lipid metabolism II Flashcards
what lipases are involved in the breakdown of TAGs
ATGL - adipose triglyceride lipase
hormone sensitive lipase (HSL)
lipoprotin lipase (LPL)
monoacylglycerol lipase (MAG Lipase)
transport of Fatty Acids:
short chain fatty acids ____
long chain complexed with ____ for transport
soluble
albumin
breakdown of TAGs
fat cell:
TAG → ____ and ____ ____
liver cell:
glycerol → ____ → ____
glycerol → ____ → ____
other tissue:
fatty acids → ____ ____ ____ → ____ ____ → TCA cycle
fat cell:
glycerol and fatty acids
liver cell:
glycolysis → pyruvate
gluconeogenesis → glucose
other tissues:
fatty acid oxidation → acetyl CoA
activation of HSL is modulated by ____
phosphorylation
____ and ____ are 2 major signals that promote mobilization of TAGs
hunger and exercise
major controllers of HSL signaling in hunger and exercise:
____ (secreted in response to hunger)
____ (secreted in resopnse to exercise)
both of these phosphorylate HSL (activate it) and promote ____ in ____
glucagon
epinephrine
lipolysis in adipocytes
mechanisms of regulation of HSL:
____ status signal inhibits mobilization of TAGs
____ (secreted in resopnse to high carb meal)
____ HSL (via activation of protein phosphatase I) to inhibit lipolysis
fed
insulin
dephosphorylates
perilipin:
- family of proteins that coat ____ ____ in ____ and muscle cells
- regulate ____ by controlling physical access to ____ (lipid breakdown enzyme)
- perilipins regulated by ____ (phosphorylation allows association with HSL) which promotes lipolysis
- overexpression of Perilipin I ____ lipolysis
- target of ____ treatment
- lipid droplets adipocytes
- lipolysis HSL
- PKA
- inhibits
- obesity
fatty acid breakdownA: an overview:
phase I:
phase II:
phase I: activation and transport to mitochondiral matrix
phase II: beta oxidation
TAGs → diacylglycerol (via ____ ) → monoacylglycerol (via ____ ) → glycerol (via ____ )
HSL
lipoprotein lipase
MAG
activators of HSL:
inhibitors of HSL:
glucagon, epinephrine, norepinephrine,
insulin
mobilization of FAs from Adipocytes: hunger and exercise
- glucagon and/or epinephrine bind to ____
- ____ is formed
- cAMP activates ____
- PKA phosphorylates ____ and ___
- glucagon and epinephrine also release another activator that activates ____
- GPCR
- cAMP
- PKA
- perilipin and HSL
- ATGL
mobilization of FAs from Adipocytes: Fed
- ____ binds to RTK (receptor tyrosin kinase)
- RTK activates ____
- protein phosphatase 1 (PP1) dephosphorylates and inactivates ____
- insulin
- protein phosphatase 1
- HSL
phase I FA breakdown:
- as long-chain FA-albumin complex crosses the plasma membrane, it loses ____
- outer mitochondrial membrnae is not permeable to ____ FAs
- must first be combined with ____ to make fatty acyl CoA in cytosol
- fatty acyl CoA has now crossed the outer mitochondrial membrane and is present in the ____ space
- fatty acyl CoA cannot cross ____ mitochondrial membrane
- ____ must be added which replaces CoA
- ____ is now permeable across the inner mitochondrial membrane
- once in the mitochondrial matrix, ____ is replaced with ____ to form fatty acyl CoA
- fatty acyl CoA becomes substrate for ____
- albumin
- free
- CoA
- intermembrane
- inner
- carnitine
- fatty acyl carnitine
- carnatine CoA
- beta-oxidation
translocation to mitochondrial matrix:
- carnitine → acyl carnitine via ____ ____ ____
- acylecarnitine translocates across inner mitochondrial membrane via ____
- acyl carnitine → carnitine via ____ ____ ____
- carnitine acyltransferase I
- translocase
- carnitine acyltransferase II
carnitine acyltransferase I is the rate limiting enzyme of
carnitine acyltransferase I is inhibitied by
fatty acid degradation
malonyl CoA
enzymes in phase I:
- fatty acyl CoA synthetase:
- located on the ____ ____ ____
- activates long chain FAs using ____
- forms a ____ bond between FAs and CoA to form fatty acid CoA
- carnitine palmityltransferase I (CPT-1) (also - carnitine acyltransferase)
- located in ____ ____
- transfers fatty acyl from fatty acid CoA to ____
- forms FA - ____
- rate-limiting enzyme in ____ ____
- inhibited by ____
- carnitine-acylcarnitine translocase
- antiporter: ____ (in) ⇔ ____ (out)
- carnitine palmitoyltransferase II
- transfers Fatty acyl from FA-carnitine to ____
- forms FA - ____
- fatty acid CoA is now in the ____
- fatty acyl CoA synthetase
- outer mitochondrial membrane
- ATP
- thioester
- carnitine palmityltransferase I (CPT-1)
- intermembrane space
- carnitine
- carnitine
- FA degradation
- malonyl CoA
- carnitine-acylcarnitine translocase
- FA-carnitine carnitine
- carnitine palmitoyltransferase II
- CoA
- CoA
- mitochondrial matrix
4 steps phase II: beta-oxidation:
- 4.
