Biochem - Metabolism Flashcards
Which pathway (Glycolysis or Gluconeogenesis) are more active if there is:
a. High levels of Fructose-1,6-Biphosphate
b. Low levels of Fructose-1,6-Biphosphate
a. Glycolysis
b. Gluconeogenese
Pyruvate Dehydrogenase Complex Deficiency
- How does it present?
- Why?
- Lactic Acidosis
- Neurologic defects
- increased serum alanine
- Since there is no pyruvate dehydrogenase, pyruvate will not be able to be converted into acetyl-coA and enter the TCA cycle so instead, this buildup of pyruvate will be shunted into the lactic acid and alanine pathways of pyruvate
What is the treatment for Pyruvate Dehydrogenase complex deficiency and why does it work?
Increased intake of ketogenic nutrients (lysine and leucine)
Metabolism of ketogenic amino acids (lysine and leucine) can provide energy in the form of acetyl-coA without increasing lactate production
What are the 4 possible fates of pyruvate?
- Acetyl-CoA (TCA cycle)
- Oxaloacetate (Gluconeogenesis)
- Alanine
- Lactate (anerobic glycolysis)
Pyruvate —-> Alanine
What enzyme is responsible?
What cofactors are required?
Alanine Aminotransferase
cofactor: B6
Pyruvate —-> Oxaloacetate
What enzyme is responsible?
What cofactors are required?
Pyruvate Carboxylase
cofactor: Biotin (B7)
Pyruvate —-> Acetyl-CoA
What enzyme is responsible?
What cofactors are required?
Pyruvate Dehydrogenase
cofactor: B1, B2, B3, B5, lipoic acid
Pyruvate —-> Lactate
What enzyme is responsible?
What cofactors are required?
Lactic Acid Dehydrogenase
cofactor: B3
Lactate Dehydrogenase Deficiency
- How does it typically present?
- Why?
1.
Exercise intolerance
(Muscle fatigure, pain, cramps with exercise)
2.
They cannot produce lactate and therefore lack anaerobic glycolysis
(LDH is needed to regenerate NAD+)
Pyruvate Kinase Deficiency
- How does it present?
- Why?
Hemolytic anemia with splenomegaly
Pyruvate Kinase converts Phosphoenylpyruvate into Pyruvate while generating 1 ATP in the process.
RBC’s dont have a mitochondria so they heavily rely on this enzyme for energy.
alpha ketoglutarate dehydrogenase
- What reaction does it catalyze?
- What cofactors does it require?
1.
alpha-ketoglutarate —-> Succinyl-CoA
2.
B1, B2, B3, B5, Lipoic acid
(same as pyruvate dehydrogenase)
Which reaction in the Krebs cycle generates GTP?
What is it needed for?
Succinyl-CoA —–> Succinate
GTP is required by Phosphoenylpyruvate Carboxykinase (oxaloacetate –> phoesphoenylpyruvate) in gluconeogenesis
What reaction in the Krebs cycle generates FADH2?
What cofactor is needed for this reaction?
Succinate —(succinate dehydrogenase)—> Fumarate
Cofactor: B2 (riboflavin)
What are the 2 reactions of the HMP shunt?
1. Glucose-6-Phosphate
—(Glucose-6-phosphate dehydrogenase)—>
6-phosphogluconolactone
2. Ribulose-5-Phosphate
—–(transketolase + B1 cofactor)—->
Fructose-6-Phosphate
What is the main function of the HMP shunt?
To make NADPH for:
- glutathione reduction inside RBCs
- Fatty acid synthesis
- cholesterol synthesis
Note: it also make some ribulose for nucleotide synthesis
Essential Fructosuria
- Deficient/defective enzyme
- Symptoms
- Fructokinase
- Asymptomatic
(other than fructose in urine)
Why is essential fructosuria asymptomatic?
Since Hexokinase will take over for fructokinase and convert Fructose into Fructose-1-Phosphate
Hereditary Fructose Intolerance
- Deficient Enzyme
- Symptoms
1. Aldolase B
(converts Fructose-1-P into either DHAP or Glyceraldehyde)
- Hypoglycemia, Jaundice, Cirrhosis, Vomitting
Why does Hereditary Fructose Intolerance result in hypoglycemia?
Since there is deficient aldolase B, there will be an accumulation of Fructose-1-Phosphate
Phosphate will become less available and gluconeogenesis and glycogenolysis will become inhibited
What sugar does the following tests test for:
1. Urine Dipstick Test
2. Copper Reduction Test
- Glucose
- All sugars (glucose, fructose, galactose)
What would be the recommended treatment for a patient with Hereditary Fructose Intolerance?
Decreased intake of:
- fructose
- sucrose (fructose + sucrose)
Galactokinase Deficiency
- What enzyme is deficient? What accumulates?
- Symptoms
- Galactokinase —> Accumulation of Galactitol
2.
