Metabolism Flashcards
Which glycogen storage disease has glycogen phosphorylase deficiency?
Type 5 (McArdle’s disease)
Which glycogen storage disease has glucose-6-phosphatase deficiency?
Type 1 (Von Gierke’s disease)
Which glycogen storage disease has lactic acidosis, hyperlipidemia, hyperuricemia?
Type 1 (Von Gierke’s disease)
Which glycogen storage disease has alpha-1,6-glucosidase deficiency?
Type 3 (Cori’s disease)
Which glycogen storage disease has an alpha-1,4-glucosidase deficiency?
Type 2 (Pompe’s disease)
Which glycogen storage disease has cardiomegaly?
Type 2 (Pompe’s disease) infantile type
Which glycogen storage disease has diaphragm weakness -> respiratory failure?
Type 2 (Pompe’s disease) adult type
Which glycogen storage disease has increased glycogen in the liver, sever fasting hypoglycemia?
Type 1 (Von Gierke’s disease)
Which glycogen storage disease has hepatomegaly, hypoglycemia, hyperlipidemia (normal kidneys, lactate, and uric acid)
Type 3 (Cori’s disease)
Which glycogen storage disease has painful muscle cramps, myoglobinuria with strenuous exercise?
Type 5 (McArdle’s disease)
Which glycogen storage disease has severe hepatosplenomegaly and enlarged kidneys?
Type 1 (Von Gierke’s disease)
What fuels are produced and used in the post absorptive period?
Glucose from liver glycogenolysis/ gluconeogenesis b/c there is no glucose left from your meal anymore.
Fatty acids from adipose tissue.
Brain, muscles and other tissue predominantly use glucose.
When does gluconeogenesis begin in the post-absorptive period? When does it become fully active?
Begins 4-6 hours after last meals.
Fully active when glycogen stores are depleted (10-18 hours after last meal).
How does the pattern of fuel production and usage change in early starvation (24 hours after last meal)?
Mainly gluconeogenesis (possibly a small amount of glycogenolysis).
Fatty acids from adipose tissue.
Brain predominantly uses glucose. Muscles and other tissues use some glucose some glucose but predominanly fatty acids. Brain and RBCs hog the glucose.
In intermediate starvation (48 hours after the last meal) how does the pattern of fuel production and consumption change?
Produced: glucose from liver gluconeogenesis, fatty acids from adipose tissue, ketone bodies from the liver.
Used: brain uses predominantly glucose but also some ketone bodies. Muscles and other tissues use predominantly fatty acids but also some glucose and ketone bodies.
What metabolic scenario favors the synthesis of ketone bodies?
Excess of acetyl CoA from fatty acid metabolism. When there is so much acetly CoA that it cant go thru TCA cycle, the rest of it will be broken down to ketone bodies.
True or false. The ketone bodies can be used by all body tissues including the brain?
False. RBCs need glucose, everything else can use ketone bodies.
What is the pattern of fuel utilization and production in prolonged starvation (5 days after last meal)?
Produced: glucose from liver gluconeogenesis, fatty acids from adipose tissue, ketone bodies from the liver.
Used: Brain uses predominantly ketone bodies. Muscles and other tissues use predominantly fatty acids and some ketone bodies. Whatever glucose is left will be used by RBCs.
Comparing an overnight fast to a 3 day fast, what percentage of energy comes from glucose and from ketone bodies?
Overnight: 95% from glucose (2/3 from glycogen breakdown, 1/3 from gluconeogenesis). 5% from ketone bodies.
3 day fast: 60% from ketone bodies (1/2 are betahydroxybutarate, 1/2 acetoacetate). 40% from glucose (most from gluconeogenesis).
What are the major regulatory enzymes of the citric acid cycle?
Citrate synthase (1st step), isocitrate dehydrogenase (rate limiting step). Alpha ketogluterate dehydrogenase (heavily regulate. Requires lots of coenzymes -> Tender loving care for nobody = Thiamine/ TPP, Lipoic acid, CoA, FAD, NAD)
What is the rate limiting enzyme for glycolysis?
PFK1 (phosphofructokinase)
What is the rate limiting enzyme for gluconeogenesis?
Fructose-1,6-bisphosphatase
What is the rate limiting enzyme for citric acid cycle?
Isocitrate dehydrogenase
What is the rate limiting enzyme for glycogenesis
Glycogen synthase
What is the rate limiting enzyme for glycogenolysis?
Glycogen phosphorylase
What is the functional role of S-adenosyl-methionine?
Transfers methyl (-CH3) groups. Used in the generation of phosphocreatine. Also important in the tetrahydrofolate, folic acid pathway. SAM is the methyl donor man. We use ATP and methionine to make SAM.
What is the activated carrier for glucose?
