Amino Acids & disorders

Amino Acids

Protein Precipitation

Does not require titration with reducing sugar.

Can be done by:

Isoelectric method
Salting in and salting out
Using heavy metals
Chromatographic methods
Tricholoroacetic acid
Alcohol precipitation

Amino Acids and Their Properties

Structure

Central α-carbon attached to:

Amino group (-NH₂)
Carboxyl group (-COOH)
Hydrogen
Variable R group

20 standard amino acids

differ by R group

All are L-amino acids

Ellarum L aanu
except D-amino acids in bacterial cell walls

Glycine:

No chiral centre → optically inactive

Classification

By Side Chain

Group	Examples	Mnemonic / Note
Aliphatic	Gly, Ala, Val, Leu, Ile	ALI → GALVI
Branched	Val, Leu, Ile	VaLII
OH-containing ↳ Helps with covalent modification ↳ Binds Phosphate	Ser, Thr, Tyr	Sthree → 3 ”Oh” → told by STHreee
Sulfur-containing	Cys, Met	CM
Acidic	Asp, Glu	AG
Amides	Asn, Gln	Derivatives of AG
Basic	Arg > Lys > His	His Lies Are basic
Aromatic	Phe, Tyr, Trp	hTTP
Imino	Proline	Pyrrolidine ring Ninhydrin test → Yellow
Imidazole	Histidine	Buffer near pH 7

Sulphur containing

Cysteine	Methionine
S bonded to 1 C (H–S–C)	S bonded to 2 C (C–S–C)
Polar (–SH group)	Non-polar
Non-essential AA	Essential AA
Glucogenic AA	Glucogenic AA

By Polarity

Polarity	Amino Acids	Notes
Basic (Positive)	Arg > Lys > His	Arg = most basic; His uncharged at pH 7
Nonpolar	Ala, Val, Leu, Ile, Met, Phe, Trp, Pro	Isoleucine = most nonpolar I → Non Polar Pro ALVI Met Phe in a Trip al, le, la
Polar (Uncharged)	Ser, Thr, Asn, Gln, Cys, Gly, Tyr	visited Polar → C STAG
Acidic (Negative)	Aspartate, Glutamate	pKa ~4

ANS

By Nutritional Requirement

Type	Amino Acids	Mnemonic / Notes
Essential	Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys	Valli () Met () Phe () in a Trip () → His () three (threonine) Lies (Lysine)
Semi-essential	Arg, Tyr, Cys	Urge for Tyrions Sister → Semiessential
Non-essential	All others	Asp, Glu = acidic non-essential

Limiting Amino Acids

Food	LAA	Mnemonic
Cereals	Threonine & lysine	• Cereals in Thali • Siri told 3 () lies ()
Maize	Tryptophan & lysine	• Maize → goes in Trolly • Maise is Tryps () of Lies ()
Pulses	Cysteine & methionine	• Pulses → PCM • Pulses for CM ()

By Metabolic Fate

Category	Amino Acids	ㅤ
Glucogenic	All except Lys, Leu	ㅤ
Ketogenic	• Phe, Ile, Tyr, Trp • Lys, Leu (only purely ketogenic)	Aromatic + Isoleucine, Leucine, Lysine
Both	Phe, Ile, Tyr, Trp	I (Isoleucine) have smell (Aromatic) bcz I have both (Keto + Gluco)

