Metabolic Flashcards
What enzyme converts D-Glucose -> Glucose-6-phosphate
Hexokinase
How many molecules of ATP and NADH and pyruvate are made via glycolysis
2 net molecules ATP (2 required, 4 produced)
2NADH
2 Pyruvate molecules
What enzyme converts pyruvate to lactate
Lactate dehydrogenase
What enzyme converts pyruvate to alanine
Alanine transaminase
Which GLUT transporter transports glucose to the brain
GLUT1
What GLUT transporter transports glucose to muscle and fat
GUT4
What glucose transport transports glucose to kidney/liver/pancreas
GLUT 2
What enzyme converts glucose –> glucose 6 phosphate
Hexokinase
What base molecule makes up glycogen and what does it connect to
Gluogenin
UDP Glucose
Which enzyme elongates the glycogen chain
Glycogen synthase
In a glycogen molecule
-what enzyme makes branches and what is the bond
-what enzyme elongates the chain and what is the bond
-Branching enzyme; a1-6 glycosidic bond
-Glycogen synthase; a1-4 glycosidic bond
What enzyme converts Glucose1phosphate to Glucose-6-phosphate
Phosphoglucomutase
What enzyme allows Glucose-6-phosphate to be relased into the blood
What organs is it found
What organ is it NOT found in
Glucose-6-phosphatase
Liver/Kidney/GIT
Not found in muscle
What pathway is used in the liver and RBC for glucose metabolism and to protect against oxidate stress
Pentose Phosphate pathway
What glycogen storage defect is due to a deficiency in glucose-6-phosphotase
von Gierke Disease- type 1
What causes Glycogen storage disease type 1: von Gierke disease and what are the symptoms
Glucose-6-phosphatase enzyme deficiency
Cannot convert G-6-P to free glucose so G-6-P builds up in cells
-hypoglycaemia
-G-6-P is shunted down glycolysis pathway to make pyruvate. Pyruvate converted ot
-Lactate (LDH)
-Alanine (ALT)
-Fatty acids –> hyperlipidaemia
Also get increased shunting of G6P down the pentose phosphate pathway –> increased purine synthesis –> increased uric acid
Conclusion
-Hypoglycaemia
-High lactate
-hyperlipidaemia
-Hyperalbuminaemia
-High uric acid
What can Glucose-6-phosphate become
glucose
Glycogen
Pyruvate–> alanine, fatty acids, lactate
Pentose phosphate pathway –> purine and pyridines –> urate
What features would you see in a child with GSD Type 1
what features on investigations
Hypoglycaemia –> seizures
Hepatomegally
Doll like facies + thin limbs
FTT
Investigations
-low BSL
-high lactate
-high alanine
-hyperlipidaemia
-hyperuraemia
-Liver biopsy: universal distension of hepatocytes with glycogen and fat
What foods should be avoided in von Gipple disease
Fructose
Galactose
What is the role of glucose-6-phosphate translocase
Glucose 6 phosphate is taken up into the ER
Dephosphorylated to glucose by glucose-6-phosphatase
Glucose-6-phosphate translocase allows the transport of G6P into the endoplasmic reticulum
SLCA gene is associated with what glycogen storage disease defect
GSD Type 1b: Glucose-6-phosphate translocase deficiency
What distinguishes type 1a via type 1b glycogen storage disease
Type1a= Von Gierke Disease- glucose-6-phosphatase deficiency
Type1b = Glucose-6-phosphate transferase deficiency due to SLCA gene
Both have accumulation of Glucose-6-phosphate –> hyperalanine, hyperlipidaemia, high lactate, hypoglycaemia
Type1b also has neutropenia and manage as per type 1a but also use prophylactic cotrimoxazole
hypoglycaemia, lactic acidosis, hyperuricemia, hyperlipidaemia
what is the disease
Glycogen storage disease type 1a or b
What is Pompe a disease of what enzyme
Where does glycogen accumulate
What are the symptoms
Pompe= GSD type 1
-disease of acidic alpha glucosidase (to break a1-4 and a-1-6 glycosidic binds)
-Accumulates in the liver and in muscle (skeletal, heart and smooth muscle)
Sx
-Hepatomegaly/ liver enlargement likely 2 to heart failure
-Cardiac: enlarged heart, Hypertrophic cardiomyopathy
-Skeletal: hypotonia, proximal myopathy in juvenile disease
-Smooth muscles of blood vessels and organs
-Enlarged tongue
Involvement of the diaphragm can cause respiratory distress
An infant presents with an enlarged heart and hypotonia/weakness
What metabolic disorder does this suggest
Pompe disease
What deficiency is present in Coris disease
What type of disorder is it
What are the symptoms
Deficiency of debranching enzyme
Glycogen storage disease
Sx: mild hypoglycaemia, hepatomegaly, skeletal muscle wasting and weakness, short stature
What is McArdle syndrome
What symptoms does it cause
What is the test for it
What is the treatment
A glycogen storage disease due to muscle phosphorylase deficiency
-Symptoms: cannot utilise glycogen so muscle fatigue with a second wind aka more energy once fatty acid is utilised
-test: ischaemic forearm test.
