH POINT FOR PHE, TYR SYNTH

AMINOTRANSFERASES IN EACH FINAL STEP

IN MAMMALS, TYR IS A PRODUCT OF:

PHE HYDROXYLATION

THE TRP PATHWAY

TRYPTOPHAN SYNTHASE

CATALYZES FINAL 2 STEPS

INDOLE-3-GLYCEROL PHOS INDOLE + GLYC-3-P

INDOLE + SER H2O + TRP

22 BIFUNCTIONAL ENZYME

WHAT ENZYME CLASS?

THE TRP PATHWAY

CHANNELING
INDOLE IS SEQUESTERED BETWEEN THE
TWO ACTIVE SITES
DIFFUSES BETWEEN TWO SITES
ITS NONPOLAR
STUDY QUESTION:

WHAT ARE THE BENEFITS OF CHANNELING?

SEE RIBBON DIAGRAM OF TRP SYNTHASE

ON PAGE 1044

MECHANISM?

PHENYLKETONURIA (PKU)

DEFECTIVE OR ABSENT PHENYLALANINE

HYDROXYLASE
CANNOT FORM TYROSINE
PHE BUILDS UP
PHE IS TRANSAMINATED TO PHENYL-PYRUVATE
SEVERE MR IF NOT TREATED SOON AFTER BIRTH
WITH LOW PHE DIET
UNIVERSAL NEWBORN SCREENING

PHENYLKETONURIA
IN-CLASS STUDY QUESTION
WRITE OUT THE REACTION IN WHICH PHE IS

TRANSAMINATED TO PHENYLPYRUVATE, SHOWING

STRUCTURES
EXPLAIN WHY CHILDREN WITH A TETRAHYDROBIOPTERIN DEFICIENCY EXCRETE LARGE
AMOUNTS OF PHE
WHY DO PEOPLE WITH PKU HAVE BLOND HAIR,
BLUE EYES AND VERY LIGHT SKIN?
WHY DO PEOPLE ON A LOW PHE-DIET NEED TO
INCREASE THEIR TYR INTAKE?

HISTIDINE BIOSYNTHESIS
ATOMS DERIVED FROM:

5-PHOSPHORIBOSYL--PYROPHOSPHATE
PROVIDES 5 C-ATOMS
PRPP INVOLVED IN PURINE SYNTHESIS
PRPP INVOLVED IN PYRIMIDINE SYNTHESIS
PURINE SALVAGE PATHWAY
AN INTERMEDIATE IN TRP SYNTHESIS

ATP PROVIDES THE 6th C-ATOM

ATP + -D-RIBOSE-5-PHOSPHATE PRPP +

AMP

-D-RIBOSE-5-PHOSPHATE FROM H-M SHUNT

HISTIDINE BIOSYNTHESIS
NOTICE THE PRODUCTS OF THE AMIDO-

TRANSFERASE STEP:

AICAR
AN INTERMEDIATE IN PURINE BIOSYNTHESIS
IMIDAZOLE GLYCEROL PHOSPHATE

THERE IS AN APPARENT EVOLUTIONARY

OVERLAP OF PURINE AND HIS SYNTHESIS

THE FIRST STEP IN HIS SYNTHESIS INVOLVES

FORMATION OF A PURINE!

HISTIDINE BIOSYNTHESIS
IS THE HIS PATHWAY A RELIC OF THE

TRANSITION FROM RNA-BASED TO

PROTEIN-BASED LIFE FORMS?

HIS IS FREQUENTLY FOUND IN

ENZYME ACTIVE SITES

NUCLEOPHILES
GENERAL ACID/BASE CATALYSIS

RNA HAS CATALYTIC PROPERTIES

IMIDAZOLE GROUP PROBABLY PLAYS A
SIMILAR ROLE

PHYSIOLOGICALLY ACTIVE
AMINES
THESE ARE DERIVED FROM AMINO ACIDS
THEY INCLUDE

EPINEPHRINE (ADRENALINE)
NOREPINEPHRINE
DOPAMINE
SEROTONIN
-AMINOBUTYRIC ACID (GABA)

HORMONES
NEUROTRANSMITTERS

PHYSIOLOGICALLY ACTIVE
AMINES
DECARBOXYLATION OF PRECURSOR

AMINO ACID

PLP-DEPENDENT, AA DECARBOXYLASES

TYR DOPAMINE, EPI, NOREPINEPHRINE

GLUTAMATE GABA
HISTIDINE HISTAMINE
TRP SEROTONIN

DECARBOXYLATION REACTION
PLP FORMS A SCHIFF BASE WITH AA
RESULTS IN FORMATION OF C CARBANION

UNSTABLE CHARGE BUILDUP ON C WHEN

CO2 SPLITS OFF

PLP IS AN ELECTRON SINK

IN-CLASS EXERCISE: USING THE STRUCTURE OF

THE AMINO-ACID-PLP SCHIFF BASE AS SHOWN IN

CLASS, SHOW (USING ARROWS TO SHOW FLOW OF
ELECTRONS) HOW THE C CARBANION FORMED
AFTER CO2 SPLITS OFF IS STABILIZED.