Amino acid derivatives

Amino Acid	Biogenic Amines / Derivatives	ㅤ
Glycine	Sir () He () Created () Pure () Glittering () Salts () • Serine • Heme • Creatine • Purines (C4, C5, N7) • Bile salts • Glutathione • Collagen	• M/C AA in collagen • Simplest, optically inactive, flexible
Histidine	Histamine	Decarboxylation reaction (Vit B6)
Glutamic Acid	GABA (γ-aminobutyric acid)	Decarboxylation reaction (Vit B6)
Cysteine	Glutathione, Taurine	Sister () Glu (Glutathione) tuuri (Taurine)
Arginine	NO, Creatine, Ornithine, Urea Argentina ykk No (NO) creating (Creatinine) urea	• Most basic • NET → Neutrophil trap
Tyrosine	• Thyroxine • Tyramine • Norepinephrine, Epinephrine • Dopamine • Melanin	Dope (Dopamine) Black (Melanin) Tyre ()
Tryptophan	• Serotonin • Melatonin • Niacin	Try () Nice (Niacin) Tonics (Sero, Melo)
Lysine	• Cadaverine	Cadaver Lying
Serine	Precursor to • Glycine, Cysteine, Selenocysteine	Phosphorylated by Protein kinases
ㅤ	Forms • Phosphatidylserine, Choline, Betaine	Ser Beta (Betaine) ne Cola (choline) kudichenu Pottich (Phosphat)

Lipotropic

Choline, Lecithin, Methionine

NOT Arginine

Creatine Synthesis:

Requires 3 amino acids

Arginine, glycine, methionine (as SAM donor)

Create - 6 glizing metha

Glutathione (GSH)

γ-glutamyl-cysteinyl-glycine (GSH)

Tripeptide composed of:

Glutamic acid + Cysteine + Glycine

GSH + H2O2 → water + GS-SG (oxidised)

via Glutathione peroxidase (dep on Selenocysteine)

GS-SG (oxidised) → GSH (reduced)

Regenerating Enzyme: Glutathione reductase (dep on Vit B2)
Hydrogen source: NADPH.

Peroxide Protects and Reductase replenishes/regenerates

Functions

Important antioxidant for RBCs.
Free radical scavenger (Antioxidant role)

Glutathione peroxidase

Transport of ammonia

via Meister’s cycle / Gamma-glutamyl cycle

Conjugation of unconjugated bilirubin (detoxification reactions)??
Coenzyme role

Derived Amino Acids

Selenium

Daily requirement: 50–60 mcg/day

Functions as an important antioxidant

Selenocysteine:

21st amino acid
Coded by UGA (Stop codon)
Formed by co-translational modification
Serine → Selenocysteine
Found in:

Glutathione peroxidase

Protects against oxidative stress

Thioredoxin reductase

Redox balance in cells

Glycine Reductase
Deiodinase

Thyroid hormone conversion: T4 → T3

Selenoprotein P

Transports selenium in plasma

NOT GLUTATHIONE REDUCTASE (Dep on Vit B2)

”Mneumonic: Selena’s sister serena from UGAnda“
"Selena glue thinnu diarrhea aayi"

Pyrrolysine:

22nd Amino acid
Coded by UAG
From Lysine

Both 21 22 due to cotranslational modification

Stop Codons:

UAA
UGA (Selenocysteine)
UAG (Pyrrolysine)

Disorders

ㅤ	Disorder	Features	Management
Selenium deficiency	Keshan Disease	Dilated Cardiomyopathy, weakness, hypothyroidism	Selenium supplement
Selenium Toxicity	Selenosis - Alkali disease in cattle - Blind staggers	Hair/nail loss, garlic breath, diarrhea	Remove exposure

Derived

Seen in Proteins	Not Seen in Proteins
Hydroxyproline, Hydroxylysine (Collagen)	Ornithine, Citrulline, Argininosuccinate
γ-carboxyglutamate (Coagulation) [Vitmain K]	Homoserine, Homocysteine
Methyllysine (Myosin), Desmosine (Elastin)	—

Special Properties

Chirality

All (except Glycine) are chiral

Isoleucine, Threonine: have 2 chiral centers

2 centre for 3 () ice ()

Zwitter ion & Isoelectric Point

Buffering = Solubility = K

I shape → Precipitation

S shape → Solubility

With Single Ionizable groups

With Multiple Ionizable groups

All amino acids have atleast 2 functional ions

So could be biprotic or triprotic
NEVER Monoprotic

pK1 and pK2

Points of maximal buffering capacity

At pH 7.4, exist as zwitterions:

