Biochem 406

• In intestinal epithelial cells, free fatty acids are 


  bound to fatty acyl binding proteins
• which of the following statements is true? 1) humans store most of their energy as glycogen. 2) glycogen binds about 2g of water per gram of carbohydrate 3) the energy content of glycogen and fat are equal 4) glycogen is more reduced than fat.

  glycogen binds about 2g of water per gram of carbohydrate
• biochemical intermediates can be used in different pathways for multiple purposes
• anabolic and catabolic pathways can be regulated by hormones such as glucagon and insulin
• control of enzyme levels through the regulation of gene expression is one example of long-term regulation of a metabolic pathway
• human pancreatic lipase (HPL) requires a protein called colipase for activity
• Bile salts help emulsify dietary fats in the intestine
• What is true about human fatty acid synthase (FAS)


  it has a flexible phosphopantetheine arm covalently attached to the Acyl-Carrier Protein domain of the FAS
• The NADPH used in the reductive steps of fatty acid biosynthesis comes from: 


  NADPH is generated as citrate and is converted to pyruvate in the cytosol and the conversation of glucose-6-P to ribulose-5-P in the pentose phosphate pathway.
• Linoleate and alpha-linoleate are "essential fatty acids" because ___


  humans cannot synthesize alpha-linoleate and linoleate; which are required precursors for the synthesis of other important long-chain fatty acids.
• what is the committed step in fatty acid synthesis (FAS)?


  the formation of malonyl-CoA
• Phosphatidic Acid is an intermediate in the synthesis of both fats and phospholipids
• Glycerol-P can be synthesized from either Dihydroxyacetone Phosphate or from Glycerol
• Both Acyl-CoA synthase and Acyl-transferase are required for the synthesis of Phosphatidic Acid
• Which lipoprotein participates in reverse cholesterol transport?


  HDL
• What is true about fatty acid synthesis and degradation?

  Under the conditions in which they occur in cells, both fatty acid synthesis and degradation are exergonic processes.
• Glucagon binding to its receptor produces cAMP by activating adenylate cyclas
• GLucagon binds to a GPCR on the plasma membrane
• Glucagon binding to it's receptor eventually activates Protein Kinase A (PKA)
• Why is this statement wrong: Glucagon is a small molecule released from pancreatic Beta-cells in response to low blood glucose levels?

  Alpha cells NOT Beta cells!
• Lipoprotein particles that transport dietary fats are synthesized in intestinal epithelial cells
• option 1 with cis double bond in the middle

  
• What are the observed responses to glucagon?

  -activation of hormone sensitive lipase

  -activation of ATGL (adipose triglyceride lipase)

  -phosphorylation of perilipins on the surface of lipid droplets
• which metabolite is the substrate for the enzyme catalyzing the committed step in cholesterol biosynthesis?

  Beta-hydroxy-Beta-methylglutaryl-CoA
• Assembly of Acetyl-CoA carboxylase (ACC) into long filaments increases activity
• what happens to ketone bodies after they are synthesized?

  they are exported to other tissues to be used for fuel
• what are observed responses to insulin?

  -enhanced storage of fatty acids as triglycerides

  -activation of Acetyl-CoA carboxylase

  -dephosphorylation of Acetyl-CoA carboxylase
• Cholesterol is stored as cholesterol esters in lipid droplets
• high concentrations of cholesterol in tissues lead to:

  • decreased expression of the gene for HMG-CoA reductase
  • decreased expression of the gene for the LDL receptor
  • Activation of Acyl-CoA Cholesterol Acyltransferase (ACAT)
• Cholesterol is released from LDL particles when they are degraded in the lysosome during the uptake of cholesterol by extra-hepatic tissues
• High circulating levels of cholesterol :

  • can be caused by a. genetic mutation that reduces the number of functional LDL receptors on the surface of cells
  • can be treated with drugs that block dietary absorption of cholesterol
  • can result in atherosclerosis
  • can be treated with satin drugs
• in the regulation of cholesterol synthesis:

  • glucagon stimulates phosphorylation of both HMG-CoA reductase and Acetyl-CoA carboxylase
  • two different proteases working sequentially in the Golgi membrane release the bHLH domain (a transcriptional activator) from SREBP
  • when cholesterol levels are high, a complex formed with INSIG in the ER membrane promotes the degradation of the HMG-CoA reductase
• A common signal that is covalently attached to a protein to mark it for destruction by the Proteasome is:

  covalent modification by K48-linked poly-ubiquitin chains
• The highly acidic milieu of the stomach helps to unfold proteins for enzymatic degradation
• Lysosomes:

  • lysosomal enzymes include Lipase, Amylases, Proteases, and nucleases
  • The concentration of H+ inside the lysosome is ~100x higher than in the cytosol
  • Lysosomes provide the only known way for the cell to degrade large cellular structures
  • Lysosomal V-type ATPases create the low pH inside lysosomes by using ATP
• Proteasome:

  • The Beta-subunits of the core particle contain threonine protease activity
  • The 19S Regulatory Particle has a AAA ATPase that is needed to unfold proteins and thread them into the 20S core particle
  • The 20S Proteasome Core Particle is made up of four ring structures, with each ring containing 7 subunits
• Ubiquitin:

  • Ubiquitin is an 8.5 kDa protein with 76 AAs
  • The AA sequence of Ubiquitin is highly conserved among different eukaryotes
  • The very C-terminus of Ubiquitin features 2 glycine residues that are important for conjugation to substrate proteins
  • The 7 lysine residues and the N-terminus of Ubiquitin can be modified with other molecules of Ubiquitin to build poly-ubiquitin chains
• The glucose-alanine cycle involves

  • the transport of pyruvate from muscle to liver in the form of alanine
  • the transport of NH4+ from muscle to liver in the form of alanine
• the reaction of the urea cycle converts ammonia to urea
• What strategies are used to treat urea cycle disorders?

  -supplement diet with arginine

  -supplement with molecules like Benzoate that promote metabolic reactions that utilize ammonia