Metabolism Flashcards
Liver prefers to use:
- fatty acids
- glucose
- amino acids
Adipose Tissues prefer to use:
fatty acids
Skeletal Muscle prefers to use:
- fatty acids at rest
- glucose on exertion
Heart Muscle prefers to use:
Fatty acids
Brain prefers to use:
- Glucose in fed state
- Ketone bodies under starvation
Dry calories in carbohydrates
4 kcal/g
Dry calories in proteins
4 kcal/g
Dry calories in fat
9 kcal/g
Glycogenolysis
Breakdown of glycogen to glucose
Glycolysis
single glucose into 2 pyruvate, 2 molecules of NADH, 2 ATP and 2 H20
Gluconeogenesis
generation of glucose from non-carbohydrates
Glycogenesis
Formation of glycogen from glucose
Insulin does what?
- promotes glycolysis and Pentose Phosphate pathways
- promotes glycogen formation
- inhibits gluconeogenesis in liver
Where can Hexokinase and Glucokinase be found?
- hexokinase = all cells
- glucokinase = pancreas & liver
What inhibits Hexokinase?
Glucose 6 phosphate
What inhibits Glucokinase?
Fructose 6 phosphate
What increases Glucokinase activity?
Glucose
What are their Km values? Which one can be saturated?
- Glucokinase = Km 20
- Hexokinase = Km 5
- Hexokinase can be saturated
Pyruvate Carboxylase genetic deficiency
- increase in Alanine, Lactate, and Pyruvate blood levels
- Diagnosis = developmental delays, recurrent seizures, and metabolic acidosis
Pyruvate dehydrogenase complex
- requires vitamins (Thiamine, Riboflavin, and Niacin
- Not regulated by glucagon or epinephrine
Lactate dehydrogenase (LDH) Deficiency
- unable to convert Pyruvate to Lactate
- NAD+ becomes limiting during exercise
- glyceraldehyde dehydrogenase flux reaction is inhibited
NAD+ levels are regenerated through what pathways?
- LDH
- Malate Aspartate shuttle
- Glycerol Phosphate shuttle
Galactosemia
Small Group problem
Glucose 6 Phosphate Dehydrogenase
Place holder
Fine Control of Citric Acid Cycle (CAC)
- high ADP & Ca2+ stimulate CAC
- high ATP, GTP, and NADH inhibit CAC
Pyruvate dehydrogenase deficiency
- common form caused by mutation in E1 alpha gene, inherited in X-linked manner
- Other forms autosomal recessive
- results in increased Alanine, Lactate, and Pyruvate blood levels
- chronic lactic acidosis
- treated with thiamine, carnitine, lipoic acids
Pyruvate Carboxylase deficiency
- accumulation of pyruvate, lactic acid, and alanine
- failure to thrive, developmental delays, recurrent seizures, and metabolic acidosis
Glucose 6 Phosphatase deficiency
- autosomal recessive metabolic disease
- glycogen storage disease
- GSD type I or von Gierke disease
- poor tolerance to fasting, growth retardation, hepatomegaly
Effects of Ethanol
- Ethanol metabolism can cause hypoglycemia
- Ethanol dehydrogenase increases NADH to NAD+ ratio
- high NADH opposes gluconeogenesis
- high NADH converts pyruvate to lactate, oxaloacetate to malate (which removes substrates from glycogenic pool)
What is ideal fasting glucose level?
60 - 100 mg/mL
First step of Gluconeogenesis (with pyruvate)
- Pyruvate is converted to oxaloacetate by Pyruvate Carboxylase
- then from Oxaloacetate to Phosphoenolpyruvate (PEP) by PEP Carboxykinase
- Biotin and bicarbonate required (with ATP)
What is the major source of ATP from an overnight fast?
oxidation of fatty acids
What is the rate-limiting enzyme in fatty acid biosynthesis?
-What product does it form?
Acetyl-coA Carboxylase
-Malonyl-coA
What are you likely to find increased levels of in the blood when fasting?
- increased free fatty acids
- increased levels of ketone bodies
What catalyzes the reaction from Fatty Acyl-coA to Acetyl-coA
(CPT-1)
Carnitine palmotyltransferase - 1
What can Fatty Acids be estrified to form?
- Triaglycerols
- Cholesterol Ester
What two substrates are triacylglycerols broken down to form?
- Fatty Acids
- Glycerol
What enzyme catalyzes the conversion of triacylglycerols to fatty acids?
-What stimulates its activity?
HSTL
-epinephrine
What inhibits CPT - 1 ?
Malonyl-coA
Increased Malonyl-coA results in?
- less fatty acid oxidation
- inhibition of CPT - 1
What does an increase in acetyl-coA carboxylase do to ketone bodies?
lowers ketone body production
Effect of excess cholesterol on HMG coA reductase
inhibits it
Effect of excess cholesterol on ACAT
increases it
Effect of excess cholesterol on 7 alpha hydroxylase
increases it
What medication inhibits HMG-coA reductase?
Statins