– NH₃⁺ and – COO⁻

pI (Isoelectric Point):

Net charge = 0

Point of minimal buffering capacity

Precipitation ↑, Solubility ↓, Buffering ↓

Basic AAs:

High pI → +ve at pH 7
His Lies Are Basic

Acidic AAs:

Low pI → –ve at pH 7

Buffering Capacity

Histidine:

Imidazole side chain → buffer near pH 7

Light Absorption at 280 nm

Amino Acid	Absorbs UV	ㅤ
Tryptophan	Highest	d/t Indole group ↳ Also answer Aldehyde based tests
Tyrosine	Moderate	ㅤ
Phenylalanine	Lowest	ㅤ

Protein Structure

Level	Description	Stabilizers	AA responsible	Methods
Primary	A-A sequence	• Peptide bonds	ㅤ	• Sanger’s sequencing • Edman’s sequencing • Reverse sequencing
Secondary	α-helix (M/c) β-sheet	• H-bonds	Glycine (β-turns) Proline (β-turns)	• Optical rotator dispersion • Ocular dichroism
Tertiary	3D folding	• H-bonds • Disulfide • Hydrophobic • Ionic	Cysteine	• X-ray crystallography • UV spectroscopy • NMR spectroscopy
Quaternary	Multi-subunit ↳ α chain ↳ β chain	Same as tertiary	ㅤ	ㅤ

Glycine:

Flexibility (β-turns)

Proline:

Kinks (β-turns)

Cysteine:

Disulfide bonds

Mnemonic: Pro Kinks (Proline → Kinks) are Greatly Flexible (Glycine → Flexibility)

Glycine and proline dont form alpha helix

due to lack of hydrogen

Screening for IEM

IOC / Gold standard: Tandem Mass Spectrometry:

Blood spot

Gas Chromatography - Mass Spectrometry:

Fresh Urine

High Performance Liquid chromatography/Electrophoresis:

Plasma, urine

Urine Odour and Diagnosis

Urine Odor	Inborn Error of Metabolism
Fruity	DKA
Maple syrup	Maple syrup urine disease
Swimming pool	Hawkinsinuria
Cat urine	3-Hydroxy-3-methylglutaric aciduria
Oast house	Methionine Malabsorption / Beer baby syndrome
Dried malt / hops like	Oasthouse syndrome
Sweaty feet	Isovaleric acidemia
Sweaty feet	Glutaric acidemia (type II)
Boiled cabbage	Hypermethioninemia
Cabbage	Tyrosinemia 1
Tomcat urine	Multiple carboxylase deficiency
Mousy/Musty	Phenylketonuria
Rotting fish	Trimethylaminuria aka Fish Odour Syndrome ↳ Avoid Choline ↳ Avoid cola with fishy smell

Homocystinuria

Cystinuria

Cystinosis

Homocystinuria

Enzyme Defect	Disorder
MAT	Primary hypermethioninemia
Cystathionine β-synthase	Classic homocystinuria
Cystathionase	Cystathioninuria
Methyline THF reductase	Non-classic homocystinuria
Defect in methyl B₁₂ formation	Non-classic homocystinuria

ㅤ	Type 1 → Classical	Type 2 → Non Classical
Enzyme deficiency	Cystathionine Beta synthase Homocysteine + Serine → Cystathionine → Cysteine	Methionine synthase Homocysteine → Methionine
Homocysteine	↑↑	↑↑
Cysteine	↓↓	N
Methionine	N	↓↓
Treatment	• Responds to B6 • Cysteine supplementation	• Responds to B12 and folate • Methionine supplementation

A disorder characterized by:

Fair complexion
Accelerated atherosclerosis and thrombosis.
Skeletal deformities

flat foot
Charlie Chaplin gait
Marfanoid habitus

Chest wall deformities

Subluxation of eyes

Inferomedial ectopia lentis

Stroke episodes

Hypercoagulable state

Differentiate from Marfans by

Fair complexion
Inferomedial ectopia lentis

Treatment:

