Metabolism Flashcards
What is metabolism?
A series of chemical reactions in which the product of one reaction is the substrate for the next reaction.
Most important electron carriers
NAD+ and NADP+
Only organ which can synthesize glucose.
Liver (it can also store fat and glycogen)
Minimum fasting blood glucose which must be maintained for proper brain functioning.
60mg/100mL (120g/day)
Final product of glycolysis (aerobic vs anaerobic)
AEROBIC –> pyruvate
ANAEROBIC –> lactate
Glycogenolysis
Break down of glycogen to glucose-1-phosphate and glucose in liver/muscles
Stimulated by epi and glycogen
Glycogenesis
Formation of glycogen from glucose
SGLT1 vs. GLUT2 vs. GLUT4
ALL TRANSPORTERS
SGLT1: sodium glucose transporter. Transports one molecule of glucose or galactose along with two sodium ions.
GLUT2: Insulin independent low affinity. High capacity in liver. Also functions in intestines and kidneys.
GLUT4: Insulin dependent, higher affinity transporter in muscle, heart and adipocytes.
3 main steps of glycolysis
(1) Priming Stage: ATP investment to break down glucose (into glucose-6-phosphatate)
(2) Splitting stage: Fructose-1,6-bisphosphate is converted into 2 glyceraldehyde-3-phasphate molecules.
(3) Oxidoreduction-phosphorylation: ATP earnings (4), NADH creation (2) and pyruvate generation(phosphoenolpyruvate to pyruvate)
3 most important enzymes for glycolysis
(1) Hexokinase/glucokinase
(2) PFK-1
(3) Pyruvate kinase
Used only ONE WAY. For glycolysis and not gluconeogenesis
Hexokinase vs Glucokinase. Important differences, including, which has a higher Km and what does that mean?
Gluco is higher. It is not as easily saturated (not saturated at all at physiological levels of glucose)
HEXO: present in all cell types, inhibited by glucose 6-phosphate, non-inducible (constant)
GLUCO: present in liver and pancreas, inhibited by fructose 6-phosphate, inducible (insulin increases synthesis)
Relationship between PFK-1 and PFK-2
The activity of PFK-1 is regulated by the product of PFK-2, which is fructose-2,6-Biphosphate
Effect of glucagon/epi on PFK-2 and pyruvate kinase in the liver. How does this differ from the skeletal muscle?
LIVER: causes inhibition of PFK-2 (and thus PFK-1) and inhibition of pyruvate kinase
SKELETAL: opposite effect
Regulation of Pyruvate dehydrogenase (PDH)
◦not regulated by glucagon and epi
◦end products inhibit PDH by allosteric inhibition
◦end products cause the phosphorylation and inhibition of PDH (Acetyl CoA and NADH)
Lactate Dehydrogenase A Deficiency (LDHA)
Causes a limited level of NAD+ so these patients cannot maintain moderate levels of exercise due to inability to produce ATP needed for muscle contraction under anaerobic conditions
Net ATP of glycolysis
2 ATP
Galactosemia
Genetic disorder caused by a deficiency of certain enzymes (mainly galactose 1-phosphate uridyltransferase and lactose)
unmetabolized milk sugars build up.
LEADS TO:
Cataracts (cloudiness in the lens), Kidney damage, Liver damage, Jaundice, Brain damage.
TREATMENT: Remove galactose from diet
Hereditary Fructose Intolerance
Causes hypoglycemia, vomiting, jaundice and hepatic failure.
AVOID FOODS HIGH IN FRUCTOSE.
Fates of Pyruvate and the enzymes responsible for each
4 Possible Fates
(1) Alanine (via transamination)
(2) Oxaloacetate (via pyruvate carboxylase)
(3) Lactate (via lactate dehydrogenase)
(4) Acetyl CoA (via pyruvate dehydrogenase)
Insulin promotes the expression of the genes encoding for which glycolytic enzymes?
- Glucokinase
- PFK-1
- Pyruvate Kinase
Cori Cycle
Conversion of lactate to glucose. Lactate comes from muscle and RBC’s.
Requires additional ATP.
Alanine Cycle
Conversion of alanine to glucose. Alanine comes from muscle, usually during severe exercise.
Glucose 6-Phosphatase Function
Needed to convert glycogen into glucose for usage by the body.
kcal/g conversions
carbohydrates: 4 kcal/g
proteins: 4 kcal/g
fat: 9 kcal/g
Ultimate function of insulin
Clear the blood of glucose by any means
Ultimate function of epi
Flood the blood with glucose by any means
Ultimate function of glycogen
Flood the blood with glucose by any means
NAD+ for glycolysis can be regenerated via…
(1) Lactate dehydrogenase
(2) Maltate-aspartate shuttle
(3) Glycerol-phosphate shuttle
The most common form of PDH deficiency is caused by…? What is its inheritance pattern?
Mutations in the E1 alpha gene and is inherited in an X-linked manner.
How many phosphates are generated from the CAC?
10
AA conversion (gluconeogenesis)
Cori Cycle (RBC’s all the time, muscles anaerobically): lactate –> glucose
Alanine cycle (muscles): alanine –> glucose
During an overnight fast, what serves as the major source of ATP?
Oxidation of fatty acids
4 enzymes which are mandatory for glycolysis reversal (glucose formation)
- PEP Carboxykinase
- Pyruvate Carboxylase
- Fructose 1,6-biphosphate
- Glucose 6-phosphatase
Major symptom of glucose 6-phosphatase deficiency
Fatty liver (enlarged)
Effect of ethanol metabolism
Hypoglycemia
Ethanol metabolism increases NADH/NAD ratio. This decreases the formation of pyruvate/oxaloacetate from G3P.
Removes them from the pool for glucogenic mechanisms.
Glucose 6-phosphate dehydrogenase deficiency
G6P Dehydrogenase is the key enzyme in the pentose phosphate pathway.
W/o this enzyme, there is very little formation of` NADPH, which leads to high levels of hydrogen peroxide and eventual cell lysis.
Role of Carnitine. What blocks this?
These are needed to transport fatty acids into the mitochondrial matrix. Without these transporters, fatty acids can’t be used.
Malonyl CoA blocks these Carnitine transporters (CPT1), thereby inhibiting beta-oxidation of fatty acids.
Why can’t the liver use the ketone bodies which it creates
No thiophorase (aka succinyl-CoA Transferase)
Cofactor for Enzymes
Apo-CII: activates lipoprotein lipase (LPL)
Apo-A1: activates (LCAT)
Ligand for Remnant Receptor function
Apo E
Ligand and structural protein for LDL/VLDL receptor
Apo B-100 and B-100
Ligand and structural protein for HDL
Apo A-1 and A-1
Structural protein for chylomicrons
B-48
