Mod.A. Bio Lec3 Flashcards
The intracellular form of glucose is
glucose-6-phosphate
Glycolysis (meaning,site,activating hormone)
- معناها :the major oxidative pathway for glucose .
- : المكان in all cells.
- داخل الخلية :found in the cytosol.
- الهرمون المنشط : insulin
Anaerobic Glycolysis
when oxygen is limited (e.g., muscle during intense activity)
OR in certain tissues ( RBCs )
- عدد التفاعلات :
consists of 11 coupled reactions - The last step : is the reduction of pyruvate to lactate by the enzyme lactate dehydrogenase (LDH), and the lactate is transported out of the cell into the circulation.
- ملحوظة هامة جدااا :
The reaction also catalyzes the oxidation of NADH to NAD+; which occurs during the LDH catalyzed reaction. This reduction is required since NAD+ is a necessary substrate for G3PDH, without which glycolysis will cease.
** لذلك :
Importantly, under anaerobic conditions, the regeneration of NAD+ by this step is essential for the continued functioning of glycolysis.( عملية سريعة )
Products of anaerobic glycolysis
2 molecules of lactate + 2 ATP
Products of aerobic glycolysis
2 pyruvate + 8 ATP
3 Glycolysis Reactions are irreversible under physiological conditions:
- hexokinase
- phosphofructokinase
- pyruvate kinase
hexokinase and glucokinase (site, specificity, Km, Activity, Inhibition)
Hexokinase:
site: Most tissues (non-hepatic tissues)
specificity: Any hexose
Km: low
Activity: high
Inhibited by: glucose 6-p (product)
Glucokinase
site:liver
specificity: glucose only
km:high
activity:low
not inhibited by product because liver doesnt use glucose but supplies it to tissues that need it (brain and muscle)
What is the rate limiting enzyme of glycolysis?
Phosphofructokinase
Phosphofructokinase is inhibited by (3)
1- ATP
2-Citrate (ketone bodies and fatty acids)
3- Low pH in the cell (H+) ( no need for excess acidity).
Phosphofructokinase is activated by (2)
1- Fructose-2,6-bisphosphate
2- AMP
Pyruvate Kinase is inhibited by (3)
and how glucagon affects it
ATP, acetyl-CoA and alanine inhibit pyruvate kinase
•Glucagon & cAMP-dependent hormone inhibits pyruvate kinase
phosphorylated form is inactive
Pyruvate Kinase is activated by (1)
Fructose 1,6-bisphosphate activates pyruvate kinase
Gluconeogenesis (def,timing,site)
Definition : is making a new glucose from non-carbohydrate precursors ( Substrates ) .
Timing:
1-fasting (especially after 18 hr due to depletion of liver glycogen )
2- low carbohydrate diet
3- starvation
Organ location: occurs mainly in liver (90%) and
to less extend in renal cortex of kidneys (10%).
Intracellular location: The pathway is partly mitochondrial and partly cytoplasmic
Precursors of gluconeogenesis:
1-Lactate produced in tissues such as the red cell by anaerobic glycolysis and muscles.
2- Glucogenic amino acids derived from muscle proteins (except lysine and leucine).
3- Glycerol released from triglycerides during lipolysis in adipose tissues.
4- Pyruvate
5- all TCA intermediates can be utilized
Can FA synthesize glucose ?
Fatty acids cannot! Why? Acetyl-CoA (through TCA cycle) cannot provide for net synthesis of sugars This is due to the irreversible nature of the pyruvate dehydrogenase reaction, which converts pyruvate to acetyl CoA.
Enzymes involved in Bypass Reaction of Gluconeogenesis (4)
1- Pyruvate carboxylase
2- PEP carboxykinase
3- Fructose 1-6 Biphoshatase
4- Glucose 6-phosphatase
Carboxylation of pyruvate (site,enzyme,cofactors)
mitochondria
Pyruvate Carboxylase
Biotin and ATP
Decarboxylation of oxaloacetate (site,enzyme,cofactors)
cytosol
PEP carboxykinase
GTP
rate limiting enzyme of gluconeogenesis
fructose-1,6-bisphosphatase
How many ATP’s are used in gluconeogenesis ?
6
Cori Cycle (timing, energy efficiency)
لتوقيت : In vigorous skeletal muscle activity
اسم العملية : (Cori cycle).