Galactosemia + Galactosuria
Infantile Cataracts
Failure to track objects
Failure to develop a social smile
Classic Galactosemia
- Deficient Enzyme and accumulated substance
- Symptoms
1. Galactose-1-Phosphate Uridyltransferase
(Accumulation of Galactose-1-Phosphate and Galactitol)
- Severe Galactosemia
Failure to thrive + intellectual disability
Jaundice + Hepatomegaly
Infantile Cataracts
Fill in the blanks
Glucose ——-(?????)—–>
Sorbitol —–(?????)—–>
Fructose
Aldose Reductase
Sorbitol Dehydrogenase
Why do some cells convert glucose to sorbitol and then to fructose?
How can this be dangerous?
It is an alternative method of trapping glucose in the cell
Some cells lack sorbitol dehydrogenase which can result in sorbitol accumulation in the cell which can cause osmotic damage
Which types of tissue are most susceptible to osmotic damage due to sorbitol accumulation?
Lens —> cataracts
Retina
Kidney
Schwann Cells —> peripheral neuropathy
“Sorbitol LuRKS”
What are the Glucogenic amino acids?
Methionine
Histidine
Valine
“I met his valentine, she is sweet/glucogenic”
What are the ketogenic amino acids?
Lysine
Leucine
What are the acidic amino acids?
What are the basic amino acids?
Acidic:
Aspartic Acid & Glutamic Acid
Basic:
Histidine, Arginine, Lysine
Arginase Deficiency
- What cant be produced?
- How does it present?
1.
Urea and Ornithine
(from arginine)
2.
abnormal gait + growth delay
Which amino acid transports ammonia (NH3) to the liver so it can enter the urea cycle?
Alanine
Hyperammonemia
- What are the 2 main ways it can occur?
- Pathophysiology
1.
- Liver disease
- urea cycle enzyme deficiencies
2.
Excess NH3 depletes Glutamate (GABA) which disrupts neurotransmission
Hyperammonemia
- How does it present?
- Treatment
- Asterixis (flapping wrist tremor)
- Somnolence (desire to sleep)
- vomitting
-tachypnea
- cerebral edema
Treatment: limit protein in diet (so there is less a.a. catabolism)
Ornithine Transcarbamylase deficiency
- What cannot be produced?
- What substance builds up?
1.
Citruline cannot be produced from ornithine and carbomyl phosphate
2.
Carbomyl phosphate builds up which gets converted to
orotic acid
Ornithine Transcarbamylase Deficiency
- How does it present?
- What is found in blood and urine?
- Symptoms of hyperammonemia
(asterixis, sleepiness, vomitting, tachypnea, confusion)
- Orotic acid
(found in blood and urine)
Phenylketonuria (PKU)
- What deficiencies result in PKU?
- What amino acid becomes essential?
1.
- Phenylalanine Hydoxylase
(converts Phenylalanine to tyrosine)
-
BH4 (cofactor for phenylalanine hydroxylase)
2. Tyrosine
Phenylketonuria (PKU)
- How does it present?
- Treatment
1.
- Musty body odor
- fair/pale complexion
- intellectual disability
- seizures
- Increased tyrosine, decreased phenylalanine
Maternal PKU
- Why does it occur?
- How does the infant present?
- Mother lacks proper dietary therapy during pregnancy
- Infant presents with:
- microcephaly
- intellectual disability
- growth retardation
- congenital heart defects
Alkaptonuria
- What enzyme is deficient?
- What substance accumulates?
- Homogentisate Oxidase
(converts Homogentisic Acid to fumarate which enters TCA)
- Homogentisic Acid
Alkaptonuria
- How does it present?
- What are the urinary findings?
- Bluish/black connective tissue, sclerae and ear cartillage
- Urine turns black on prolonged exposure to air
Maple Syrup Urine Disease
- What enzyme is deficient?
- What cofactor is needed for that enzyme?
- What proteins cannot be broken down?
- Branched-chain alpha-ketoacid dehydrogenase
- Thiamine (B1)
3. Branched amino acids
(isoleucine, leucine, valine)
“I Love Vermont maple syrup from B1ranched trees“
Maple Syrup Urine Disease
- Presentation
- Treatment
1.
Urine smells like maple syrup / burnt sugar
Vomitting
Poor feeding
- restrictiction of isoleucine, leucine and valine
Thiamine (B1) supplementation
Deficiency of which 2 different enzymes can result in Homocystinuria?
- Cystathionine Synthase Deficiency
(homocysteine –> cystathione –> cysteine)
- Methionine Synthase Deficiency
(homocysteine —> methionine)
How does Homocystinuria clasically present?
Homocystinuria
Osteoporosis
Marfanoid Habitus
Occular changes (eyes downward and inward)
Cardiovascular effects (thombosis and atherosclerosis)
kYphosis
“HOMOCYsteinuria”
What does homocystinuria often result in cardiovascular events such as MIs and strokes?
Homocysteine is prothombotic
Cystinuria
- Where in the kidney does the defect occur?
- Which substances cannot be absorbed?
- What is the diagnostic test?
- Proximal Convoluted Tubule (PCT)
- Cystine, Ornithine, Lysine, Arginine
“COLA”
- Urinary cyanide-nitroprusside test
How do cystine stones appear on microscopy? Gross visual appearance?
Hexagonal shaped
“SIXtine stone“
Staghorn Calculi
(most commonly in children)
