Lipid Metabolism PDF

Evolve. Adapt. Overcome. CEFI is now ready. LIPID METABOLISM CHEM 5: BIOCHEMISTRY HAZEL DOROTHY CESAR-VILAN College of Liberal Arts, Sciences and Education  COLLEGE OF LIBERAL AR...

Evolve. Adapt. Overcome. CEFI is now ready. LIPID METABOLISM CHEM 5: BIOCHEMISTRY HAZEL DOROTHY CESAR-VILAN College of Liberal Arts, Sciences and Education  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. LIPIDS Indispensable for cell structure and function Possess a hydrophobic and non-polar nature Differ from rest of the body compounds and unique in their action Constitute about 15-20% of the body weight in humans TAGs – most abundant (85-90%) Stored in the adipose tissue Serve as energy reserve of the body Act as an insulating material for maintaining the body temperature of animals No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. WHY SHOULD FAT BE THE FUEL RESERVE OF THE BODY? TAGs are highly concentrated form of energy. Yielding 9 Cal/g, in contrast to carbohydrates and proteins that produce only 4 Cal/g Fatty acids found in TAGs are in the reduced form TAGs are nonpolar and hydrophobic in nature. Stored in pure form without any association with water Glycogen and proteins are polar, 1 g of glycogen combines with 2 g of water for storage Long chain fatty acids (of fat) are the ideal storage fuel reserves of the body. Fats can support the body’s energy needs for long periods of food deprivation. No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. METABOLIC PROFILE OF ORGANS No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. TRANSPORT OF LIPIDS Insoluble Solubilized in association with proteins à lipoproteins Lipoproteins are transported in the blood stream Free lipids are undetectable in blood No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. DYNAMIC STATE OF BODY LIPIDS Earlier, it was thought The TAGs transported that lipids are inert from intestine and liver storage compounds and are stored in adipose are less significant tissue. metabolically. Body lipids are They are also utilized by continuously being muscle, liver, heart, etc. degraded and as per the needs of the resynthesized. body. Fat stored in the adipose tissue is the fuel reserve of the body. No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. FAT MOBILIZATION Hormone-sensitive TAG lipase – removes the fatty acid either from carbon 1 or 3 of the TAG to form DAG Lipases (specific for DAG and MAG) – cleave the other 2 FAs of TAG Lipolysis – complete degradation of TAGs to glycerol and free acids No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. FAT MOBILIZATION Fate of glycerol: Adipose tissue lacks glycerol kinase Glycerol produced in lipolysis cannot be phosphorylated in the adipose Transported to liver where it is activated to glycerol-3-phosphate May be used for the synthesis of TAGs and phospholipids May also enter glycolysis by getting converted to DHAP Fate of free fatty acids: Enter the circulation and are transported in a bound form to albumin Enter various tissues and are utilized for the energy 95% of energy obtained from fats No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETONE BODIES No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETONE BODIES Water-soluble and energy yielding β-Hydroxybutyrate is not a true ketones since it does not possess a keto group. Acetone is an exception to the group because it cannot be metabolized. No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETOGENESIS Synthesis of ketone bodies Occurs in the liver Enzymes are located in the mitochondrial matrix Precursor: acetyl CoA (formed by oxidation of FAs, pyruvate or some amino acids) No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETOGENESIS Two moles of acetyl CoA condense to form acetoacetyl CoA Catalysed by thiolase, an enzyme involved in the final step of β-oxidation No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETOGENESIS Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β- hydroxy-β-methylglutaryl CoA Catalyzed by HMG CoA synthase, the enzyme which regulates the synthesis of ketone bodies No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETOGENESIS HMG CoA lyase cleaves HMG CoA to produce acetoacetate and acetyl CoA No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETOGENESIS Spontaneous decarboxylation: formation of acetone Reduction by a dehydrogenase: formation of β-hydroxybutyrate No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. UTILIZATION OF KETONE BODIES Water-soluble – easily transported from the liver to various tissues Acetoacetate and β-hydroxybutyrate serve as important sources of energy for the peripheral tissues such as skeletal muscle, cardiac muscle, renal cortex, etc. Tissues which lack mitochondria cannot utilize ketone bodies. Production and utilization is more significant during times of starvation and in cases of diabetes mellitus Major fuel source for the brain and other parts of the CNS during prolonged starvation No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. REACTIONS OF KETONE BODIES Reversal of synthesis: β-hydroxybutyrate is converted to acetoacetate by β-hydroxybutyrate dehydrogenase Acetoacetate is activated to acetoacetyl CoA by thiophorase (succinyl CoA acetoacetate CoA transferase) Thiolase cleaves acetoacetyl CoA to two moles of acetyl CoA Thiophorase is absent in the liver. No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. KETONE BODIES Ketonemia High concentration of ketone bodies in the blood Occurs when the rate of synthesis of ketone bodies exceeds the rate of utilization Predominantly due to increased production of ketone bodies rather than the deficiency in their utilization Ketonuria Excretion of ketone bodies in urine Indication of active fat metabolism Ketosis Overall picture of ketonemia and ketonuria Smell of acetone in breath is a common feature Commonly associated with starvation and severe uncontrolled diabetes mellitus No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. STARVATION Accompanied by increased degradation of fatty acids to meet the energy needs of the body Causes an overproduction of acetyl CoA which cannot be fully handled by the TCA cycle TCA cycle is impaired due to deficiency of oxaloacetate Most of it is diverted for glucose synthesis to meet the essential requirements for tissues like brain Results in an accumulation of acetyl CoA and its diversion for overproduction of ketone bodies No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. DIABETES MELLITUS Associated with insulin deficiency Results in impaired carbohydrate metabolism and increased lipolysis Ultimately leads to the accumulation of acetyl CoA and its conversion to ketone bodies Severe diabetes: Ketone body concentration in blood plasma may reach 100 mg/dL Normal: 1 mg/dL Ketone body urinary excretion may be as high as 500 mg/day Small amounts: 80 mg/dL No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. BIOSYNTHESIS OF FATTY ACIDS No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  COLLEGE OF LIBERAL ARTS, SCIENCES & EDUCATION Calayan Educational Foundation, Inc. FATTY ACID SYNTHESIS Excess carbohydrates and amino acids à FAs à stored as TAGs De novo (new) synthesis of FAs occurs predominantly in liver, kidney, adipose tissue and lactating mammary glands Enzyme machinery for FA production is located in the cytosomal fraction of the cell Acetyl CoA is the source of carbon atoms NADPH provides the reducing equivalents ATP supplies energy for FA formation No part of this material may be reproduced, stored in a retrieval system or transmitted in any form or by any means – electronic, mechanical, photocopying, recording or otherwise, without permission in writing from the author or lecturer.  Evolve. Adapt. Overcome. CEFI is now ready. Thank you for your attention!