Review Cards Flashcards
Name differences in Hexokinase and Glucokinase (location, affinity, regulators)
Rxn: Glucose –> G-6-P
Glucokinase: in liver, low affinity, high Km for glucose
- Glucose –> cytosol
- F-6-P –> nucleus
- Insulin –> increase expression (inducible)
Hexokinase: outside liver, high affinity, low Km for glucose
- G-6-P negative feedback
- Non-inducible, constitutive
What is the main activator of PFK-1?
F-2,6-bisP allosteric activator
Reaction: PFK-1: F-6-P –> F-1,6,-P
Other activators: AMP, ADP
Inhibitors: ATP, Citrate
How is PFK-2 differentially regulated in liver and muscle under fasting?
Liver: PFK-2 kinase domain is phosphorylated by glucagon/Epi –> inhibited –> no F-2,6-bisP –> inhibit hepatic glycolysis
Muscle: PFK-2 phosphatase domain is phosphorylated by Epi, so kinase is active –> increased F-2,6-bisP –> activate PFK-1 –> glycolysis active
What are the regulators of Pyruvate Kinase?
[Reaction: PEP –> Pyruvate]
Activated by insulin (de-phosphorylation) and F-1,6-bisP (feed forward)
Inhibited by glucago/Epi (phosphorylation), ATP, Alanine
What are the 4 fates of Pyruvate?
- Transamination –> Alanine
- Pyruvate Carboxylase –> Oxaloacetate
- LDH –> Lactate
- PDH –> Acetyl CoA
What are the names of the 2 shuttles that regenerate NAD+?
- Malate-Aspartate
- Glycerol-Phosphate
Use them to regenerate NAD+ in the mitochondria because NADH can’t cross the membrane; they can be reoxidized by ETC, so get a lot more ATP from this than making lactate
What is the reaction catalyzed by LDH? What is the point? How is it different in skeletal and heart muscle?
Pyruvate + NADH+ –> Lactate + NAD+
- To regenerate NAD+
- Skeletal m. will convert Pyruvate –> Lactate (2 ATP)
- Heart m. will convert Lactate –> Pyruvate for TCA
What is catalyzed by PDH? How is it regulated?
Pyruvate + CoASH + NAD+ –> Acetyl CoA + NADH
- Needs vitamin cofactors
- Acetyl CoA, NADH are feedback inhibitors
What is Galactosemia?
Deficiency of Galactose-1-P-Uridyltransferase –> accumulation of galactose –> increase of galactitol –> cataracts, jaundice, enlarged liver, kidney damage, brain damage
What are the 3 sources of Acetyl CoA?
- Glycogen –> Glucose –> Pyruvate –> Acetyl CoA
- TAGs –> FFA –> Acetyl CoA
- Proteins –> a.a. –> Acetyl CoA
What are the 3 fates of Acetyl CoA?
- TCA
- Ketone bodies
- Sterols, FAs
How many ATP are made with each cycle of TCA?
9 ATP + 1 GTP = 10 ATP
What does isocitrate dehydrogenase control? How is it regulated?
Fine control of TCA
Reaction: [isocitrate –> a-ketoglutarate]
Activated by: ADP
Inhibited by: ATP, NADH
What does a-ketoglutarate dehydrogenase control? How is it regulated?
Fine control of TCA
Reaction: [a-ketoglutarate –> succinyl coA]
Activated by: ADP, Ca2+
Inhibited by: ATP, GTP, NADH, Succinyl coA
What are the non-carbohydrate precursors used to make glucose in Gng?
Pyruvate, Lactate, Glycerol, Glucogenic a.a.
What is the first step of gluconeogenesis? Enzyme? Reaction? Regulation?
Pyruvate –> Oxaloacetate
- Enzyme: Pyruvate Carboxylase
- Requires ATP, Biotin cofactor
- Activated by Acetyl CoA
Where are GLUT-2 and GLUT-4 receptors located? What are their differences?
GLUT-2 is insulin-independent ([glucose]-mediated) and is on hepatocytes
GLUT-4 is insulin-dependent and is in skeletal muscle
How is Glycogen Phosphorylase regulated?
(draw)
How is Glycogen Synthase regulated?
(draw)
What is the rate limiting enzyme of the PPP? What is the effect of its deficiency?
Glucose-6-Phosphate Dehydrogenase
- Hemolytic Anemia (oxidative stress on RBCs)
- Protective against Malaria (b/c pathogen needs NADPH)
What is the rate limiting enzyme of FA biosynthesis? How is it regulated?
[Acetyl CoA –> Malonyl CoA]
Catalyzed by Acetyl CoA Carboxylase
Activated by: low fat diet, insulin, citrate
Inhibited by: Palmitoyl-CoA, Glucagon/Epi
What does HSTL do? How is it regulated?
HSTL: [TAGs –> FA + Glycerol]
Activated by Epi/Glucagon, ACTH
Inhibited by Insulin
What is the rate-limiting enzyme of Fatty Acid B-oxidation? What is its regulator?
CPT-1: brings FA into mitochondrial matrix
[FA –> Acetyl CoA] via [Carnitine –> acylcarnitine]
- Inhibited by Malonyl-CoA (product of Acetyl-CoA Carboxylase), so you don’t want to make ketone bodies if you are making FA (don’t use what you’re making)
What pathway is HMG-CoA Synthase involved in? Where is it located?
Ketone body formation [Acetoacetate –> HMG CoA]
Liver mitochondria