Pyridoxine, folic acid
Restrict methionine
Supplement cysteine

Mnemonic: Pyramid (Pyridoxine supplementaion) nte mukalil keri thazhott (Inferomedial ectopia lentis) nokkum

Mnemonic: Homocysteine → 6

6 x 1 (Type 1) = 6 (B6)
6 x 2 (Type 2) = 12 (B12)

Cause	Subluxation	ㅤ
Blunt trauma	• M/c cause	ㅤ
Marfan’s syndrome	• Superotemporal	FAN → Upper
Homocystinuria	• Inferonasal	URINE → Infero
Weill-Marchesani syndrome	• Anterior • Microspherophakia	March forward → Anterior

Fates of Homocysteine:

Major fate (Conversion to Cysteine):

Homocysteine + Serine → Cystathionine

by Cystathionine Beta synthase (B6-dependent).
Cystathionine → Cysteine

Minor fate (Conversion to Methionine):

Homocysteine → Methionine,

by Methionine synthase.
Dependent on Methyl B12,

gets a methyl group from N5 Methyl THFA.

Differences Between Homocysteinuria & Marfan's Syndrome

Fair complexion

Seen in Homocysteinuria
Not in Marfans

(differentiates from Marfan)

Cystinuria

Due to a defect in a neutral amino acid transporter in the PCT.

Leads to decreased reabsorption of Cysteine, Ornithine, Lysine, Arginine (COLA)

Only Sister → Urge to Lie
Neutral COLA

These amino acids are excreted in urine.

Cysteine vs Cystine

Cysteine → has a Cys-SH group.
Two cysteine molecules → condense → form Cystine (disulfide bridge).
Excess Cysteine forms insoluble Cystine

Cystine is insoluble in urine.
Accumulates in renal tubules.
Leads to renal stones (cystine stones).

Obstructive uropathy.

Cystinuria in Urine detected with

sodium cyanide nitroprusside test
proton nuclear magnetic resonance spectroscopy

Cystinosis

Kidney (Fanconi → Polyurea) + Eye (shimmery cystine crystals + Photophobia)

A lysosomal storage disorder.

Caused by defective efflux of Cysteine from lysosomes.

Cysteine accumulates in lysosomes → Lysosomal degranulation →

Acidic pH is released into tissues
Leads to tissue degradation.

Damage to the PCT causes

Fanconi syndrome

Glycosuria, aminoaciduria, phosphaturia.
Bicarbonaturia, polyuria, polydipsia.

Local tissue damage in the iris causes:

Iris depigmentation.
Photophobia.

Slit lamp

shimmery cystine crystals in cornea.

Rx:

Cysteamine

NOTE: Different Fanconis

ㅤ	ㅤ
Fanconi disease/syndrome	• Proximal tubular reabsorption problem → Type 2 RTA • Glycosuria, aminoaciduria
Fanconi anemia (Not syndrome)	• Pancytopenia + radial ray
Fanconi Bickel syndrome	• Mutation in GLUT-2 • Bickel → Bi → 2 (GLUT 2) Defect in glucose sensing → ↓ insulin release • Postprandial Hyperglycemia. • Fasting Hypoglycemia • Glycogen accumulation disorder

VACTERAL
Holt - Oram (ASD + Radial Ray)
TAR (thrombocytopenia + absent radius)
Congenital torticollis → Cock robin position — VACTERAL
Holt - Oram (ASD + Radial Ray)
**TAR** (thrombocytopenia + absent radius)
Congenital torticollis → **Cock robin position**

Stranger things characters

Dustin (Cleido cranial dysplasia)

Robin (Cock robin position)

Ray (Radial Ray) Hopper (Holt Oram ASD)

Q. A 12-year-old boy presented with photophobia, short stature, polyuria and polydipsia. Slit lamp examination of the cornea is shown in the image. The probable diagnosis is:

A. Cystinuria

B. Cystinosis

C. Homocystinuria

D. Hartnup's disease

Phenyl Alananine & Tyrosine

Phenylalanine, Tyrosine, Tryptophan (Aromatic amino acids)

absorb UV light at 280nm

Phenyl Ketonuria

Alkaptonuria

Tyrosenemia

Q. A 20-year-old boy with severe mental retardation, mousy odour in body fluids, hypopigmentation. Patient has frequent episodes of seizures & aggressive behaviour. What is your diagnosis?

