METABOLIC CHANGES IN FASTING AND STARVATION Flashcards
WHAT ARE THE 2 MAIN THINGS THE BODY NEEDS TO DO DURING FASTING/STARVATION AND WHY:
1) SPARE GLUCOSE:
- TO CONSERVE IT FOR TISSUES OR CELLS THAT HAVE AN ABSOLUTE OR NEAR ABSOLUTE REQUIREMENT FOR IT, DONE BY SWITCHING FUEL UTILIZATION FROM GLUCOSE TO FATTY ACIDS
2) SYNTHESIZE NEW GLUCOSE:
- DONE USING NON-CARBOHYDRATE SUBSTRATES
- DONE THROUGH GLUCONEOGENESIS
IN WHICH ORGAN ARE THE FATTY ACIDS OXIDIZED TO KETONE BODIES?
IN THE LIVER
WHERE CAN GLUCONEOGENESIS OCCUR?
MAINLY IN THE LIVER, BUT TO SOME EXTENT IN THE KIDNEYS TOO
WHICH NON CARBOHYDRATE SUBSTRATES CAN BE USED TO FORM GLUCOSE IN GLUCOENEOGENESIS AND HOW DOES THE BODY GET THEM?
LACTATE (FROM ANAEROBIC GLYCOLYSIS)
AMINO ACIDS (FROM PROTEOLYSIS MOSTLY IN MUSCLES)
GLYCEROL (RELEASED WITH FATTY ACIDS FROM ADIPOSE TISSUE DUE TO INCREASED LIPOLYSIS CAUSED BY THE DECREASE IN THE INSULIN/GLUCAGON RATIO THAT ACCOMPANIES STARVATION)
WHAT CHANGE IN THE INSULIN/GLUCAGON RATIO ACCOMPANIES STARVATION?
THE RATIO IS DECREASED;
WHAT ARE CHYLOMICRONS?
LIPOPROTEINS (CONTAIN TRIGLYCERIDES) WHICH ARE SECRETED INTO THE LYMPHATIC SYSTEM OF THE SMALL INTESTINE
WHICH ENZYME HYDROLYSES THE TRIGLYCERIDES WITHIN CHYLOMICRONS (I.E. DEGRADES CIRCULATING TRIGLYCERIDES IN THE BLOODSTREAM)?
LIPOPROTEIN LIPASE
WHAT CAN HAPPEN WITH FATTY ACIDS ONCE THEY ARE RELEASED FROM THE TRIGLYCERIDES BY THE LIPOPROTEIN LIPASE?
A) THEY CAN BE USED FOR OXIDATION AND ATP FORMATION
B) THEY CAN BE USED IN ADIPOSE TISSUE FOR THE RE-SYNTHESIS AND STORAGE OF TRIGLYCERIDES
WHAT IS THE PRODUCT OF FATTY ACID OXIDATION IN THE MITOCHONDRIA?
ACETYL CoA
WHAT HAPPENS TO REMNANTS OF CHYLOMICRONS ONCE THE LIPOPROTEIN LIPASE HAS RELEASED FATTY ACIDS?
THEY ARE CLEARED BY THE LIVER AND THE TRIGLYCERIDES LEFT IN THEM ARE USED TO GENERATE FATTY ACIDS WITHIN THE LIVER AND RE-EXPORT THEM IN LIVER’S OWN VERSION; VLDL
WHAT DOES THE LIVER SYTNHESISE USING REMNANTS OF CHYLOMICRONS AND THE TRIGLYCERIDES THAT REMAINED IN THEM?
VLDL (VERY LOW DENSITY LIPOPROTEIN)
GIVEN THAT FATTY ACIDS ARE HYDROPHOBIC AND INSOLUBLE IN THE BLOOD PLASMA, THEY NEED TO BE BOUND BY A CARRIER PROTEIN. WHAT IS THE NAME OF THAT PROTEIN?
ALBUMIN
ARE FATTY ACIDS SOLUBLE IN BLOOD PLASMA?
NO
HOW ARE CHYLOMICRONS AND VLDL HELPFUL TO ALBUMIN?
