L49 – Metabolic features of cardiac tissue Flashcards
(54 cards)
What is used for 60-70% Myocardial ATP production under normal aerobic conditions?
Non-esterified fatty acids (NEFA)
2 sources of Non-esterified fatty acids (NEFA)?
Diet (fatty acids, glucose)
Mobilize stored forms (triacylglycerides in
adipocytes, glycogen in liver and muscle)
How does dietary lipid reach myocardia? Start with dietary lipid in micelles
Dietary lipid (triglycerides (TG)) > micelles > in small intestine (duodenum): pancreatic lipase cleaves TG into fatty acids (FA) + glycerol > enter intestinal cell> reconstitute 2-monoglycerides + FA into TG > coat with phospholipids / lipoprotein > chylomicrons enter blood via lymphatics > heart
How does stored glycogen in liver become mobilized?
In liver: glucose > glycerol-3-phosphate + FA-CoA > TG > coat with lipoprotein to form VLDL > blood
How does stored TAG in adipose tissue become mobilized?
Hormone (e.g. glucagon) activate G protein > adenylate cyclas > cAMP > Protein Kinase A > activate lipase > TG becomes DAG > release FA + glycerol
What 2 ways is FA + glycerol released into blood?
- Lipoprotein
2. Albumin
How does circulating TG enter skeletal/ cardiac muscle?
- breakdown TG into FA + glycerol
2. FA enter muscle through FA translocase
fatty acid translocase (FAT)/CD36 has a preference for which type of Fatty acid?
Long chain fatty acid (LCFA)
What are the 2 enzymes on outer mitochondrial membrane for FA transport?
Acyl-CoA synthase
Carnitine palmitoyl-transferase 1 (CPT1)
Write the reaction catalysed by acyl-CoA synthase.
Fatty acid binding protein (FABP) + CoA + ATP > FABP + fatty acyl-CoA + AMP + PPi
Where does the reaction catalysed by acyl-CoA synthase occur?
Outside of outer mitochondrial membrane
Fatty acyl CoA enters intermembrane space of mitochondria. What is the reaction there?
fatty acyl- CoA + carnitine > fatty acylcarnitine + CoA
Catalyzed by Carnitine Palmitoyl-transferase 1 (CPT1)
Which enzyme is important in regulating whether FA can enter intermembrane space?
Carnitine Palmitoyl-transferase 1 (CPT1)
What is the role of Carnitine?
Carnitine takes over CoA in carrying FA from intermembrane space through inner membrane to mitochondrial matrix
Which two enzymes are found on inner mitochondrial membrane for FA transport?
Carnitine acylcarnitine translocase
Carnitine Palmitoyl-transferase II (CPT2)
What is the reaction of Carnitine Palmitoyl-transferase II (CPT2)? Where does it occur?
Fatty acylcartinine + CoA > fatty acyl CoA + cartinine
Where is fatty acyl CoA found in the membranes of mitchondria?
Outside mitochondria, in intermembrane space (before being converted to fatty acylcartinine and in matrix
Where is fatty acylcartinine found in the membranes of mitochondria?
In intermembrane space and matrix (before being converted to fatty acyl CoA)
What happens to the cartinine in matrix after being detached from fatty acylcartinine?
Carried by cartinine acylcartinine translocase from matrix to intermembrane space
What happens to fatty acyl CoA inside the matrix ?
undergoes β-oxidation to produce:
- FADH2, NADH
- Acetyl-CoA
What is the fate of the acetyl CoA made from the β-oxidation of fatty acyl CoA in mitochondria?
Acetyl-CoA (2-C) combines with
oxaloacetate to form citrate > enter TCA cycle > metabolized into
CO2, H2O, NADH, FADH2
What is the fate of the FADH2, NADH made from the β-oxidation of fatty acyl CoA in mitochondria?
Enter electron transport chain > pump H+
into intermembrane space > H+ goes down concentration gradient to drive ATP synthase > produce ATP
What accounts for the minority 30% of Myocardial ATP production under normal aerobic conditions?
Glucose
What is the fate of glucose used in ATP production in cardiomyocyte?
Enter cardiomyocyte via channel (e.g. GLUT 4) > glycolysis by hexokinase > form pyruvate
> pyruvate catalyzed by PDH to form Acetyl- CoA > TCA cycle > ETC > ATP made