- Liver & RBCs, type 2B muscle
- Energetically is less efficient
Glucose-alanine cycle (timing, energy efficiency)
التوقيت during fasting, skeletal muscle protein is degraded yielding high amount of alanine
اسم العملية : Glucose-alanine cycle
- Liver & Muscle
- Energetically is more efficient
Physiological significance of gluconeogenesis : 3
1.Maintenance of the blood glucose levels, especially under hypoglycemia conditions
(fasting, starvation, depletion of liver glycogen, and low carbohydrate diet).
- Use of Metabolic waste product from the blood e.g. Glycerol, lactate.
- supply of glucose to anaerobic cells (RBCs) and the brain.
Allosteric regulation of gluconeogenesis: (pyruvate carboxylase, fructose 1-6 biphosphatase)
Pyruvate carboxylase
is allosterically activated (+ve) by excess acetyl CoA produced by excess fatty acid oxidation in the liver during fasting.
Fructose 1-6 Biphosphatase:
is allosterically activated (+ve) by Citrate, ATP and inhibited (-ve) by AMP and F-2,6-bisP.
Hormonal regulation of gluconeogenesis:
1- Insulin:
decreases synthesis of regulatory enzymes of gluconeogenesis
2- Glucagon, Epinephrine, Cortisol
increase synthesis of regulatory enzymes of gluconeogenesis
Glycogen (definition, site)
Glycogen is the principal storage form of carbohydrate in the mammalian body,
* مكانه : present mainly in liver and muscles.
function of glycogen in the liver
is to supply the other tissues via formation of blood glucose.
نظرا ل ( presence of G6Pase )
function of glycogen in the muscles
it serves the needs of muscles only,
حيث أن In the muscle glycogen stores serve as a fuel source for the generation of ATP
. نظرا ل ( absence of G6 Pase )
Glycogenesis (meaning, goal, site, rate limiting enzyme, activating hormone)
Glycogen synthesis
transform glucose to glycogen
In liver: during feeding (high blood glucose)
In muscles: during resting state with abundant energy
Glycogen synthase
Insulin (in liver and muscles)
Glycogenolysis (meaning, goal, site, rate limiting enzyme, activating hormone)
Degradation of glycogen
Transform glycogen to glucose
Liver: during fasting (low blood glucose)
Muscles: during rapidly contracting state, stress
Glycogen phosphorylase
Glucagon in the liver (in case of fasting)
Epinephrine in liver AND MUSCLES *** (in case of stress)
GS is allosterically regulated by
1- activated by glucose-6-P
2- deactivated by phosphorylation , feedback inhibition by glycogen itself
GP is allosterically regulated by
1- activated by AMP and by phosphorylation
2- inhibited by ATP, G-6-P and caffeine
Hormonal regulation of glycogen by insulin
Secreted by pancreas in hyperglycemia.
- Stimulates Glycogenesis.
Hormonal regulation of glycogen by glucagon
- Secreted by pancreas in response to hypoglycemia.
- Stimulates glycogen breakdown in liver via cAMP active GP
- Acts primarily in liver
( لا يعمل في muscle )
Hormonal regulation of glycogen by epinephrine
Secreted by adrenal gland.
- Increases muscle glycolysis and release of glucose from the liver.
- Stimulates glycogen breakdown through : cyclic AMP → activate PKA → phosphorylate
1- GP [from (b) form to (a) form (active form)].
2- GS (from (a) form to (b) form (inactive form)].
Ca2+-calmodulin complex :
ncreases immediately the glycogenolysis rate by activation of phosphorylase (GP) even in the absence of epinephrine action.
– Ca2+ plays as second messenger in this mechanism.
How AMP affects glycogenolysis
activates 1- phosphorylase, enhancing glycogenolysis.
2- phosphofructokinase-1 (PFK-1). Stimulating the utilization of glucose
through glycolysis for energy production.
Von Gierke’s disease (cause and result)
Deficiency of glucose-6-phosphatase of the liver
1- Fasting hypoglycemia,
2-glycogen deposition in liver cirrhosis
3-Accumulated glucose-6-P is diverted to HMP, result in increased purines catabolized to uric acid → hyperuricemia
Cori’s disease:
Deficiency of debranching enzyme
Glycogen accumulates in liver ( hepatomegaly)
Anderson’s disease
Deficiency of branching enzyme
•Abnormal Glycogen accumulates •Cardiac or liver failure may cause death in the 1st year of life.
Mc Ardle’s Disease (Type V):
Deficiency of muscle phosphorylase enzyme
Muscle cramps , damage ( inadequate energy supply)