- oxidation: acyl CoA Dehydrogenase (ACAD)
- FADH2 which enters ETC to form 2 ATP
- hydration:
- oxidation:
- NADH which enters ETC to form 3 ATP
- thiolysis:
- releases Acytl CoA that enters into TCA cycle
four main steps of beta-oxidation generate:
FADH2 (via acyl CoA dehydrogenase - ACAD) (1st oxidation step)
NADH (via 2nd oxidation step)
Acetyl CoA (via thiolysis) enters TCA cycle
calculation of ATP released from beta-oxidation of palmitic acid:
FADH2 :
NADH :
Acetyle CoA:
Total:
ATP used:
Net ATP:
FADH2: 7 x 2 = 14 ATP
NADH: 7 x 3 = 21 ATP
Acetyl CoA: 8 x 12 = 96 ATP
Total: 131 ATP
ATP used: 2
Net ATP: 129 ATP
ketone bodies are ____ - soluble and ____ compounds
water
acidic
3 types of ketone bodies
acetoacetate
beta-hydroxybutyrate
acetone
ketone bodies:
are produced only in ____
provide energy for ____ tissues and ____ during fasting and starvation
liver
peripheral
brain
formation of ketone bodies:
- 2 molecules of ____ combine to make ____
- a third molecule of ____ is added to acetoacetyl CoA to form ____
- 3-hydroxy-3-methyl-glutaryl CoA breaks down and releases CoA to form ____ which then goes on to form other ketone bodies
- acetyl CoA acetoacetyl CoA
- acetyla CoA 3-hydroxy-3-methyl-glutaryl CoA
- acetoacetate
utilization of Acetoacetate:
- other ketone bodies can break down to form ____
- acetoacetate → acetoacetyl CoA (via ____ )
- acetoacetyl CoA → 2 Acetyl CoA (via ____ ) which can enter TCA cycle
- acetoacetate
- CoA transferase
- thiolase
what conditions favor production of ketone bodies
fasting and starvation
(no glucose, not undergoing glycolysis) (relying on FA degradation)
first few hours of fasting:
energy source is blood glucose, followed by glycogen stored in muscle and liver
next gluconeogenesis in liver (synthesis of new glucose)
after 1 day of fasting:
energy source is TAGs stored in adipose tissue
TAGs broken down to release FFA which undergo Beta oxidation
after 3 days of fasting:
ketone bodies are made in liver and proteins in muscles are broken down
glycerol from TAGs and glucogenic amino acids from proteins enter gluconeogenesis
supply energy to brain and RBCs
after 1-2 weeks of starvation:
brain switches to ketone bodies as major energy source
after 2-3 months of starvation:
TAGs are depleted, proteins are main source
coma and death
diabetic ketoacidosis (DKA):
- glucose cannot enter ____ or ____ cells
- when glucose is not being utilized, the ____ is shut down
- free fatty acids are released and broken down via beta-oxidation to ____
- excess acetyl CoA leads to production of ____ ____
- since ketone bodies are acidic, blood pH ____
- ____ and ____ can result
- fat or liver
- TCA
- acetyl CoA
- ketone bodies
- drops
- coma and death
physiological ketosis
mild to moderate increase in ketone bodies
occurs in fasting, during pregenancy, after prolonged exercise and ketogenic diet
pathological ketoacidosis:
- occurs when glucagon/insulin ratio is increased, favoring FA breakdown
- increased aceyl CoA in hepatic mitochondria
- increased gluconeogenesis - reduced oxaloacetate
- increased ketone bodies
- acetone exhaled via breath, friuty odor in individuals with uncontrolled diabetes
