Essential Biochemistry II.pdfLipoprotein Function • Chylomicrons transport fats from intestines to...

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.

Lipid Metabolism

© 2014 John Wiley & Sons, Inc. All rights reserved.

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


Lipids are transported via various lipoproteins.


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


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.”


Lipoprotein Function Illustrated


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.


Triacylglycerols are the primary source of fatty acids.


Fatty acids are activated before they are degraded.

•  Activated fatty acids are acylated to CoA.

•  Reaction is

driven by ATP hydrolysis.


Each round of β oxidation has four reactions.

•  Acyl groups are transferred via carnitine.

•  Acyl-CoA is degraded into acetyl-CoA.


β Oxidation is a spiral process.

Let’s look at the reactions of β oxidation

more closely.


β Oxidation results in ATP production.


•  Formed when glucose is unavailable

•  Used to supply some of

the brain’s energy needs

Acetyl-CoA can also form ketone bodies.


Triacylglycerol synthesis requires a glycerol backbone and fatty acid activation.


Cholesterol synthesis begins with acetyl-CoA.


several steps

Squalene more steps

Lanosterol

Cholesterol

19 steps

Cholesterol can be used in several ways.

•  Embedded into membranes •  Converted into esters for transport


Cholesterol can be used in several ways.

•  Cholesterol can be a precursor of: – Hormones such as testosterone, estrogen – Bile acids such as cholate


Cells can synthesize cholesterol as well as take it up from circulating

low-density lipoproteins.


High-density lipoproteins remove excess cholesterol from cells.


Amino Acid Metabolism


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.


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.



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



Some amino acids are converted to gluconeogenic substrates via

transamination.


Some amino acids are converted to gluconeogenic substrates via

transamination.


Cysteine is converted to pyruvate by a process that releases ammonia

and sulfur.


Threonine is both glucogenic and ketogenic.


Approximately 80% of excess nitrogen is excreted as urea.


Glutamate supplies nitrogen to the urea cycle.


The starting substrate for the urea cycle is an activated molecule produced by

carbamoyl phosphate synthetase.


The Urea Cycle


Amino groups can be disposed of via two routes.


Integration of Metabolism


Cellular Locations of Major Metabolic Pathways


Organs are specialized for different functions.


The body generates glucose and ketone bodies during starvation.


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.


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.


Excess glucose is converted to sorbitol.


Accumulation of sorbitol in the lens leads to cataract formation.


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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Essential Biochemistry II.pdfLipoprotein Function • Chylomicrons transport fats from intestines to...

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