CAPACITY OF ALBUMIN TO BIND FATTY ACIDS IS LIMITED SO ITS USEFUL TO HAVE THOSE LIPOPROTEINS AS LIPID CARRIERS BETWEEN TISSUES
WHAT IS THE STRUCTURE OF A LIPOPROTEIN MOLECULE?
THE HYDROPHOBIC CORE OF THE MOLECULE (E.G. TRIGLYCERIDES, CHOLESTEROL ESTERS) IS SHELTERED BY A SHELL OF POLAR, WATER-COMPATIBLE MOLECULES (E.G. PHOSPHOLIPIDS AND CHOLESTEROL)
WHAT DOES THE TERM ‘APOPROTEIN’ REFER TO?
THE PROTEIN PORTION OF A MOLECULE OR COMPLEX CONSISTING OF A PROTEIN MOLECULE JOINED TO A NONPROTEIN MOLECULE OR MOLECULES
WHICH APOPROTEIN DO CHYLOMICRONS AND VLDL CONTAIN AND WHAT DOES IT DO?
APOB; IT WRAPS ITSELF AROUND LIPID COMPONENTS OF THOSE LIPOPROTEINS AND ‘STITCHES’ THEM TOGETHER
WHERE DOES PROTEOLYSIS MOSTLY OCCUR?
IN MUSCLES
WHY IS HDL CONSIDERED THE ‘GOOD’ CHOLESTEROL CONTAINING PARTICLE?
BECAUSE IT TAKES CHOLESTEROL FROM TISSUES AND RETURNS IT TO THE LIVER, WHERE IT CAN BE EXCRETED IN BILE
GLUCOSE CAN BE SYNTHESIZED FROM FATTY ACIDS OR LIPIDS CAN BE SYNTHESIZED FROM GLUCOSE, WHICH ONE IS TRUE?
LIPIDS CAN BE SYNTHESIZED FROM GLUCOSE
DO THE SYNTHESIS AND OXIDATION OF FATTY ACIDS OCCUR SIMULTANEOUSLY? HOW IS THIS REGULATED?
THEY DO NOT OCCUR SIMULTANEOUSLY
THIS IS ACHIEVED THROUGH THE FIRST METABOLITE IN THE FATTY ACID SYNTHESIS (MALONYL-CoA) ACTING INHIBITORY TOWARDS THE FIRST ENZYME THAT ALLOWS FATTY ACIDS INTO THE MITOCHONDRIA WHERE THEY ARE OXIDIZED (CPT1 ENZYME)
WHICH METABOLITE FORMED FROM GLUCOSE IS USED TO SYNTHESISE FATTY ACIDS?
ACETYL-CoA
WHERE IN THE CELL DOES THE SYNTHESIS OF FATTY ACIDS OCCUR?
IN THE CYTOPLASM
WHERE DOES BETA OXIDATION OCCUR?
IN THE MITOCHONDRIAL MATRIX
WHAT IS THE NAME OF THE FIRST ENZYME THAT NEEDS TO ALLOW FATTY ACIDS TO ENTER THE MITOCHONDRIA FOR THEIR OXIDATION?
CARNITINE PALMITOYLTRANSFERASE (CPT1)
WHAT IS THE 1ST METABOLITE IN THE FATTY ACIDS SYNTHESIS PATHWAY?
MALONYL-CoA
WHAT IS STEATOSIS?
ABNORMALLY HIGH BUILD UP OF FAT IN THE LIVER
WHAT IS THE PURPOSE IN INCREASED LIPOLYSIS IN WHITE ADIPOSE TISSUE DURING STARVATION?
- RELEASE OF FATTY ACIDS THAT WILL BE USED BY MUSCLES IN PREFERENCE TO GLUCOSE
- PROVIDING FATTY ACIDS FOR OXIDATION WITHIN LIVER TO FORM KETONE BODIES WHICH THE BRAIN WILL BE ABLE TO USE
WHAT IS MALONYL-CoA MADE FROM?