A. Tyrosinemia

B. Albinism

C. MSUD

D. Untreated PKU Phenylketonuria

ANS

Clinical presentation points to untreated phenylketonuria.

Q. A child presents with mental retardation, a characteristic odour and hypopigmentation along side is provided the result of Ferric chloride test that was done in his urine. The cause of the characteristic odour in the patient is:

A. Benzoquinone acetate

B. Phenyl pyruvate

C. Phenyl Acetate

D. Alpha hydroxy butyrate

ANS

Phenyl Acetate

Ass Smells

Phenylketonuria (PKU)

Mouse → Mousy odour
White guy → Fair skin

Cause:

Deficiency of phenylalanine hydroxylase

Tyrosine becomes essential

Clinical:

Hypopigmentation (fair skin (Blond), blue eyes)

D/t ↓↓ Tyrosine

Intellectual disability

by competing at BBB with other Neutral amino acids

Seizures
Mousy odor

↑↑ Phenyl acetate
Ass smells

Persistence of neurological symptoms

after phenylalanine restriction → Non-classic PKU

Lab

IOC: TMS
Positive Ferric chloride test

d/t Phenylpyruvate
Payaril () Iron (FeCl3) und
put Iron (FeCl3) in Fire (Pyruvate)

Guthrie’s test (Bacterial inhibition test) :

Growth of Bacillus subtilis.

Blood phenyl alanine levels
Enzyme studies.

Treatment:

Phenylalanine restricted diet
Synthetic tetrahydrobiopterin (THB)

in Non-classic PKU
Drug: Sapropterin dihydrochloride (Kuvan)

Large neutral amino acids supplementation

Tryptophan
Tyrosine

Phenylalanine embryopathy

↑ phenylalanine levels in

pregnant patients with untreated PKU

Features:

Fetal growth restriction,
microcephaly,
intellectual disability,
congenital heart defects

Prevention:

Dietary measures in pregnant women with PKU

Tyrosine

Condition	Symptoms	Enzyme defect	ㅤ
Tyrosinemia type II	Corneal ulcers, hyperkeratosis	TT	2 T → Type 2
Tyrosinemia type III	Mental retardation	PHPP	3 letter → Type 3
Alkaptonuria	Arthritis, black urine	Homogentisate oxidase	Blackaptonuria Black Human (Homoentisic acid))
Tyrosinemia type I	Liver and renal disease, cancer	Fumaryl acetoacetate Hydrolase	First → F

Question:

Q. An infant presented with watering of the eye, incessant cry and on observation tiny erosions were seen as shown in the image. The pediatrician also observed a rough palm in the infant. The probable diagnosis is

A. Type 1 Tyrosinemia
B. Type II Tyrosinemia
C. Type III Tyrosinemia
D. Alkaptonuria

Explanation:

Spontaneous corneal erosions + Palmar hyperkeratosis

indicate Occulocutaneous syndrome.

Occulocutaneous syndrome is Type II Tyrosinemia.

Tyrosine Metabolism

Phenylalanine hydroxylation becomes Tyrosine or Hydroxyphenylalanine.

Pathway:

Type-1 tyrosinemia (hepato renal syndrome):

Deficiency: Fumarylacetoacetate hydrolase.