-Pretest venous CK/Ammonia/lactate
-inflate a blood pressure cuff to force arm to use glycogen and get person to do repetitive movements
-repeat ammonia/CK/lactate at 5, 10 and 20 min mark
-post test urine myoglobinuria
Treatment
-Avoid statins
-Pre work out protein and surcose
-Activity modification
What enzymes are responsible for converting galactose to Glucose 6 phosphate
Galactose kinase (Galactose –> Galactose-1-phosphate)
GALT (Galactose-1-phosphate-urodyltransferase)= Gal-1-Phosphate + UDP-Glucose –> Glucose-1-phosphate + UDP-Galactose
-UDP-Galactose Epimerase: converts UDP-Galactose –> UDP-Glucose
-Phosphoglucomutase = converts Glucose-1-phosphate –> Glucose-6-phosphate
What 3 enzymes cause galactosemia and what are the symptoms of each
1) GALT (Galactose-1-phosphate uridyltransferase) -
-onset of sx within a week due to milk consumption (lactose= glucose + galactose)
-E. coli sepsis
-lethargy
-jaundice
-coagulopathy
-oil drop cataracts
-faltering growth, tubulopathy, rickets
2) Galactosekinase- cataracts is the only issue
3) UDP-Galactose epimerise - only affects RBC
What 3 enzymes cause galactosemia and what are the symptoms of each
1) GALT (Galactose-1-phosphate uridyltransferase) -
-onset of sx within a week due to milk consumption (lactose= glucose + galactose)
-E. coli sepsis
-lethargy
-jaundice
-coagulopathy
-oil drop cataracts
-faltering growth, tubulopathy, rickets
2) Galactosekinase- cataracts is the only issue
3) UDP-Galactose epimerise - only affects RBC
What is deficient in Hereditary Fructose Intolerance
What sx does it cause
What is the treatment
Aldolase-B deficiency
F=Vomitting/hypoglycaemia on ingestion of fructose approx 6 months of age. Chronic= faltering growth, hepatomegaly, proximal renal tubulopathy
Investigations
-Reducing substances in urine
-Lactic acidosis
-Deranged LFTs and coagulation studies
Management: Avoid Fructose + Sucrose + Sorbitol
E. coli Sepsis and cataracts in a neonate is associated with what error of metabolism
Galactoseaemia
What deficiency results in phenylketonuria
Deficiency in phenylalanine hydroxylase OR biopterin deficiency
What amino acid is phenylalanine converted to
tyrosine
what is the amino acid tyrosine used in
protein synthesis
cathecolamine synthesis
thyroxine
melanin
What symptoms does PKU caused if left untreated
microcephaly
mental retardation
spastic cerebral palsy
albuminism
widely spaced teeth
musty odor
eczematous rash and dry skin
A baby has elevated succinylacetone- what is this pathopnemonic of
Tyrosinaemia
Tyrosine is covered to Fumerate and acetoacetate by fumaryl-acetoacetate. If this enzyme is deficient it is shunted to succinylacetone
What are the symptoms of tyrosinaemia
-peripheral neuropathy
-acute liver failure
-proximal renal tubulopathy
What is Maple syrup urine disease a deficiency of
Branched chain a ketoacid dehydrogenase
What effects does a deficiency in branched chain a-ketoacid dehydrogenase deficiency have
-high leucine –> outcompetes other amino acids to cross the BBB.
-In the brain, uses glutamine and alanine to convert back to other amino acids
-result = like glutamine = low GABA and glutamate (neurotransmitters) = impaired cell-cell communication
Also get elevated a-ketoacids which impair the kerbs cycle resulting in reduced ATP production
-Na/K ATP pump dysfunciton
-Cerebral oedema
what deficiency is present in homocysteinuria
what symptoms does it cause
what vitamins are given to help
if the vitamins don’t work what is given
cystathionine-b-synthetase
Sx
-marfanoid like sx
-ectopic lentis- downward
-intellectual disability
-blood clots as homocysteine inflames endothelium
-behavioural issues
-osteoporosis
Vitamin B6
Folate
BETANINE - think making homocystINI Better –> Better-nine
what is the role of glycine in the brain and spinal cord
acts as a neurotransmitter
-in the brain: excitatory effect
-spinal cord and brainstem: inhibitory affect
Canavan disease is a deficiency in Aspartoacylase (ASPA) which results in the accumulation of N-acetyl-L-aspartate
Why does this cause disease pathology
what are the symptoms
N-acetyl-L aspartate are converted to L-Aspartate and acetate by the enzyme Aspartoacylase.
Acetate converted to Acetyl-CoA and used in fatty acid synthesis in the myelin sheath
Defect - interfers with white matter tract
Result= leukodystrophy
Symptoms
-Regression of motor skills
-Macrocephaly (think child with a caravan on top of their head)
-hypotonia
-seizures
-paralysis
-blindness
what enzyme is deficient in propionic acidaemia
What treatment is used
propionyl CoA dehydrogenase
Tx
-L) carnitine
-Liver transplant
-Biotin
-Metronidazole
A child has bilateral subdural and encephalopathy
what metabolic condition should be excluded
what enzyme is deficient
Glutaric aciduria Type 1
Glutaryl-CoA-dehydrogenase
What metabolic condition causes this and why
Hartnup disease - cannot absorb tryptophan which forms niacin (B3) and serotonin so you get Pellegra (dermatitis, dementia, diarrhoea)
What is the pneumonic of the urea cycle
/ what is the urea cycle
“ Carbs combine with oranges to make a citrus appetizer that makes you full argaine but Urea continue to crave oranges”.
Carbomoyl phosphate + Ornithine Citrulinne Arginosuccinate Fumrate + Arginine Ornithine + urea
What is the role of carnitine in fatty acid oxidation
What defects are involved in defects of fatty acid oxidation
transports LCFA into the mitochondria
All are Medium/Short/Long/Very long CoA dehydrogenase defects
