Bioenergetics Flashcards
What are some characteristics of the TCA cycle?
A biochemical hub of the intermediary metabolism
Oxidizing carbon fuels for harvesting high energy e-
It is amphibolic and a source of precursors of biosynthesis
Takes place inside mitochondria
Acetyl CoA is the activated form of what?
Acetate
What are the three energy nutrients that acetyl CoA is obtained from?
Carbs, lipids and proteins
How is acetyl CoA obtained from carbs?
Glucose –> oxidation –> 2 pyruvate –> 2 acetyl CoA
How is acetyl CoA obtained from lipids?
TAG –> FAs –> acetyl CoA (beta oxidation)
Oxidation of KBs –> acetyl CoA
How is acetyl CoA obtained from proteins?
Breakdown into various amino acids –> acetyl CoA
Which form of PDC is active and what enzyme activates it?
Dephosphorylated form which is catalyzed by pyruvate dehydrogenase phosphatase (PDP)
Which form of PDC is inactive and which enzyme inactivates it?
Phosphorylated form which is catalyzed by pyruvate dehydrogenase kinase (PDK)
What three enzymes made up the pyruvate dehydrogenase complex (PDC)?
E1 (pyruvate decarboxylase), E2 (dihydrolipoyl transacetylase) and E3 (dihydrolipoyl dehydrogenase) which are all derived from vitamin B derivatives
What are the 5 coenzymes needed by PDC?
Thiamine pyrophosphate (TPP), lipoic acid, FAD, CoA and NAD+
Which 3 conenzymes of PDC act as prosthetic groups and are permanently bound to PDC?
TPP, lipoic acid and FAD
Which 2 coenzymes of PDC act as co-substrates and associate with PDC temporarily?
CoA and NAD+
Which vitamin is TPP derived from?
B1 (thiamine)
Which vitamin is CoA derived from?
B5 (pantothenic acid) (PENTothenic acid)
Which vitamin is lipoic acid derived from?
None
Which vitamin is FAD derived from?
Vitamin B2 (riboflavin)
Which vitamin is NAD+ derived from?
Vitamin B3 (niacin)
List factors that activate PDC activity
Its substrates and low energy signals (elevated [NAD] and [ADP])
High insulin concentrations in adipose
Ca2+ and Mg2+ via allosteric activation
ADP, CoA, NAD and pyruvate via inhibition of PDK
List factors that inhibit PDC activity
Its end products and high energy signals (elevated NADH and ATP)
Fasting conditions where acetyl CoA and NADH are high due to oxidation of FAs via activation of PDK
Arsenite by binding to lipoic acid in E2
What reaction is catalyzed by PDC?
Pyruvate + NAD + CoA –> Acetyl CoA + CO2 + NADH + H+
What occurs in a phosphatase deficiency?
PDC is always in its phosphorylated inactive form
Glucose made into lactate instead of acetyl CoA resulting in lactic acidosis (high lactatic acid in the blood)
CNS is mostly affected
Alanine intake should be restricted due to pyruvate accumulation and a ketogenic diet may be recommended
Describe how PDC is affected in the tissues
Ca released during muscle contraction activates PDC
Cardiac muscle Ca may inhibit PDK thus activating PDC
PDP is a Mg dependent enzyme and in adipose tissue insulin may activate the enzyme by lowering the Km for Mg
Describe pyruvate dehydrogenase deficiency (neonatal lactic acidosis)
May be due to PDC defects specifically in E1 (TPP)
Males more affected bc gene for E1 is on the X chromo
Pts will have high serum pyruvate and lactate
Tx: vitamin B1 (replaces deficient E1 subunit), lipoic acid (stimulates activity of PDC), or biotin (metabolizes pyruvate by the alternate enzyme pyruvate carboxylase)
Dicholoracetate (inhibits PDK) or ketogenic diet may also be suggested
How does arsenite (derived from aresenic) affect lipoic acid?
Arsenite irreversibly binds to two SH groups on lipoic acid subunit (E2) and limits its availability
This affects PDC, alpha-KG dehydrogenase and branched chain keto acid dehydrogenase which rely on lipoic acid
What is Beriberi?
Vitamin B1 (thiamine) deficiency (no TPP)
sx: weight loss, SOB, mental confusion, speech difficulties, pain, etc
tx: thiamine supplements along with water soluble vitamins
Leads to increased levels of pyruvate and alpha KG in the blood due to impaired action of PDC and alpha KG dehydrogenase which need TPP
Wet vs Dry Beriberi
Dry form involves peripheral neuropathy
Wet form affects cardiovascular function
Wenicke-Korsakoff syndrome
Form of vitamin B1 deficiency/Beriberi in alcoholics
Describe steps 1 and 2 of the TCA cycle
Condensation of Acetyl CoA and OAA to form citrate catalyzed by citrate synthase
Citrate then isomerized to isocitrate by aconitase