Lecture Exam 3 Flashcards
What is fatty acid synthase? In the mammalian enzyme, how many active sites does the enzyme have?
-Fatty Acid Synthase: catalyzes assembly of long carbon chains of fatty acids in the cytosol through a repeating four-step sequence
-Seven active sites are in separate domains within a single multifunctional polypeptide chain
What is the general process of fatty acid synthesis? What role does malonyl play?
Addition of two carbons to a growing fatty acyl chain: a four-step sequence.
Each malonyl group and acetyl (or longer acyl) group is activated by a thioester that links it to fatty acid synthase, a multienzyme system.
Condensation of an activated acyl group (an acetyl group from acetyl-CoA is the first acyl group) and two carbons derived from malonyl-CoA, with elimination of CO2 from the malonyl group, extends the acyl chain by two carbons. The mechanism of the first step of this reaction is given to illustrate the role of decarboxylation in facilitating condensation.
The β-keto product of the condensation is then reduced in three more steps nearly identical to the reactions of β oxidation, but in the reverse sequence: the β-keto group is reduced to an alcohol
Elimination of H2O (dehydration) creates a double bond
The double bond is reduced to form the corresponding saturated fatty acyl group
What do elongases and desaturases do?
-Fatty Acid Elongation Systems: lengthen palmitate to form long saturated fatty acids
-Fatty acyl-CoA Desaturase: catalyzes an oxidative reaction that introduces a double bond into a fatty acid chain; is a mixed-function oxidase
What is COX and what molecules does it produce?
-COX: prostaglandin H2 synthase catalyzes the formation of prostaglandin H2 (PGH2)
-COX-1: catalyzes the synthesis of prostaglandins that regulate gastric mucin secretion
-COX-2: catalyzes the synthesis of prostaglandins that mediate pain, inflammation, and fever
What is the general process of triacylglycerol synthesis?
Acyl transferase catalyzes the acylation of the 2 free hydroxyl groups of glycerol 3-phosphate by two molecules of fatty acyl-CoA to yield diacylglycerol 3-phosphate (phosphatidic acid)
Phosphatidic acid phosphatase hydrolyzes phosphatidic acid to form 1,2-diacylglycerol
1,2-diacylglycerol is converted to triacylglycerol by transesterification with a third fatty acyl-CoA
Promoted by insulin
What is the general process of phospholipid synthesis?
Begins with phosphatidic acid or diacylglycerols
Polar head group is attached through a phosphodiester bond (to CDP-diacylglycerol or to hydroxyl of the head group)
What role does HMG-CoA play in cholesterol synthesis? What drugs target this step
-HMG-CoA: is reduced by HMG-CoA reductase to form mevalonate; this is the major regulation point for cholesterol synthesis
-Statins: drug class used to treat patients with elevated serum cholesterol
How is cholesterol synthesis and metabolism regulated?
Covalent modification of HMG-CoA reductase
Transcriptional regulation of HMG-CoA gene
Proteolytic degradation of HMG-CoA reductase
Activation of ACAT, which increases esterification for storage
Transcriptional regulation of the LDL receptor
Insulin and ACAT promote
Glucagon and oxysterol inhibit
How do HDL, LDL, VLDL/IDL, and chylomicrons work in transporting lipids? What are their roles?
-HDL: transports lipids using reverse cholesterol transport
-HDL picks up cholesterol from cholesterol-rich extrahepatic cells and returns it to the liver for unloading
-LDL: carries cholesterol to extrahepatic tissues and macrophages
-VLDL/IDL: lipoproteins that carry cholesterol esters or triacylglycerols from the liver to muscle and adipose tissue
How does cholesterol give rise to steroid hormones?
-Cholesterol undergoes side-chain cleavage in the mitochondria of steroidogenic tissues
-This reaction is catalyzed by mixed-function oxygenases that use NADPH, O2, and mitochondrial P-450
What is nitrogen fixation and nitrogen assimilation? What organisms accomplish this?
-Nitrogen fixation: the conversion of N2 to forms that can support life (NH3, NO2-, NO-)
-Nitrogen Assimilation: a two-step reductive process that bypasses atmospheric N2
-Only bacteria and archaea can fix atmospheric N2 (diazotrophs)
What is glutamine synthetase? What type of inhibition regulates this enzyme?
-There are 3 classes of glutamine synthetase
-GS1(found in bacteria): 12 identical subunits
-GS2 (found in eukaryotes and some bacteria): 10 identical subunits
-GSIII (found in two bacterial species): double-ringed dodecamer of identical chains
-Glutamine synthetases are regulated allosterically, the products work together to provide cumulative feedback inhibition
-Covalent modification helps to increase sensitivity to the allosteric inhibitors
What are some key precursors to amino acid synthesis?
-Carbon skeleton precursors are derived from:
-glycolysis
-the citric acid cycle
-the pentose phosphate pathway
How do essential and nonessential amino acids differ?
Essential amino acids are required in the diet.
Nonessential amino acids are synthesized in the body.
What amino acids serve as a precursor to heme, histamine, and neurotransmitters?
-Heme: glycine
-Histamine: histidine
-Neurotransmitters: tyrosine, histidine, tryptophan