Fumarylacetoacetate ↑↑↑ → Succinyl acetone ↑

Succinyl acetone causes

Hepatorenal syndrome

Liver and parenchymal cells

hypoglycemia
Jaundice
Hepatomegaly,
liver cirrhosis,
Hepatocellular carcinoma in young children

Renal parenchymal cells:

Initially causes Fanconi syndrome.
Progresses to Chronic kidney disease.

Inhibits delta ALA dehydratase.

Causes accumulation of ALA, which is toxic to neurons.

Patient presents with neuropsychiatric manifestations that mimic Porphyria (AIP)

Nitisinone:

Niithi Pulasrtan vendi → induce type 3 Tyrosinemia in Type 1 to avoid HCC

⛔ Para Hydroxy phenylpyruvate dioxygenase.

Indication for Type 1 Tyrosinemia:

Prevents formation of fumarylacetoacetate.

Succinylacetone will not accumulate.
Prevents decompensated liver disease or Hepatocellular carcinoma.

Also for

Hawkinsinuria
Alkaptonuria.

Type-II tyrosinemia
(Occulo cutaneous syndrome, Richner-Hanhart syndrome):

Deficiency: Tyrosine transaminase.

Mnemonic: Type 2 → 2 Ts (Tyrosine Transaminase)→ 2 eyes

Cutaneous: Palmar hyperkeratosis.

Palmoplantar Keratoderma seen in

Pityriasis Rubra Pilaris
Type 2 tyrosinemia
Arsenic poisoning

Ocular:

Painful corneal erosion

Corneal ulcers : Poorly stained with fluorescein.

Type-III tyrosinemia:

Deficiency: Para Hydroxy phenylpyruvate dioxygenase.

Mnemonic: 3P → PPP

Loss of function mutation

causes Type 3 Tyrosinemia.

Features: Recurrent seizures, intermittent ataxia.

Gain of function mutation

Partially active PHPP

causes hawkinsinuria → Swimming pool odour

Alkaptonuria (Black urine disease):

Mnemonic

HAO Blackaptonuria.
Black human → Homogensic acid

Deficiency: Homogentisate oxidase.

Homogentisic acid ↑↑ → benzoquinone acetate → polymerizes →
melanin-like fibrils / alkapton bodies

Fibrils accumulate :

Skin:

Pigmentation of

pinna, nose tip, thenar/hypothenar eminence,
mucus membrane.

Eye (Osler's sign):

Black/brown pigmentation

along the attachment line of medial and lateral rectus

(first sign).

Cartilage:

Causes cartilage destruction.
This leads to ochronosis / Ochronotic arthritis.

Intervertebral disc calcification,

Features:

Multiple joint involvement,
multiple intervertebral disc bulges.
Bamboo spine.
Vacuum phenomenon (Air space in vertebra).

Fibrils also accumulate in urine.

Urine turns dark on standing (first symptom).

Treatment: Nitisinone

It ⛔ Para Hydroxy phenylpyruvate dioxygenase.
Homogentisic acid does not accumulate.

note: Ochronosis:

seen in alkaptonuria, Hydroquinone, Carbolic acid ingestion

IV disc calcification

note: Garrod’s tetrad

Cystinuria

Alkaponuria

Albinism

Pentosuria

Albinism

Defect: Defect in tyrosinase

copper-containing enzyme

Mnemonic White tyre ( Albinism tyrosinase )

Features:

Milky white skin & hair

Photophobia

Lacrimation

Increased skin cancer risk

Nystagmus

Treatment:

Sun protection, visual aids

Tryptophan

Derivatives of Tryptophan

Drug causing Pellagra acting via Tryptophan

Isoniazid > Oral contraceptives

Induces Vitamin B6 deficiency → ↓Niacin → pellagra.