UDP glucose
What is the activated carrier for electrons?
FADH2 or NADH (or NADPH)
What is the activated carrier for CO2?
Biotin
What is the activated carrier for one-carbon units?
Tetrahydrofolate
What is the activated carrier for acyl groups
CoA, lipoamide
How many ATP are generated durng aerobic metabolism?
Malate shuttle -> 32 ATP. G3P shuttle -> 30 ATP. Anaerobic = 2 ATP + lactate molecule.
What are the possible products of pyruvate?
Acetyl CoA with pyruvate dehydrogenase. Lactic acid, alanine or oxaloacetate.
What are the irreversible enzymes involved in gluconeogenesis?
Pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase (rate limiting step), glucose-6-phosphatase
What is the primary energy source in a patient that has not eaten in 2 days.
Fatty acids
What is the equation for Gibbs free energy?
change in G = change in H - Temp x change in S.
**Arrange the following molecules from most exergonic with loss of phosphate to least exergonic with loss of pohosphate: adenosine monophosphate, adenosine triphosphate, phosphoenolpyruvate
PEP > ATP > AMP
A stressed physician comes home from work, consumes 7 or 8 shots of tequila in rapid succession before dinner and becomes hypoglycemic. Why?
Generation of a lot of NADH from alcohol breakdown (both alcohol dehydrogenase and acetylaldehyde dehydrogenase create NADH) causing pyruvate to be made into lactate and oxaloacetate to be made into malate. This causes lack of substrates needed for gluconeogenesis. Less gluconeogenesis occurs and you become hypoglycemic.
A woman commonly develops intense muscle cramps and darkening of her urine after exercise. What is her diagnosis?
McArdles disease (type V glycogen storage disease). Skeletal muscle glycogen phosphorlyase deficiency.
What are the essential amino acids?
PVT TIM HALL Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histadine Arginine Leucine Lysine
What is the mechanism of action of lactulose?
Degrade by gut bacteria to acidify the GI tract and trap ammonium there (converts ammonia into ammonium anion). Also helps pull ammonium from the blood into the GI tract.
What amino acid is a precursor to histamine?
Histadine
What amino acid is a precursor to porphyrin, heme
Glycine
What amino acid is a precursor to nitric oxide
Arginine
What amino acid is a precursor to GABA
Glutamate
What amino acid is a precursor to S-adenosyl methionine (SAM)?
Methionine
What amino acid is a precursor to creatine?
Arginine
Compare carbamoyl phosphate 1 to carbamoyl phosphate 2.
Carbamoyl phosphate 1- in mitochondria. Urea cycle. Nitrogen source = ammonium.
Carbamoyl phosphate 2- in cytosol. Pyrimidine synthesis. Nitrogen source = glutamine
Rate limiting enzyme of the urea cycle
Carbamoyl phosphate synthetase I (CPS I)
Rate limiting enzyme of the hexose monophosphate pathway
Glucose 6 phosphate dehydrogenase
Rate limiting enzyme of fatty acid synthesis
Acetyl CoA carboxylase
Rate limiting enzyme of beta oxidation of fatty acids
Carnitine acyl transferase
Rate limiting enzyme of ketone body synthesis
HMG CoA synthase
Rate limiting enzyme of cholesterol synthesis
HMG CoA reductase
Rate limiting enzyme of bile acid synthesis
7 alpha hydroxylase
Rate limiting enzyme of heme synthesis
Aminolevulinate synthase
What deficiency causes familial hypercholesterolemia?
LDL receptor
A patient with PKU should have a diet low in phenylalanine. What other dietary modification should a patient with PKU make.
Increase dietary intake of tyrosine. Supplement BH4 (tetrahydrobiopterin) cofactor
A full term neonate becomes mentally retarded and hyperactive and has a musty odor. What is the diagnosis?
PKU
A two year old girl has an increase in abdominal girth, failure to thrive, and skin/ hair depigmentation. What is her diagnosis?
Kwashiorkor
A middle aged man has dark spots on his sclera and has noted that his urine turns black when left sitting for a period of time. What is the diagnosis?
Alkaptonuria
A patient has a genetic disease in which the treatment includes protein restriction to prevent mental retardation, ketoacidosis, and death. What is the diagnosis?
Maple syrup urine disease
A 18 year old female has moderate generalized abdominal pain, normal WBC, and no fever. She has parasthesias in her lower extremities. What is her diagnosis?
Acute intermittent prophyria
A 45 year old male alcoholic gets blistering lesions in sun exposed areas, especially the dorsum of the hands. He also has hypertrichosis of the face. What is the diagnosis?
Porphyria cutanea tarda
What is the treatment for homocystinuria?
Decrease methionine and increase cystine in the diet. Increase B6, B12, and folate in the diet.