GABA
GLUTAMATE GABA + CO2

GLU DECARBOXYLASE

GABA IS THE MAJOR INHIBITORY NEURO-

TRANSMITTER IN BRAIN

GLU IS THE MAJOR EXCITATORY NEUROTRANSMITTER

STIMULATION OF NEURONS BY GABA

PERMEABILITY TO CHLORIDE IONS

BENZODIAZEPINES (VALIUM) ENHANCE

MEMBRANE PERMEABILITY OF Cl IONS BY GABA
GABAPENTIN PROTECTS AGAINST GLU
EXCITOTOXICITY

HISTAMINE
HISTIDINE HISTAMINE + CO2

HIS DECARBOXYLASE

HISTAMINES INVOLVED IN

ALLERGIC RESPONSE
H

RECEPTORS IN GUT, BRONCHI

STIMULATION SMOOTH MUSCLE
CONTRN
H1 RECEPTOR ANTAGONISTS

CLARITIN, ZYRTEC, ETC

HISTAMINE
HISTAMINES INVOLVED IN
CONTROL OF ACID SECRETION IN STOMACH
H RECEPTORS
2
STIMULATION HCl SECRETION
H ANTAGONISTS
2
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
EPI, NOREPINEPHRINE, DOPAMINE
AMINE DERIVATIVES OF CATECHOL
REACTIONS:

TYR L- DOPA

L-DOPA DOPAMINE + CO2

AROMATIC ACID DECARBOXYLASE

DOPAMINE NOREPINEPHRINE

TYR HYDROXYLASE

DOPAMINE -HYDROXYLASE

NOREPINEPHRINE EPINEPHRINE

REQUIRES SAM

L-DOPA AND DOPAMINE

IN SUBSTANTIA NIGRA, CATECHOLAMINE

PRODUCTION STOPS AT DOPAMINE

PARKINSONS DISEASE: DEGENERATION OF

SUBSTANTIA NIGRA DOPAMINE
TREAT BY GIVING PRECURSOR, L-DOPA
DOPAMINE CANNOT CROSS BLOOD/BRAIN
BARRIER
TRANSPLANTATION OF ADR. MEDULLA CELLS
TO BRAIN

L-DOPA A PRECURSOR OF MELANIN

PRODUCTION

IN-CLASS EXERCISE
IN KWASHIORKOR, A DIETARY PROTEIN

DEFICIENCY DISEASE IN CHILDREN,

DEPIGMENTATION OF HAIR AND SKIN IS
SEEN.
EXPLAIN THE BIOCHEMICAL BASIS FOR
THIS.

S-ADENOSYLMETHIONINE

ACTIONS OF NOREPINEPHRINE
NOT NEARLY AS ACTIVE AS EPINEPHRINE
DURING EXTREME STRESS
CIRCULATORY SYSTEM
CONSTRICTS GREAT VEINS ( )
2
VASOCONSTRICTIVE TO SKIN ( )
1
VASOCONSTRICTION ( ) EFFECTS ON
1
GI TRACT
SPLEEN
PANCREAS
KIDNEYS
NEUROTRANSMITTER IN THE BRAIN

ACTIONS OF EPINEPHRINE
AS AN INSULIN ANTAGONIST

ACTIVATES MUSCLE GLYCOGEN

PHOSPHORYLASE

TRIGGERS PHOSPHORYLATION (ACTIVATION) OF

HORMONE-SENSITIVE LIPASE IN FAT CELLS

GLUCOSE-6-P USED IN GLYCOLYSIS

MOBILIZES FAT BY HYDROLYZING TGs

GLYCOGEN BREAKDOWN IN LIVER

ACTIVATES GLUCONEOGENESIS IN LIVER
INHIBITS FATTY ACID SYNTHESIS

ACTIONS OF EPINEPHRINE
ON CARDIAC MUSCLE
-ADRENERGIC RECEPTOR STIMULATION
1
HEART RATE AND CARDIAC OUTPUT

-BLOCKERS BLOOD PRESSURE

DILATES CORONARY ARTERIES (2)

ON SMOOTH MUSCLE (2-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

EXPLAIN WHY IT IS POSSIBLE FOR THE

CARBON SKELETON OF EACH AMINO ACID

TO BE BROKEN DOWN TO ACETYL-CoA.

AMINO ACID DEGRADATION INTERMEDIATES

Glucogenic

Ile*
Leu
Lys
Thr*

Ala Ser
Cys Thr*
Gly Trp*

Ketogenic

* Both Glucogenic and Ketogenic

Purely Ketogenic

CO2

Glucose

Pyruvate
Acetyl-CoA

Acetoacetate

Asn
Asp
Citrate

Oxaloacetate

Asp
Phe*
Tyr*

Fumarate

Leu Trp*
Lys Tyr*
Phe*

Citric
Acid
Cycle

Isocitrate
CO2

Ile*
Met
Val

Succinyl-CoA

-ketoglutarate
CO2

Arg His
Glu Pro
Gln