Azathioprine, 6-MP, 5-FU:

Inhibit tryptophan → niacin conversion → Pellagra
5, 6 Azad → Dont trty to be nice (Try ⇏ Niacin)

Carcinoid Syndrome

Carcinoids are tumors of neuroendocrine cells

Argentaffin cells / Kulchitsky cells of crypts of Leiberkuhn
Present in

Intestine
Brain
Platelets

↑↑ Serotonin → ↓Niacin

Most common site

Ileum > appendix (Tip) > jejunum
Most common tumor of the appendix

If liver metastasis (+) in Carcinoid tumor

⇒ ↓↓ metabolism of serotonin
⇒ Carcinoid syndrome (+)

Clinical Features

Serotonin enters circulation → Bronchospasm.
Features of pellagra
Intermittent diarrhea
Cutaneous flushing (m/c symptom)

go to bathroom and repeated flush (Cutaneous flushing)

Sweating
Abdominal pain, sweating.
Right heart valve involved:

Tricuspid Valve (m/c).

Investigations

24-hr urinary 5-HIAA ↑ (5-Hydroxy indole acetic acid)
Blood: Serum chromogranin.
Imaging:

CECT
Serotonin receptor Scintigraphy (localise tumour)

Management

Ki67: Proliferation Index marker.
Sx f/b Ki67 → ↑ levels:

Malignant NET → Require Chemo Rx.

Hartnup’s Disease

Hari - SSLC (SLC) kku padichapo "Ente monne pee-chi blue aayi!

Doctor paranju Hartnup aanennu! Tryptophan escape aakunnu apparently!"

Mutation

SLC6A19 mutation (Chr.5)

Transporter is in enterocytes and PCT cells.
Defect:

defective Neutral AA transporter
defective tryptophan transporter
↓
↓ Tryptophan absorption from the intestine and reabsorption in the kidney
↓

↓ Tryptophan

↓ Serotonin

↓ Niacin = Niacin deficiency = Pellagra like rash

indoxyl compounds in intestine
↓

Blue diaper syndrome - Due to indican (indoxyl sulfate) in urine
↓
Obermeyer test (indoxyl in urine)

↓ Tryptophan → ↓ Serotonin & ↓ Niacin

(60 mg tryptophan → 1 mg niacin)

Clinical Features

Asymptomatic (mostly)
Cutaneous photosensitivity (m/c symptom)
Accumulation of tryptophan in intestine → bacterial decomposition → indoxyl compounds → Indoles absorbed → excreted in urine as → bluish discoloration of diaper
Ataxia
Wide-based gait

Test

Obermeyer test

indoxyl in urine

Diagnosis:

HPLC

Neutral aminoaciduria

Treatment

Niacin, high protein diet
Lipid soluble tryptophan esters

Revise Epilepsy

Epilepsy	Characteristic EEG
GTCS	DOC • Phenytoin, Valproate
Absence / Petit mal	• Spike & wave (dome) pattern • 3 Hz spikes DOC • Ethosuximide, Valproate • Absent? → Ethuvo ? (Ethosuximide)
Infantile spasms	• Hypsarrhythmia Age • < 1 years DOC • without tuberous sclerosis: ACTH, Prednisolone • with tuberous sclerosis: Vigabatrin
Juvenile myoclonic Epilepsy (Janz)	• 4–6 Hz polyspikes & slow wave discharge • JME → JANZ S → 4-5 letters → 4 - 6 Hz polyspikes, slow Age • 10 - 19 years DOC • Valproate
Lennox Gastaut syndrome	• Slow (<3 Hz) spike wave complex • LGS → < 3Hz spike complex DOC • Valproate, Lamotrigine
Hepatic encephalopathy	• Triphasic wave {- wave → +ve wave → - wave}
1. SSPE → 8 years age 2. HIE 3 3. Comatose → (drug/severe hypothermia)	• Burst suppression
Prion disease (Kuru)	• Periodic sharp wave complexes Age • 35 years
HSV encephalitis	• Periodic lateralized epileptiform discharge • Affects temporal lobes • DOC: IV Acylovir • HSV → His Wife → Like temples (Period late)