GLUCOSE
HOW DOES GLUCOSE UTILIZATION INHIBIT FATTY ACID OXIDATION IN THE FED STATE?
BECAUSE GLUCOSE UTILIZATION LEADS TO RAISE IN MALONYL-CoA (WHICH IS MADE FROM GLUCOSE). MALONYL-CoA IS THE FIRST METABOLITE OF FATTY ACID SYNTHESIS AND A POTENT INHIBITOR OF CPT1 ENZYME, WHICH IS CRUCIAL FOR TRANSFER OF FATTY ACIDS INTO MITOCHONDRIAL MATRIX WHERE THEY WOULD BE OXIIDIZED. GIVEN THAT CPT1 IS BLOCKED, FATTY ACIDS CANNOT BE OXIDIZED UNNECESSARILY
HOW DO FATTY ACIDS INHIBIT GLUCOSE UTILIZATION IN E.G. MUSCLE DURING STARVATION (I.E. WHEN THEY BECOME THE MAIN SOURCE OF ENERGY)?
- THE HIGH RATE OF FATTY ACID OXIDATION RAISES ACETYL-CoA LEVELS AND INHIBITS PYRUVATE DEHYDROGENASE; THUS STOPPING PYRUVATE FROM BEING OXIDIZED (SO THE OXIDATION FORMED FROM GLUCOSE IS STOPPED)
- SOME OF THE CITRATE PRODUCED FROM ACETYL-CoA (WHICH IS MOSTLY USED FOR ATP SYNTHESIS) WILL BE RELEASED INTO THE CYTOSOL WHERE IT WIL INHIBIT THE SECOND REACTION OF GLYCOLYSIS CATALYZED BY PHOSPHOFRUCTOKINASE 1 (PFK1)
WHAT HAPPENS TO INSULIN CONCENTRATION DURING FASTING?
THEY ARE DECREASED
WHAT ARE SOME OF THE MECHANISMS THAT ENSURE THAT COMPETITION BETWEEN GLUCOSE AND FATTY ACID UTILIZATION BY MUSCLE IS MINIMISED?
- HIGH RATES OF GLUCOSE LEAD TO PRODUCTION OF MALONYL-CoA WHICH IS RELATED TO LIPOGENESIS AND INHIBITS FATTY ACIDS OXIDATION
- WHEN GLUCOSE LEVELS ARE LOW AND FATTY ACIDS OXIDIZED AT HIGH RATES, THE ACETLY-CoA WHICH IS PRODUCED INHIBITS PYRUVATE-HYDROGENASE SO THE PYRUVATE GOTTEN FROM GLYCOLYSIS CANNOT BE OXIDIZED
- CITRATE THAT IS PRODUCED FROM ACETYL-CoA IS PARTIALLY RELEASED IN THE CYTOSOL WHERE IT WILL BLOCK THE PFK1 ENZYME AND BLOCK THE 2ND STEP OF GLYCOLYSIS
WHAT ARE THE GLUCAGON LEVELS LIKE DURING FASTING?
HIGH
WHAT ARE THE SUBSTRATES FOR GLUCONEOGENESIS AND WHERE DO THEY COME FROM?
GLYCEROL; ADIPOSE TISSUE
AMINO ACIDS AND LACTATE; MUSCLE
WHEN ARE THE AMINO ACIDS FORMED IN MUSCLE?
FOLLOWING THE LOSS OF ANTI-PROTEOLYTIC ACTION OF INSULIN
WHICH STEPS IN GLYCOLYSIS NEED TO BE BYPASSED WHEN THE LIVER IS TRYING TO CREATE GLUCOSE? (THEY CANNOT BE REVERSED BECAUSE THEY HAVE HIGH ENERGY CHANGES ASSOCIATED WITH THEM)
- GLUCOSE TO G-6-P (CATALYSED BY HEXOKINASE)
- FRUCTOSE-6-P TO FRUCTOSE-1,6-bP (PHOSPHOFRUCTOKINASE 1)
- PEP TO PYRUVATE (PYRUVATE KINASE)
WHAT IS GLUCOKINASE?
