pyruvate metabolism

Question 1

Why is pyruvate metabolism necessary

Answer 1

We live in an environment with lots of O2, and O2 has a high affinity for electrons (thats easily reduced)
Metabolism oxidizes foodstuffs (removal of e) and transfers them to O2, electron storage coenzymes (NAD+, FAD) capture the energy
Proton gradient across mito inner membrane then captures energy gradient and uses it to make ATP

As food is oxidized: alkenes–> alcohols/amine/alkene–> aldehyde/ketone–>COOH and each step releases 2 electrons (each of those need an NAD or FAD)

Question 2

Pyruvate

Answer 2

a critical branch point in mamalian energy metabolism

Glycolytic conversion: provides cell with modest amounts of energy and works even with o2 absent (in ischemia) or limiting (exercise)

Product of pyruvate -> most potential energy becomes 2 NADH getting the most energy out of pyruvate metabolism requires O2, therefore O2 availability can determine the fate of pyruvate

Question 3

The fates of pyruvate

Answer 3

PYRUVATE CAN BECOME:

In CYTO REversible

ALANINE (using alanine transferase + pyroxidil phosphate PLP, and B6)

Lactate (using lactate dehydrogenase) and then go thru cori cycle

IN MITO NON reversible

Oxaloacetate (using pyruvate carboxylase, CO2, and ATP) in liver and kidney

Acetyl CoA (using pyruvate dehydrogenase, NAD (to make NADPH), and Co2) requires cofactors

Question 4

Alanine aminotransferase (ALT)

Answer 4

uses pyroxidil phosphate (PLP) as coenzyme,

Pyruvate–> alanine using L glutamate as amino donor

Muscle wasting during starvation
the proteins are then used for gluconeogenisis

to make the L glutamate need to use NADH–>NAD+
the L alanine goes to liver for gluconeogenisis

pathway is also used during intense exercise

Question 5

Lactate dehydrogenase

Answer 5

pyruvate to lactate

hydride loss of NADH

Question 6

Pyruvate carboxylase

Answer 6

pyruvate-> oxaloacetate -> PEP via malate shuttle

uses biotin as coenzyme
mito, irreversible, abundant in liver and kidney

inhibited by acetyl Co A

Question 7

Pyruvate dehydrogenase complex

Answer 7

Used when high O2 levels in fed state (it makes acetyl CoA aka fat storage)
it couples glycolysis to TCA cycle

Pyruvate + NAD+ + CoA –> acetyl CoA + CO2 + NADH

the PDH complex is activated by high NAD+/NADH, ADP and Ca++

the complex contains 3 enzymes and 5 cofactors:
The Lovely Cofactors For Nerds

Thiamine Pyrophosphate (B1), Lipoic Acid (inhibited by Arsenic), CoA, FAD, NAD+

(T,L, F are catalytic) (C and N are stoichiometric)

The three enzymes are:

1. pyruvate dehydrogenase
2. dihydrolipoyl transacetylase
3. dihidrolipoyl dehydrogenase

Question 8

Pyruvate dehydrogenase Regulation

Answer 8

Inhibitors: high [product], phosphorylation (via kinase)

Fasted state:glucagon activates PDH kinase to inhibit PDH and the subsequent TCA cycle
when insulin is low, fatty acid is released–> B oxidation of fatty acid –> acetyl CoA NADH and ATP–> phosphorylation of PDH kinase

in fed state–> make acetyl CoA
infasted state–> instead of acetyl Co building up fat, you use it for gluconeogenisis by turning off PDH

Question 9

Thiamine and Berberi

Answer 9

Thiamine (B1) deficiency –>Berberi (neuro and cardio dfects) alcoholics have it and get wernikes and korskoffs