SSLC / SCENE Genes

SCN/SLC	Disease	Features
SLC6A19	Hartnup’s Disease (Chr 5) 6 days Hearty trip	• Defect of tryptophan transporter • Cutaneous photosensitivity (m/c symptom) • Obermeyer test → indoxyl in urine Accumulation of tryptophan in intestine → bacterial decomposition → indoxyl compounds → Indoles absorbed → excreted in urine as indoxyl sulfate→ bluish discoloration of diaper
SLC2A1	GLUT 1 defect SSLC → 2 times → bcz brain hypoglycemia	↓ CSF glucose → seizures ↳ Rx: Pure ketogenic diet
SCN1A	Dravet syndrome ↳ defective Nav1.1 Na channel ↳ ⛔ GABA	Seizures ↳ DOC: Valproate
SCN5A (Loss of function)	Brugada syndrome ↳ defective Cardiac Na channel 1 Dragon drank 5 Bru	Brutal (Brugada) scene (SCN5A) guy like me (pseudo RBB) → drinking soda (Na channelopathy) → sudden seizure and death () Broad P wave → Long PQ seg → raised J point → coved ST → T inversion
SCNN1B/G genes	Liddle Syndrome ↳ Defect: ENaC channel	• AD inheritance • Hypertension + Pseudoaldosteronism • Hypokalemic metabolic alkalosis
Anti GM1 Antibody	Guillain Barre Syndrome (AIDP)	• Albumino-cytological dissociation • Earliest sign: Distal areflexia. • Bladder and bowel spared. • Bilateral ascending symmetrical flaccid paralysis. • Brighton Criteria for GBS
Anti GQ1 Antibody.	Miller Fisher Fish vangan Que nikkanam	Triad • Ophthalmoplegia (3rd nerve palsy). • Areflexia. • Ataxia.
anti P/Q antibody	Lambert Eaton Syndrome Eat 3, 4 Amino acid (3,4 aminopyridine) → gain strength → ↑↑ response	• Pre-junctional ↓↓ release of Ach at NMJ • Oat cell cancer lung → Paraneoplastic • Repetitive nerve stimulation test: ↳ Incremental response Treatment: • DOC: 3,4 aminopyridine • Pyridostigmine

Amino Acids & disorders

Amino Acids

Protein Precipitation

Amino Acids and Their Properties

Structure

Classification

By Side Chain

Sulphur containing

By Polarity

By Nutritional Requirement

Limiting Amino Acids

By Metabolic Fate

Amino acid derivatives

Lipotropic

Creatine Synthesis:

Glutathione (GSH)

Derived Amino Acids

Selenium

Disorders

Derived

Special Properties

Chirality

Zwitter ion & Isoelectric Point

pK1 and pK2

At pH 7.4, exist as zwitterions:

pI (Isoelectric Point):

Buffering Capacity

Light Absorption at 280 nm

Protein Structure

Screening for IEM

Urine Odour and Diagnosis

Homocystinuria

Differences Between Homocysteinuria & Marfan's Syndrome

Cystinuria

Cystinosis

NOTE: Different Fanconis

Q. A 12-year-old boy presented with photophobia, short stature, polyuria and polydipsia. Slit lamp examination of the cornea is shown in the image. The probable diagnosis is:

Phenyl Alananine & Tyrosine

Phenylketonuria (PKU)

Phenylalanine embryopathy

Tyrosine

Question:

Tyrosine Metabolism

Type-1 tyrosinemia (hepato renal syndrome):

Succinyl acetone causes

Nitisinone:

Type-II tyrosinemia(Occulo cutaneous syndrome, Richner-Hanhart syndrome):

Type-III tyrosinemia:

Alkaptonuria (Black urine disease):

Fibrils accumulate :

note: Ochronosis:

note: Garrod’s tetrad

Albinism

Features:

Treatment:

Tryptophan

Derivatives of Tryptophan

Carcinoid Syndrome

Hartnup’s Disease

Revise Epilepsy

SSLC / SCENE Genes

Type-II tyrosinemia
(Occulo cutaneous syndrome, Richner-Hanhart syndrome):