metabolism Flashcards
glycogen phosphorylase control
covalent: PKA-> cAMP-> converts ‘b’ to ‘a’
allosteric:
in MUSCLE:
activator=5’AMP
inhibitor=ATP
hexokinase
- present in muscle
- inhibited by G6P
PFK-1
IN MUSCLE: -allosteric inhibitor= ATP and citrate -allosteric activator= AMP IN LIVER: -allosteric activator = F-2,6-Bp (fructose-2,6-bisphosphate) is a potent activator!!!
Pyruvate kinase
-converts PEP to pyruvate (in the direction of glycolysis and opposite direction of gluconeogenesis)
- stimulated by= F-1,6-Bp (like feed-forward)
- inhibited by= ATP
in liver (in addition to the above…) it’s also:
stimulated by PEP
inhibited by alanine (so that biosynthesis can take place instead of glycolysis when energy profile is high!)
glucokinase
- in liver and beta cells of pancreas
- glucose sensor for beta cells
glycogen phosphorylase reaction
- in glycogenolysis
- Glucose to G1P
phosphoglucomutase
- in glycogenolysis: G1P to G6P
- in glycogen synthesis: G6P to G1P
Glucose-6-phosphatase
- converts G6P to glucose
- present in liver and kidney only, as, release of glucose in blood during starvation is needed which is provided by glycogenolysis (liver) and gluconeogenesis (liver and kidney)
Glucose-1-P-uridyltransferase
- In glycogen synthesis
- Glucose-1-Phosphate +UTP—->UDP-Glucose + PPi
Glycogen synthase
UDP-glucose + (glucose)n —–> UDP + (glucose)n+1
protein phosphatase
- glycogen phosphorylase ‘a’ to ‘b’
- inhibited via cAMP pathway
phosphorylase kinase
-glycogen phosphorylase ‘b’ to ‘a’
-activated via cAMP pathway
[in muscle, Ca2+ activates it as well]
pyruvate carboxylase
- pyruvate to oxaloacetate
- uses ATP and biotin (as CO2 carrier)
- generates oxaloacetate for 2 pathways– gluconeogenesis and TCA cycle (‘anaplerosis’)
the only enzyme of gluconeogenesis that’s present in mitochondrial matrix
pyruvate carboxylase
control of pyruvate carboxylase
Allosteric control:
-simulated by–> Acetyl-CoA
PEPCK (PEP carboxykinase)
- converts oxaloacetate to PEP
- uses GTP
- negatively regulated by insulin
hormonal control on the balance between glycolysis and gluconeogenesis in the liver
- control is by regulating the amount of FBP (fructose-1,6-bisphosphate)
- this is done by regulating the phosphorylation of a bifunctional enzyme PFK-2/F-2,6-Bpase
- when glucagon–> PKA active-> phosphorylation of the bifunctional enzyme-> PFK-2 activity decreased and F-2,6-Bpase activity increased-> F-2,6-Bp drops!!–> glycolysis decreases and gluconeogenesis increases
PDH
- multienzyme complex (3 enzymes)
- lipoamide arm
- converts pyruvate to Acetyl CoA
what is the point of no return for glucose-derived carbon?why?
which enzyme controls this point?
Acetyl CoA
as, once the glucose is broken down to acetyl CoA it cannot be converted back to glucose (as acetyl CoA can’t be used for gluconeogenesis)
PDH controls this point
control of PDH activity
(allosteric and covalent modification of PDH; and even allosteric regulation of the covalent modifiers!!!)
allosteric on PDH–> NADH/NAD+ and Acetyl CoA/CoA ratios
PDH kinase phosphorylates and inactivates PDH
PDH phosphatase dephosphorylates and activates PDH
allosteric control on modifiers:
PDH kinase–> inhibited by substrates of PDH (pyruvate); activated by products of PDH (acetyl CoA, etc.)
PDH phosphatase–> activated by Ca (in muscles) and Insulin (in adipocytes)
citrate synthase
-inhibited by ATP
-
What point in TCA cycle is particularly important for regulation during starvation?
- Citrate synthase inhibition by ATP
- because, during starvation the oxaloacetate should be used for gluconeogenesis; ATP is high in liver as its using other fuels and this inhibits the usage of oxaloacetate in TCA cycle in the liver!!
isocitrate dehydrogenase
- inhibited by ‘fed state status’– i.e., when NADH/NAD+ ratio and ATP is high
- stimulated by ADP
alpha-ketoglutarate dehydrogenase
- inhibited by its products (NADH and succinyl CoA)
- stimulated by Ca2+
