FATTY ACID 3 Flashcards
Explain with biochemical reasons, the statement ‘Fats are burnt in the flame of
* carbohydrates’
- Depleting CHO decrease pyruvate production during glycolysis.
- Diminished pyruvate further reduces TCA cycle intermediates,slowing TCA cycle activity.
- FA degradation in TCA cycle depends on sufficient OAA availability to combine with the acetyl CoA formed during b-oxidation.
- When the CHO level decreases, the OAA level may become inadequate and reduce fat catabolism.
- In this sense fats burn in a CHO flame.
Mention the significance of alpha oxidation
- Oxidation of Phytanic acid (branched chain FA, product of chlorophyll metabolism, dairy products, animal & fish fat)
- It has a methyl group on β– carbon atom & hence cannot under go β-oxidation & undergoes α–oxidation initially
Mention the significance peroxisomal oxidation of fatty acids
notes
Zellweger’s syndrome/ cerebro-hepato-renal symptom
enzyme deficiency: inherited absence of peroxisomes
Acc of: very long chain polyenoic FAs in brain
symptoms: neurological
signs: dysmorphic faces, progressive degenaration of brain/liver/kidney with death, retinal dystrophy, hearing loss
diagnosis: VLCFAs test, gene test
Refsum’s disease
genetic Deficiency of peroxisomal Phytanoyl CoA hydroxylase (PhyH)
* Accumulation phytanic acid in plasma & tissues
* Neurological damage:defective functioning of the olfactory and auditory nerves and cardiac malfunction
* Treatment : dietary restriction to halt disease progression
Jamaican vomiting sickness
cause: eating unriped ackee fruit
-contain hypoglycin A
-hypoglycin A inhibits acyl co A dehydrogenase
- beta oxidation of FA is blocked
symptoms: severe hypoglycemia, vomiting, convulsions, coma, death
Sudden infant death syndrome (SIDS)
deficiency: medium chain length acyl Co A dehydrogenase
decrease: in beta oxidation medium chain length FA( main E source in newborn)
effect: sudden death of infants
Carnitine deficiencies
Primary carnitine deficiency
caused by :defects in a membrane transporter that prevent uptake of carnitine by cardiac and skeletal muscle and the kidneys, causing carnitine to be excreted.
Treatment: carnitine supplementation.
Secondary carnitine deficiency
by: defects in fatty acid oxidation
acc: acylcarnitines (excreted in the urine, decreasing carnitine availability)
Acquired secondary carnitine deficiency
-in patients with liver disease (decreased carnitine synthesis) or those taking the antiseizure drug valproic acid
CPT deficiencies
CPT I deficiency
- CF: appear during early childhood.
- hypoketotic hypoglycemia
- Hepatomegaly liver failure.
- Elevated levels of carnitine in the blood.
- CNS damage,
- Seizures,
- Coma
- Sudden death.
CPT2 Deficiency
-Mutations in the CPT2 gene( autosomal recessive)
* 3 main types of CPT2.
* lethal neonatal form
* severe infantile hepatic cardiovascular form
* myopathic form
* Neonatal and infantile forms :severe multi-systemic diseases ,hypoketotic hypoglycemia , and low blood sugar, cardiomyopathy, seizures, and early death
* Myopathic form: exercise-induced muscle pain and weakness and occasional myoglobinuria.
Treatment: avoidance of prolonged fasting and a low-fat and high-carbohydrate diet
Tay-Sach’s disease- enzyme defect, substrate accumulating and findings
-deficient enzyme: hexosamidase A)
-Accumulation of GM2 gangliosides in the brain.
- Inheritance is autosomal recessive
-Children( symp show aft 6 months)
-progressive cognitive and motor deterioration resulting in seizures, intellectual disability, paralysis, and death by age 5 years. A cherry-red macular spot
Gaucher’s disease- enzyme defect, substrate accumulating and findings
-chronic rare inherited disorder that worsens over time.
-lack beta glucosidase enzyme
- accumulation of glucocerebrosides
- symptoms: marked splenomegaly, easy bleeding, delayed puberty, growth retardation, macrophage acc in liver,spleen, bone marrow
Niemann-Pick disease- enzyme defect, substrate accumulating and findings
-deficiency: acid sphingomyelinase
-acc: spingomyelin
A:large abdomen,cherry red spot eye, dysphagia,ataxia,rapid decline
B: abdominal swelling,no brain or nervous system involved
Farber’s disease- enzyme defect, substrate accumulating and findings
- X-linked lysomal storage disorder
- deficiency: α-galactosidase A
- acc: ceramide trihexosides
- Hypohydrosis since early childhood
- generalised telangiectasias including the palms, soles
paraesthesia in extremities - cataracts
- death due to kidney/heart failure
delayed puberty.
-Urine analysis:occasional maltese cross globules on polarising microscopy.
Skin biopsy:angiokeratoma α-galactosidase
sphingolipid degradation
notes
Metachromatic leukodystrophy
-dysmyelinating disease
- deficiency: arylsulfatase A enzyme
- acc: Galactosyl-3-sulfatide
-accumulated material will change the color (metachromasia) of acidified cresyl violet stain from violet to brown in tissue.
- mental retardation
- peripheral neuropathy
-death within 10 years