A TYPE OF HEXOKINASE EXPRESSED IN HEPATOCYTES
WHICH ENZYME IS USED TO BYPASS THE FUNCTION OF GLUCOKINASE (HEXOKINASE) DURING GLUCONEOGENESIS?
GLUCOSE-6-PHOSPHATASE
WHERE IN THE CELL IS GLUCOKINASE EXPRESSED AND WHERE IS GLUCOSE-6-PHOSPHATASE EXPRESSED?
1) CYTOSOL
2) ENDOPLASMIC RETICULUM
WHICH FORM DO FATTY ACIDS NEED TO BE IN TO ENTER THE MITOCHONDRIA AND WHICH ENZYME FACILITATES THIS?
ACYLCARNITINE ESTERS, CPT1
WHICH ENZYME IS USED TO REVERSE THE STEP IN GLYCOLYSIS CATALYSED BY PFK1?
FRUCTOSE 1,6-BIPHOSPHATASE (FbPase)
WHAT EFFECTS DOES THE METABOLITE FRUCTOSE-2,6-BISPHOSPHATE (F2,6bP) HAS ON ENZYMES PFK1 AND F16bPASE?
ACTIVATES PFK1 (AND GLYCOLYSIS) INHIBITS F16bPase (AND GLUCONEOGENESIS)
HOW IS F2,6bP FORMED?
FROM F-6-PHOSPHATE THROUGH PFK2
PFK2 IS REGULATED BY WHICH HORMONE?
GLUCAGON
HOW MANY CARBONS DOES PYRUVATE HAVE?
3
WHICH HORMONE INHIBITS THE ENZYME PYRUVATE KINASE (I.E. STOPS CONVERSION OF PEP TO PYRUVATE)?
GLUCAGON
ENZYME RESPONSIBLE FOR PEP TO PYRUVATE CONVERSION?
PYRUVATE KINASE
WHAT DOES INSULIN DO TO ACETYL CoA CARBOXYLASE, MALONYL CoA LEVELS AND PFK2 AND WHICH EFFECTS DOES THIS HAVE?
- ACTIVATES ACETLY CoA CARBOXYLASE
- INCREASES MALONYL CoA LEVELS (INHIBITS FATTY ACIDS OXIDATION REQUIRED TO SUPPORT GLUCONEOGENESIS)
- ACTIVATES PFK2 (WHICH INCREASES F2,6bP LEVELS, ACTIVATES GLYCOLYSIS AND INHIBITS GLUCONEOGENESIS)
ROLE OF ACETYL CoA CARBOXYLASE:
COVERTING ACETLY CoA TO MALONYL CoA
WHERE CAN KETO BODY FORMATION OCCUR?
MAINLY IN THE LIVER + MINOR EXTENT IN THE KIDNEY
HOW LONG ARE THE LONG CHAIN FATTY ACIDS?
MORE THAN 14 CARBON ATOMS
TWO MOST COMMON LONG CHAIN FATTY ACIDS AND THEIR NUMBER OF CARBONS?
PALMITIC, 16C
OLEATE, 18 C
WHICH TRANSPORTER IS INVOLVED WITH FATTY ACID ENTRY INTO THE CELL?
CD 36 (cluster of differentiation 36)
FATTY ACIDS ARE LET INTO CELLS BY CD 36,
THEN THEY ARE CONVERTED TO CoA ESTERS AND THEN TO ACYLCARNITINE ESTERS BY CPT1 TO BE ABLE TO CROSS THE MITOCHONDRIAL MEMBRANE.
THEN THEY NEED TO BE CONVERTED BACK TO ACYL CoABEFORE SERVING AS SUBSTRATES FOR BETA OXIDATION? WHICH ENZYME IS RESPONSIBLE FOR THIS LAST CONVERSION?
CPT2
WHERE IS CPT2 LOCATED IN THE CELL?
INNER MITOCHONDRIAL MEMBRANE FACING THE MATRIX
HOW MANY CARBON ATOMS ARE SPLIT OFF THE FATTY ACID CHAIN AT EACH TURN OF BETA OXIDATION CYCLE TO GIVE RISE TO 1 ACETYL CoA?
