essential biochemistry ii.pdflipoprotein function • chylomicrons transport fats from intestines to...
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Lecture Notes for Chapter 17,18,19
Metabolism II
Essential Biochemistry Third Edition
Charlotte W. Pratt | Kathleen Cornely
Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
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Lipid Metabolism
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Approximately half of all deaths in the US are linked to atherosclerosis.
• Atherosclerosis – A slow progressive
disease – Characterized by
hardening of the arteries due to lipid accumulation in blood vessel walls
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Lipids are transported via various lipoproteins.
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Lipoproteins transport cholesterol and other fats.
Small angle neutron scattering of a high-density lipoprotein
HDL: orange Lipid core containing cholesterol, phospholipids, cholesterol esters: green
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Lipoprotein Function • Chylomicrons transport fats from intestines to tissues.
• Very-low-density lipoproteins transport triacylglycerols
from the liver to other tissues.
• Low-density lipoproteins carry cholesterol to the tissues. – LDL levels should be relatively low. – LDL is commonly referred to as “bad cholesterol.”
• High-density lipoproteins export cholesterol from the tissues to the liver. – HDL levels should be relatively high. – HDL is commonly referred to as “good cholesterol.”
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Lipoprotein Function Illustrated
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Lipid Metabolism In Context
• Triacylglycerols contain fatty acids attached to a glycerol backbone.
• Fatty acids are broken down
into 2C and 3C intermediates that feed into the citric acid cycle.
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Triacylglycerols are the primary source of fatty acids.
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Fatty acids are activated before they are degraded.
• Activated fatty acids are acylated to CoA.
• Reaction is
driven by ATP hydrolysis.
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Each round of β oxidation has four reactions.
• Acyl groups are transferred via carnitine.
• Acyl-CoA is degraded into acetyl-CoA.
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β Oxidation is a spiral process.
Let’s look at the reactions of β oxidation
more closely.
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β Oxidation results in ATP production.
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• Formed when glucose is unavailable
• Used to supply some of
the brain’s energy needs
Acetyl-CoA can also form ketone bodies.
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Triacylglycerol synthesis requires a glycerol backbone and fatty acid activation.
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Cholesterol synthesis begins with acetyl-CoA.
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several steps
Squalene more steps
Lanosterol
Cholesterol
19 steps
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Cholesterol can be used in several ways.
• Embedded into membranes • Converted into esters for transport
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Cholesterol can be used in several ways.
• Cholesterol can be a precursor of: – Hormones such as testosterone, estrogen – Bile acids such as cholate
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Cells can synthesize cholesterol as well as take it up from circulating
low-density lipoproteins.
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High-density lipoproteins remove excess cholesterol from cells.
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Amino Acid Metabolism
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Transamination moves amino groups between compounds.
• Transaminase = aminotransferase • A transaminase catalyzes the transfer of an amino group
to an α-keto acid. • Transamination is reversible.
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Nitrogen Metabolism in Context
• Amino acids are synthesized from intermediates of glycolysis and the citric acid cycle.
• Nonessential amino acids can be synthesized.
• Essential amino acids must be obtained from food.
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Amino acids can be classified in terms of their catabolism.
• Glucogenic – giving rise to gluconeogenic precursors – Citric acid cycle intermediates, for example
• Ketogenic – giving rise to acetyl-CoA – Used for ketogenesis or fatty acid synthesis – Not used for gluconeogenesis
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Some amino acids are converted to gluconeogenic substrates via
transamination.
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Some amino acids are converted to gluconeogenic substrates via
transamination.
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Cysteine is converted to pyruvate by a process that releases ammonia
and sulfur.
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Threonine is both glucogenic and ketogenic.
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Approximately 80% of excess nitrogen is excreted as urea.
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Glutamate supplies nitrogen to the urea cycle.
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The starting substrate for the urea cycle is an activated molecule produced by
carbamoyl phosphate synthetase.
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The Urea Cycle
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Amino groups can be disposed of via two routes.
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Integration of Metabolism
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Cellular Locations of Major Metabolic Pathways
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Organs are specialized for different functions.
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The body generates glucose and ketone bodies during starvation.
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Obesity has multiple causes.
• Obesity is impacted by several factors. – Diet – Metabolism – Environmental – Genetic
• The hormone leptin may establish the human
body’s set point weight.
• Distinctions in brown vs. white adipose tissue.
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Diabetes is characterized by hyperglycemia.
• Diabetics excrete large amounts of sugar in their urine.
• Type 1 diabetes is an autoimmune disease.
• In Type 2 diabetes, the body does not
respond to insulin.
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Excess glucose is converted to sorbitol.
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Accumulation of sorbitol in the lens leads to cataract formation.
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The metabolic syndrome links diabetes and obesity.
• Metabolic syndrome can be characterized by high visceral fat.
• High levels of dietary fats can lead to: – Fat accumulation in adipose tissue – Impairment of GLUT4 (transporter)
translocation – Impediment of glucose uptake – Increased gluconeogenesis
• Weight loss improves symptoms of metabolic syndrome.
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