2
WHAT IS GENERATED DURING BETA OXIDATION EXCEPT FOR ACETYL CoA?
FADH2 AND NADH
ATP PRODUCED THROUGH BETA OXIDATION IS USED TO SUPPORT WHICH REACTION?
GLUCONEOGENESIS
HOW ARE THE HIGH ENERGY ELECTRON CARRIERS WHICH ARE OXIDIZED IN THE ELECTRON TRANSPORTER CHAIN TO CREATE ATP CREATED THROUGH BETA OXIDATION?
BREAKDOWN OF FATTY ACIDS INTO 2 CARBON SEGMENTS CREATING ACETYL CoA GENERATES FADH2 AND NADH AT EVERY TURN OF THE CYCLE
+ THE ACETYL CoA THAT IS PRODUCED CAN GO THROUGH THE CITRIC ACID CYCLE TO PRODUCE MORE OF THE FADH2 AND NADH
DO BETA OXIDATION AND GLUCONEOGENESIS OCCUR AT THE SAME TIME?
YES, BOTH STIMULATED BY GLUCAGON, BETA OXIDATION CONTINUOUSLY PRODUCES ENERGY NEEDED TO DRIVE GLUCONEOGENESIS
ARE KETONE BODIES WATER OR FAT SOLUBLE?
WATER SOLUBLE
WHICH ORGANS APART FROM THE BRAIN CAN USE KETONE BODIES?
SKELETAL MUSCLE AND HEART
CAN LIVER USED KETONE BODIES?
NO
WHAT IS DEAMINATION?
SAFE REMOVAL OF AMINO GROUP FROM (NITROGEN ATOM) FROM THE AMINO ACID SO THE CARBON SKELETON CAN BE USED FOR GLUCONEOGENESIS OF KETOGENESIS
CAN AMINO ACIDS BE METABOLISED TO ANYTHING APART FROM GLUCOSE?
ACETLY CoA (CONTRIBUTE TOWARDS KETOGENESIS)
APART FROM STARVATION WHEN INSULIN IS DECREASED, IN WHICH SITUATIONS CAN PROTEOLYSIS BE INCREASED?
WHEN INSULIN COUNTER-REGULATORY HORMONES ARE INCREASED IN CASE OF E.G. STRESS OR TRAUMA AND WITH HEAVY EXERCISE AND MUSCLE INJURY
IN WHICH FORM IS NITROGEN EXCRETED IN MAMMALS?
AS UREA
2 MOST COMMONLY USED KETOACIDS IN STARVATION?
PYRUVATE WHICH GIVER RISE TO ALANINE WHICH CAN DIRECTLY BE USED IN THE LIVER FOR GLUCONEOGENESIS
ALPHA-KETOGLUTARATE WHICH GIVES RISE TO GLUTAMATE (ALPHA-KETOG. IS AN INTERMEDIATE OF THE TCA CYCLE)
WHICH ORGAN IS THE MAJOR SITE OF UREAGENESIS?
THE LIVER
GLUTAMATE IS CONVERTED TO GLUTAMINE WHERE?
IN THE MUSCLE
HOW MANY BRANCHED CHAIN AMINO ACIDS ARE THERE AND WHAT ARE THEIR NAMES?
3; LEUCINE, ISOLEUCINE, VALINE
WHAT DOES IT MEAN IF AN AMINO ACID IS KETOGENIC VS GLUCOGENIC?
KETOGENIC; GIVES RISE TO ACETYL CoA
GLUCOGENIS; GIVES RISE TO INTERMEDIATES OF THE TCA
WHAT IS THE MAIN AIM OF STARVATION METABOLISM?
RETAINING BRAIN FUNCTION IN THE FACE OF A COMPLETE CESSATION OF GLUCOSE INPUT FROM THE DIET
DOES STARVATION METABOLISM HAS CATABOLIC OR ANABOLIC PROFILE?
CATABOLIC
